Interesting article on Achillion HCV pipeline from currinBioteh.com contributor Jason Chew. Read the original article here: http://seekingalpha.com/article/244145-what-s-next-for-achillion-pharma
Achillion stock (ACHN) has been flat all year, underperforming the biotech indices as well as its peers in the Hepatitis C drug development community. The stock began to leap a couple days after the company announced that data from ongoing clinical studies of ACH-1625 has been accepted for presentation at the 21st Annual Conference of the Asian Pacific Association for the Study of the Liver (APASL 2011) to be held February 17-21, 2011. It has since climbed from $2.73 to close at $4.00 Wednesday, a 47% increase since the December 6th announcement.
So why all the excitement? Achillion had been making headlines all year; it promoted two new drugs into the clinic, began Phase II trials for lead candidate ACH-1625, presented at multiple industry conferences, and raised a total of $71.4 million in stock offerings.
The reason, I believe, is a key phrasing in the press release, “data from ongoing clinical studies of ACH-1625” was to be presented at the conference. There is only one ongoing study: A 144 patient Phase IIa randomized, double blinded trial of ACH-1625 in combination with ribavirin and peg-interferon alpha. The trial begins with a dose-ranging 28 day phase that will be evaluated to determine the optimal dose for the final 12 week treatment phase.
The company had initially targeted March 2011 for release of the first set of results. Having the ability to move the release date up to February speaks well for trial enrollment. This data will provide the first look at how Achillion’s lead candidate performs in a larger setting and importantly, in combination with current standard of care. ACH-1625 has already been shown to significantly reduce viral loads in patients by 3 to 4.25 log10 and maintain a sustained viral response even after therapy has stopped. It has also been shown to be safe up to 2000mg/day, a level far above the highest dose tested in this Phase IIa.
Pre-clinical studies show ACH-1625 to be additive-synergistic to ribavirin and peg-interferon alpha; this study will be a first look at how well those studies translate in the clinic. Although 28 days is still short, the multiple active drug doses as well as a placebo control will allow investigators to gauge in detail the effectiveness of ACH-1625 in this combination. In any case, a full profile of the compound and its potential as part of this three-drug regimen will be in known by the end of 2011. There’s a lot riding on this study.
Aside from its lead compound, Achillion also has a lineup of several other HCV antivirals in development. The once promising ACH-1095, an inhibitor of the NS4A protease is in Phase I. It was originally developed in collaboration with Gilead (GILD), but its rights have since been handed back to the company- though Gilead still retains the ability to opt in at a later stage in the compound’s development.
Early this year in January, a second NS3 protease inhibitor, ACH-2684, was nominated to enter clinical development. It's interesting that Achillion is developing additional NS3 inhibitors considering there are so many out there. This one is being positioned as more potent and effective against commonly seen viral mutants. It will enter Phase I trials in 2011.
The NS5A inhibitor, ACH-2928, was nominated in mid-year. It is also set to initiate Phase I testing in 2011. ACH-2928 is one of the few NS5A inhibitors currently in development. The most prominent competitor compound is BMS-790052 from Bristol Myers Squibb (BMY), currently in Phase II and looking pretty good. Both of these compounds have similarly high potencies in vitro.
Achillion also has some work in antibiotics and HBV, but they are not a major focus. The goal now is to push forward with its HCV pipeline. 2011 will be pivotal for the company as data comes in from its lead project. Funds raised during the year will allow it to complete both portions of the Phase II trial and at the same time initiate two separate Phase I studies. It will be interesting to see how the company chooses to proceed from there.
Thursday, December 30, 2010
Wednesday, December 29, 2010
Scripps scientists identify new target to inhibit replication of Hepatitis C virus....
Scientists have discovered a molecular interaction between a structural hepatitis C virus protein (HCV) and a protein critical to viral replication.
This new finding by researchers from the Florida campus of The Scripps Research Institute strongly suggests a novel method of inhibiting the production of the virus and a potential new therapeutic target for hepatitis C drug development.
These new data underline the essential role of the viral protein known as 'core' as a primary organizer of the infectious HCV particle assembly and support a new molecular understanding of the formation of the viral particle itself.
"While our finding that the HCV core interacts with the non-structural helicase protein was not totally unexpected, this had not really been confirmed until this study," said Donny Strosberg, who led the study.
"But the most exciting part is that small molecule inhibitors of dimerization [the joining of two identical subunits] of core actually inhibit interaction between core and helicase, thus possibly preventing production of an infectious viral particle," said Strosberg.
Previously, Strosberg developed a novel quantitative test for monitoring these protein-protein interactions with the specific goal of identifying inhibitors of the core dimerization, which would block virus production.
However, in the new study, Strosberg and colleagues focused on non-structural proteins that provide functions relating to HCV production, in particular NS3 helicase.
The scientists' findings have supported a growing body of evidence that this protein participates in the assembly and production of infectious viral particles.
The interaction of the core protein with this non-structural protein also confirms core as a key organizer of virus assembly and suggests it acts to facilitate the packaging and integration of the newly synthesized viral RNA.
The findings were published in the Journal of General Virology. (ANI)
This new finding by researchers from the Florida campus of The Scripps Research Institute strongly suggests a novel method of inhibiting the production of the virus and a potential new therapeutic target for hepatitis C drug development.
These new data underline the essential role of the viral protein known as 'core' as a primary organizer of the infectious HCV particle assembly and support a new molecular understanding of the formation of the viral particle itself.
"While our finding that the HCV core interacts with the non-structural helicase protein was not totally unexpected, this had not really been confirmed until this study," said Donny Strosberg, who led the study.
"But the most exciting part is that small molecule inhibitors of dimerization [the joining of two identical subunits] of core actually inhibit interaction between core and helicase, thus possibly preventing production of an infectious viral particle," said Strosberg.
Previously, Strosberg developed a novel quantitative test for monitoring these protein-protein interactions with the specific goal of identifying inhibitors of the core dimerization, which would block virus production.
However, in the new study, Strosberg and colleagues focused on non-structural proteins that provide functions relating to HCV production, in particular NS3 helicase.
The scientists' findings have supported a growing body of evidence that this protein participates in the assembly and production of infectious viral particles.
The interaction of the core protein with this non-structural protein also confirms core as a key organizer of virus assembly and suggests it acts to facilitate the packaging and integration of the newly synthesized viral RNA.
The findings were published in the Journal of General Virology. (ANI)
Tuesday, December 21, 2010
Vertex Ends Part of Telaprevir Combination Drug Study for Hepatitis C
The cause of this discontinuation of the Q12h TVR + VX-222 without peg and riba was viral breakthrough. Peg and ribavirin isn't going anywhere soon.
Vertex Pharmaceuticals Inc. discontinued one part of a clinical study evaluating its hepatitis C treatments.
Vertex is halting a test of its medicine telaprevir in combination with its other experimental therapy called VX-222, the Cambridge, Massachusetts-based company said in a statement. Vertex will continue testing telaprevir and VX-222 in groups of patients who will receive it with one or two drugs given as a combination treatment. The study is the second of three phases of clinical tests typically required for U.S. approval.
Telaprevir, which Vertex is developing with Johnson & Johnson of New Brunswick, New Jersey, is the company’s most advanced experimental drug. There are no medicines available for hepatitis C patients who don’t respond to standard drugs. Howard Liang, an analyst at Leerink Swann & Co. in Boston, estimated telaprevir may generate $2.6 billion annually by 2013.
“This trial has provided important information regarding telaprevir and VX-222-based combination regimens, and three of the five treatment arms are proceeding as planned,” Robert Kauffman, Vertex’s chief medical officer, said in the statement.
Hepatitis C often persists as a chronic condition that causes nausea, weakness and exhaustion as it destroys the liver. It affects about 4 million Americans and 200 million people worldwide, according to the National Institutes of Health.
Vertex ended another two-drug arm of the study in October.
Vertex fell 1.1 percent at 5:06 p.m. New York time in extended trading after gaining 76 cents, or 2.1 percent, to $36.32 at the close of the Nasdaq Stock Market.
To contact the reporter on this story: David Olmos in San Francisco at dolmos@bloomberg.net
To contact the editor responsible for this story: Reg Gale at Rgale5@bloomberg.net
Vertex Pharmaceuticals Inc. discontinued one part of a clinical study evaluating its hepatitis C treatments.
Vertex is halting a test of its medicine telaprevir in combination with its other experimental therapy called VX-222, the Cambridge, Massachusetts-based company said in a statement. Vertex will continue testing telaprevir and VX-222 in groups of patients who will receive it with one or two drugs given as a combination treatment. The study is the second of three phases of clinical tests typically required for U.S. approval.
Telaprevir, which Vertex is developing with Johnson & Johnson of New Brunswick, New Jersey, is the company’s most advanced experimental drug. There are no medicines available for hepatitis C patients who don’t respond to standard drugs. Howard Liang, an analyst at Leerink Swann & Co. in Boston, estimated telaprevir may generate $2.6 billion annually by 2013.
“This trial has provided important information regarding telaprevir and VX-222-based combination regimens, and three of the five treatment arms are proceeding as planned,” Robert Kauffman, Vertex’s chief medical officer, said in the statement.
Hepatitis C often persists as a chronic condition that causes nausea, weakness and exhaustion as it destroys the liver. It affects about 4 million Americans and 200 million people worldwide, according to the National Institutes of Health.
Vertex ended another two-drug arm of the study in October.
Vertex fell 1.1 percent at 5:06 p.m. New York time in extended trading after gaining 76 cents, or 2.1 percent, to $36.32 at the close of the Nasdaq Stock Market.
To contact the reporter on this story: David Olmos in San Francisco at dolmos@bloomberg.net
To contact the editor responsible for this story: Reg Gale at Rgale5@bloomberg.net
Monday, December 20, 2010
Janssen Seeks European Marketing Authorization For Investigational Hepatitis C Treatment Telaprevir
It will be interesting to see how Tibotec supports Telaprevir in Europe, with a possible competitor, TMC435 waiting in the wings. Vertex, with it's relatively rich, advanced pipeline in HCV, esp with the relatively drug-interaction free HCV non-nuc VX-222 that would be a nice complementary acquisition for the J&J family. According to outside sources, Merck only expects a 35% marketshare for Boceprevir vs Telaprevir. Given the potential baggage that comes along with Telaprevir with Q8h dosing, highly variable PK at q12h and the potential severity of the rash, esp in people of color, Merck (for once) may be underestimating the market potential of Boceprevir - Chris
Janssen-Cilag International NV announced the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for telaprevir, an investigational, oral, direct-acting antiviral for the treatment of chronic genotype 1 hepatitis C virus (HCV), the most common form of the virus. Telaprevir is a potent and selective protease inhibitor (PI), which when combined with pegylated-interferon and ribavirin (the current treatment standard), shows activity in patients that are new to treatment and who have been previously treated but were not cured, including partial responders, relapsers and those who have had little or no response (null responders) to the current standard of treatment.
The EMA has accepted telaprevir for accelerated assessment, which is granted to quicken access to innovative, new medicines of major public-health interest. Tibotec BVBA, a global research and development company with specific experience in virology, is developing telaprevir in collaboration with Vertex Pharmaceuticals. Tibotec BVBA is an affiliate company of Janssen.
"The EMA submission for telaprevir is a landmark in the treatment of HCV and demonstrates our dedication to addressing unmet medical needs by developing innovative treatments for infectious diseases," said Johan Van Hoof, Global Therapeutic Area Head Infectious Diseases and Vaccines at Janssen. "Above all, it is an important step towards making telaprevir available to people living with HCV."
It is estimated that 170 million people are living with HCV around the world, including more than five million in Europe. Chronic HCV can result in serious long-term health problems, and an estimated 30 percent of patients will develop progressive liver disease, including cirrhosis (damage and scarring of the liver), which places them at risk for liver insufficiency and liver cancer. HCV is the most common cause of liver transplant in Europe.
The current standard of care for HCV genotype 1 patients, pegylated-interferon and ribavirin, is administered for 48 weeks and only 40 to 50 percent of genotype 1 patients achieve a sustained virologic response (SVR), defined as achieving undetectable levels of the virus in the blood for six months after completion of treatment, and considered an indicator of cure. Re-treatment with pegylated-interferon and ribavirin in patients who have previously failed this treatment shows only limited success. ,
The EMA submission is supported by results from three phase 3 studies, which compared telaprevir in combination with the current standard of treatment to the current standard of treatment alone in HCV genotype 1 patients. Results were very positive:
- Significantly higher SVR rates were observed in treatment-naïve patients treated with telaprevir compared to the current standard treatment of pegylated-interferon and ribavirin (75 percent vs. 44 percent)
- The majority of patients were cured by week 24, which is half the duration of therapy with the current standard of treatment8,
- There was a three-fold increase in cure rates (65 percent vs. 17 percent) across all types of previously treated patients who were given telaprevir compared to the current treatment standard, including prior null responders (31 percent vs. 5 percent) 10
- The most common adverse events in the telaprevir-based treatment groups were fatigue, pruritus, nausea, headache, anemia, rash, influenza-like illness, insomnia, fever and diarrhea. The majority of these adverse events were mild to moderate.8,9,10
"Current treatment for hepatitis is lengthy and only effective for approximately half of treatment-naïve patients, and even fewer patients who failed previous treatment," commented Stefan Zeuzem, Professor of Medicine and Chief, department of medicine, J W Goethe University Hospital, Frankfurt. "If approved, telaprevir would help to significantly improve cure rates and shorten treatment duration for many people living with HCV, compared to current standard treatment."
About the Telaprevir Development Program
To date, more than 2,500 people with HCV genotype 1 have received telaprevir-based therapy (telaprevir combined with the current standard of treatment) as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE trials.8,9,10 The telaprevir clinical development program is the largest conducted to date for any investigational direct-acting antiviral hepatitis C therapy.
- ADVANCE evaluated telaprevir-based regimens in approximately 1,088 treatment-naïve patients with chronic HCV infection. Data from the ADVANCE trial were presented at the 2010 American Association for the Study of Liver Diseases (AASLD) annual meeting in November 2010.8
- ILLUMINATE evaluated the benefits of extending telaprevir-based therapy in 540 treatment-naïve patients whose HCV was undetectable at weeks 4 and 12 of treatment. 322 of these patients were randomized to receive 24 or 48 weeks of treatment, and it was found that there was no benefit to extending treatment to 48 weeks. Data from the ILLUMINATE meeting were presented at AASLD in November 2010.9
- REALIZE evaluated telaprevir-based regimens in approximately 650 treatment-failure HCV patients. Data from the REALIZE trial will likely be published in 2011.
Telaprevir is being developed by Tibotec BVBA, an affiliate company of Janssen, in collaboration with Vertex Pharmaceuticals and Mitsubishi Tanabe Pharma for the treatment of genotype 1 HCV in combination with pegylated-interferon and ribavirin in both patients who have failed prior treatment and those who have never been treated. Tibotec BVBA has the commercialisation rights for telaprevir in Europe, Latin America, the Middle East, Africa, India, Australia and New Zealand, pending approval by the respective regulatory authorities. Vertex will commercialise telaprevir in the U.S., Canada and Mexico and Mitsubishi Tanabe Pharma has rights to commercialise telaprevir in Japan and certain Far East countries.
About Tibotec BVBA
Tibotec BVBA is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and HCV drugs, and anti-infectives for diseases of high unmet medical need.
Janssen-Cilag International NV announced the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for telaprevir, an investigational, oral, direct-acting antiviral for the treatment of chronic genotype 1 hepatitis C virus (HCV), the most common form of the virus. Telaprevir is a potent and selective protease inhibitor (PI), which when combined with pegylated-interferon and ribavirin (the current treatment standard), shows activity in patients that are new to treatment and who have been previously treated but were not cured, including partial responders, relapsers and those who have had little or no response (null responders) to the current standard of treatment.
The EMA has accepted telaprevir for accelerated assessment, which is granted to quicken access to innovative, new medicines of major public-health interest. Tibotec BVBA, a global research and development company with specific experience in virology, is developing telaprevir in collaboration with Vertex Pharmaceuticals. Tibotec BVBA is an affiliate company of Janssen.
"The EMA submission for telaprevir is a landmark in the treatment of HCV and demonstrates our dedication to addressing unmet medical needs by developing innovative treatments for infectious diseases," said Johan Van Hoof, Global Therapeutic Area Head Infectious Diseases and Vaccines at Janssen. "Above all, it is an important step towards making telaprevir available to people living with HCV."
It is estimated that 170 million people are living with HCV around the world, including more than five million in Europe. Chronic HCV can result in serious long-term health problems, and an estimated 30 percent of patients will develop progressive liver disease, including cirrhosis (damage and scarring of the liver), which places them at risk for liver insufficiency and liver cancer. HCV is the most common cause of liver transplant in Europe.
The current standard of care for HCV genotype 1 patients, pegylated-interferon and ribavirin, is administered for 48 weeks and only 40 to 50 percent of genotype 1 patients achieve a sustained virologic response (SVR), defined as achieving undetectable levels of the virus in the blood for six months after completion of treatment, and considered an indicator of cure. Re-treatment with pegylated-interferon and ribavirin in patients who have previously failed this treatment shows only limited success. ,
The EMA submission is supported by results from three phase 3 studies, which compared telaprevir in combination with the current standard of treatment to the current standard of treatment alone in HCV genotype 1 patients. Results were very positive:
- Significantly higher SVR rates were observed in treatment-naïve patients treated with telaprevir compared to the current standard treatment of pegylated-interferon and ribavirin (75 percent vs. 44 percent)
- The majority of patients were cured by week 24, which is half the duration of therapy with the current standard of treatment8,
- There was a three-fold increase in cure rates (65 percent vs. 17 percent) across all types of previously treated patients who were given telaprevir compared to the current treatment standard, including prior null responders (31 percent vs. 5 percent) 10
- The most common adverse events in the telaprevir-based treatment groups were fatigue, pruritus, nausea, headache, anemia, rash, influenza-like illness, insomnia, fever and diarrhea. The majority of these adverse events were mild to moderate.8,9,10
"Current treatment for hepatitis is lengthy and only effective for approximately half of treatment-naïve patients, and even fewer patients who failed previous treatment," commented Stefan Zeuzem, Professor of Medicine and Chief, department of medicine, J W Goethe University Hospital, Frankfurt. "If approved, telaprevir would help to significantly improve cure rates and shorten treatment duration for many people living with HCV, compared to current standard treatment."
About the Telaprevir Development Program
To date, more than 2,500 people with HCV genotype 1 have received telaprevir-based therapy (telaprevir combined with the current standard of treatment) as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE trials.8,9,10 The telaprevir clinical development program is the largest conducted to date for any investigational direct-acting antiviral hepatitis C therapy.
- ADVANCE evaluated telaprevir-based regimens in approximately 1,088 treatment-naïve patients with chronic HCV infection. Data from the ADVANCE trial were presented at the 2010 American Association for the Study of Liver Diseases (AASLD) annual meeting in November 2010.8
- ILLUMINATE evaluated the benefits of extending telaprevir-based therapy in 540 treatment-naïve patients whose HCV was undetectable at weeks 4 and 12 of treatment. 322 of these patients were randomized to receive 24 or 48 weeks of treatment, and it was found that there was no benefit to extending treatment to 48 weeks. Data from the ILLUMINATE meeting were presented at AASLD in November 2010.9
- REALIZE evaluated telaprevir-based regimens in approximately 650 treatment-failure HCV patients. Data from the REALIZE trial will likely be published in 2011.
Telaprevir is being developed by Tibotec BVBA, an affiliate company of Janssen, in collaboration with Vertex Pharmaceuticals and Mitsubishi Tanabe Pharma for the treatment of genotype 1 HCV in combination with pegylated-interferon and ribavirin in both patients who have failed prior treatment and those who have never been treated. Tibotec BVBA has the commercialisation rights for telaprevir in Europe, Latin America, the Middle East, Africa, India, Australia and New Zealand, pending approval by the respective regulatory authorities. Vertex will commercialise telaprevir in the U.S., Canada and Mexico and Mitsubishi Tanabe Pharma has rights to commercialise telaprevir in Japan and certain Far East countries.
About Tibotec BVBA
Tibotec BVBA is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and HCV drugs, and anti-infectives for diseases of high unmet medical need.
Idera Pharmaceuticals reports positive antiviral results from phase 1 study for Hep C drug
Idera Pharmaceuticals (Nasdaq: IDRA) announced Monday positive preliminary results from a phase 1 study for IMO-2125, the company's investigational drug treatment for chronic hepatitis C infection.
Hep C is an infectious disease affecting the liver. It is often asymptomatic, but once established, chronic infection can progress to scarring of the liver. In some cases, people will go on to develop liver failure or other complications, including liver cancer.
During the 4-week dose-ranging trial, the IMO-2125 drug was tested in combination with ribavirin, in 60 patients with the virus. The results indicated a "substantial decline" in virus levels at two days after the first dose of IMO-2125, and after four weeks of treatment, the company said.
In addition, liver enzymes decreased during the treatment period and were within the normal range by the end of the fourth week in the majority of IMO-2125-treated patients.
"In this study, IMO-2125 plus ribavirin was well tolerated with no treatment-related discontinuations, and demonstrated substantial antiviral activity," said vice president of clinical development, Robert Arbeit.
Idera develops drug candidates that act by modulating immune responses through specific Toll-like Receptors (TLRs).
TLRs, a family of immune system receptors and the immune system's first line of defense, recognize pathogens, or infectious agents, and initiate an immune response.
IMO-2125 is designed to stimulate the immune system, causing the body to generate natural interferons and other antiviral cytokines, or protein regulating molecules.
The company said it is now planning a 12-week phase 2 trial of the drug, which it expects will determine optimal dosing and provide longer term safety and antiviral activity data. Recruitment for the study is anticipated to begin in the first quarter of next year.
Idera was up more than 7% on Monday morning, trading at $2.53 as of 11:30am EST
Hep C is an infectious disease affecting the liver. It is often asymptomatic, but once established, chronic infection can progress to scarring of the liver. In some cases, people will go on to develop liver failure or other complications, including liver cancer.
During the 4-week dose-ranging trial, the IMO-2125 drug was tested in combination with ribavirin, in 60 patients with the virus. The results indicated a "substantial decline" in virus levels at two days after the first dose of IMO-2125, and after four weeks of treatment, the company said.
In addition, liver enzymes decreased during the treatment period and were within the normal range by the end of the fourth week in the majority of IMO-2125-treated patients.
"In this study, IMO-2125 plus ribavirin was well tolerated with no treatment-related discontinuations, and demonstrated substantial antiviral activity," said vice president of clinical development, Robert Arbeit.
Idera develops drug candidates that act by modulating immune responses through specific Toll-like Receptors (TLRs).
TLRs, a family of immune system receptors and the immune system's first line of defense, recognize pathogens, or infectious agents, and initiate an immune response.
IMO-2125 is designed to stimulate the immune system, causing the body to generate natural interferons and other antiviral cytokines, or protein regulating molecules.
The company said it is now planning a 12-week phase 2 trial of the drug, which it expects will determine optimal dosing and provide longer term safety and antiviral activity data. Recruitment for the study is anticipated to begin in the first quarter of next year.
Idera was up more than 7% on Monday morning, trading at $2.53 as of 11:30am EST
Saturday, December 18, 2010
SciClone drops development of SCV-07 for previous HCV therapy relapsers....
"We are probably going to see more companies drop development programs for HCV therapies as the treatment landscape and probabilities of advancement for competitive compounds continues to increase. At some point, the sponsoring company has to make a decision based on simple cost/benefit ratios and potential for a compound to sustain itself in what will become a crowded market. SciClone will continue its development program for SCV-07 for oral mucositis in patients with head and neck cancer - Chris"
FOSTER CITY, CA -- (MARKET WIRE) -- 12/15/10 -- SciClone Pharmaceuticals, Inc. (NASDAQ: SCLN) today announced topline results from the Company's phase 2b clinical trial of SCV-07 for the treatment of hepatitis C (HCV). The study evaluated the safety and immunomodulatory effects of SCV-07 as a monotherapy and in combination with ribavirin in relapsed HCV patients. Study data demonstrated SCV-07 to be safe and well-tolerated at both administered doses. Topline results showed a clear biological signal from SCV-07 but did not meet the study's primary efficacy endpoint of a 2 log reduction in viral load from baseline level. A secondary measure of efficacy, defined as a reduction in viral load of greater than 0.5 log from baseline level, was seen in 38.5% of the low-dose patients (5/13) and in 44.4% of the high-dose patients (8/18). Additionally, while no patients in the low-dose group achieved greater than a 1 log reduction, 3 of the high-dose patients achieved greater than a 1 log reduction in viral load. This proof of concept study was designed to provide an estimate of SCV-07's treatment effect in relapsed HCV patients and guide further studies of SCV-07 in addressing this chronic infection.
"Although the data showed an interesting biological signal, due to the rapidly changing landscape of effective treatments which increase the complexity and risks of developing drugs in chronic HCV, we have decided not to continue development in this indication. On another front, we continue to be excited about the potential for SCV-07 in the prevention of oral mucositis in patients with head and neck cancer and the initiation of our phase 2b study, which should begin by early 2011," stated Friedhelm Blobel, Ph.D., President and Chief Executive Officer of SciClone. "Our primary focus remains on rapidly growing our commercially successful specialty pharmaceutical business in China and other key emerging markets to increase profitability and generate cash for our shareholders."
Study Design
The phase 2b multicenter, multi-dose, open-label study was designed to evaluate the safety and immunomodulatory effects of SCV-07 as a monotherapy or in combination with ribavirin in non-cirrhotic patients with genotype 1 chronic HCV who have relapsed after at least 44 weeks of treatment with pegylated interferon and ribavirin. The study, which also monitored biomarkers of immune activation and HCV viral load dynamics, included two treatment cohorts of 20 patients each who received SCV-07 at a dose of either 0.1 mg/kg or 1.0 mg/kg. The eight week treatment period included four weeks of SCV-07 monotherapy followed by four weeks of SCV-07 in combination with ribavirin. The trial also included three follow-up visits within seven weeks after the completion of treatment.
About SCV-07
SCV-07 (gamma-D-glutamyl-L-tryptophan) is a small molecule which appears to stimulate the immune system through inhibition of STAT3 signaling and the resulting effects on T-helper 1 cells. SCV-07 has been shown to be efficacious in animal models of immune-sensitive diseases, including prevention of oral mucositis, treatment of cancer, viral infections, and enhancement of response to vaccines.
Additionally, SciClone is currently planning to initiate a phase 2b study of SCV-07 for the prevention of oral mucositis by early 2011. As compared to the company's recently completed phase 2a trial, the phase 2b study design is expected to include higher doses of SCV-07 and be adequately powered to demonstrate statistical significance. Additionally, researchers expect to continue to investigate the role of specific genetic profiles on patient response to SCV-07, as well as the potential link between cytokine activity and SCV-07's sub-cellular mechanism of action.
SCV-07 is protected by composition of matter patents as well as multiple method of treatment patents. SciClone has exclusive worldwide rights to SCV-07 outside of Russia, where the molecule has recently been approved for stimulation of depressed immune systems.
About SciClone
SciClone Pharmaceuticals (NASDAQ: SCLN) is a revenue-generating, China-centric, specialty pharmaceutical company with a substantial international business and a product portfolio of novel therapies for cancer and infectious diseases. The Company is focused on continuing sales growth and executing a clinical development strategy with prudently managed costs. ZADAXIN® (thymalfasin) is approved in over 30 countries for the treatment of hepatitis B (HBV) and hepatitis C (HCV), certain cancers, and as a vaccine adjuvant. In addition to further studying thymalfasin's use as a vaccine enhancer, SciClone is planning to evaluate SCV-07 in a phase 2b trial to modify the course of oral mucositis in patients with head and neck cancer; and recently completed a phase 2b trial of SCV-07 for the treatment of HCV. The Company also has exclusive commercialization and distribution rights in China to a novel treatment for advanced liver cancer, DC Bead®, currently under review by regulatory agencies in that country. Additionally, SciClone owns exclusive commercialization and distribution rights to the anti-nausea drug ondansetron RapidFilm® in China, including Hong Kong and Macau, and Vietnam. The Company intends to seek regulatory approval for the product, commonly used to treat and prevent nausea and vomiting caused by chemotherapy, radiotherapy, and surgery, in these markets. For additional information, please visit www.sciclone.com.
Forward-looking statements
The information in this press release contains forward-looking statements, including our expectations and beliefs regarding the timing and results of our clinical trials. You are urged to consider statements that include the words "may," "will," "would," "could," "should," "might," "believes," "estimates," "projects," "potential," "expects," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. These statements are subject to risks and uncertainties that are difficult to predict and actual outcomes may differ materially. These risks and uncertainties include our forward-looking statements regarding our commercial and development objectives because of uncertainties, including future sales, product pricing, the timing of clinical trial events such as patient enrollment, requirements of, and future actions of, the U.S. Food and Drug Administration, the fact that experimental data, and clinical results derived from studies with animals or a limited group of patients, as well as comparisons with other clinical trials, may not be predictive of the results of larger studies and, therefore, such experimental or clinical data are not necessarily predictive indicative of the efficacy or safety or the results of larger studies and clinical trials. Please also refer to the other risks and uncertainties described in SciClone's filings with the Securities and Exchange Commission. All forward-looking statements are based on information currently available to SciClone, and SciClone assumes no obligation to update any such forward-looking statements.
DC Bead is a registered trademark of Biocompatibles UK Limited.
RapidFilm is a registered trademark of Labtec Gesellschaft für technologische Forschung und Entwicklung mbH.
Source: SciClone Pharmaceuticals, Inc.
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FOSTER CITY, CA -- (MARKET WIRE) -- 12/15/10 -- SciClone Pharmaceuticals, Inc. (NASDAQ: SCLN) today announced topline results from the Company's phase 2b clinical trial of SCV-07 for the treatment of hepatitis C (HCV). The study evaluated the safety and immunomodulatory effects of SCV-07 as a monotherapy and in combination with ribavirin in relapsed HCV patients. Study data demonstrated SCV-07 to be safe and well-tolerated at both administered doses. Topline results showed a clear biological signal from SCV-07 but did not meet the study's primary efficacy endpoint of a 2 log reduction in viral load from baseline level. A secondary measure of efficacy, defined as a reduction in viral load of greater than 0.5 log from baseline level, was seen in 38.5% of the low-dose patients (5/13) and in 44.4% of the high-dose patients (8/18). Additionally, while no patients in the low-dose group achieved greater than a 1 log reduction, 3 of the high-dose patients achieved greater than a 1 log reduction in viral load. This proof of concept study was designed to provide an estimate of SCV-07's treatment effect in relapsed HCV patients and guide further studies of SCV-07 in addressing this chronic infection.
"Although the data showed an interesting biological signal, due to the rapidly changing landscape of effective treatments which increase the complexity and risks of developing drugs in chronic HCV, we have decided not to continue development in this indication. On another front, we continue to be excited about the potential for SCV-07 in the prevention of oral mucositis in patients with head and neck cancer and the initiation of our phase 2b study, which should begin by early 2011," stated Friedhelm Blobel, Ph.D., President and Chief Executive Officer of SciClone. "Our primary focus remains on rapidly growing our commercially successful specialty pharmaceutical business in China and other key emerging markets to increase profitability and generate cash for our shareholders."
Study Design
The phase 2b multicenter, multi-dose, open-label study was designed to evaluate the safety and immunomodulatory effects of SCV-07 as a monotherapy or in combination with ribavirin in non-cirrhotic patients with genotype 1 chronic HCV who have relapsed after at least 44 weeks of treatment with pegylated interferon and ribavirin. The study, which also monitored biomarkers of immune activation and HCV viral load dynamics, included two treatment cohorts of 20 patients each who received SCV-07 at a dose of either 0.1 mg/kg or 1.0 mg/kg. The eight week treatment period included four weeks of SCV-07 monotherapy followed by four weeks of SCV-07 in combination with ribavirin. The trial also included three follow-up visits within seven weeks after the completion of treatment.
About SCV-07
SCV-07 (gamma-D-glutamyl-L-tryptophan) is a small molecule which appears to stimulate the immune system through inhibition of STAT3 signaling and the resulting effects on T-helper 1 cells. SCV-07 has been shown to be efficacious in animal models of immune-sensitive diseases, including prevention of oral mucositis, treatment of cancer, viral infections, and enhancement of response to vaccines.
Additionally, SciClone is currently planning to initiate a phase 2b study of SCV-07 for the prevention of oral mucositis by early 2011. As compared to the company's recently completed phase 2a trial, the phase 2b study design is expected to include higher doses of SCV-07 and be adequately powered to demonstrate statistical significance. Additionally, researchers expect to continue to investigate the role of specific genetic profiles on patient response to SCV-07, as well as the potential link between cytokine activity and SCV-07's sub-cellular mechanism of action.
SCV-07 is protected by composition of matter patents as well as multiple method of treatment patents. SciClone has exclusive worldwide rights to SCV-07 outside of Russia, where the molecule has recently been approved for stimulation of depressed immune systems.
About SciClone
SciClone Pharmaceuticals (NASDAQ: SCLN) is a revenue-generating, China-centric, specialty pharmaceutical company with a substantial international business and a product portfolio of novel therapies for cancer and infectious diseases. The Company is focused on continuing sales growth and executing a clinical development strategy with prudently managed costs. ZADAXIN® (thymalfasin) is approved in over 30 countries for the treatment of hepatitis B (HBV) and hepatitis C (HCV), certain cancers, and as a vaccine adjuvant. In addition to further studying thymalfasin's use as a vaccine enhancer, SciClone is planning to evaluate SCV-07 in a phase 2b trial to modify the course of oral mucositis in patients with head and neck cancer; and recently completed a phase 2b trial of SCV-07 for the treatment of HCV. The Company also has exclusive commercialization and distribution rights in China to a novel treatment for advanced liver cancer, DC Bead®, currently under review by regulatory agencies in that country. Additionally, SciClone owns exclusive commercialization and distribution rights to the anti-nausea drug ondansetron RapidFilm® in China, including Hong Kong and Macau, and Vietnam. The Company intends to seek regulatory approval for the product, commonly used to treat and prevent nausea and vomiting caused by chemotherapy, radiotherapy, and surgery, in these markets. For additional information, please visit www.sciclone.com.
Forward-looking statements
The information in this press release contains forward-looking statements, including our expectations and beliefs regarding the timing and results of our clinical trials. You are urged to consider statements that include the words "may," "will," "would," "could," "should," "might," "believes," "estimates," "projects," "potential," "expects," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. These statements are subject to risks and uncertainties that are difficult to predict and actual outcomes may differ materially. These risks and uncertainties include our forward-looking statements regarding our commercial and development objectives because of uncertainties, including future sales, product pricing, the timing of clinical trial events such as patient enrollment, requirements of, and future actions of, the U.S. Food and Drug Administration, the fact that experimental data, and clinical results derived from studies with animals or a limited group of patients, as well as comparisons with other clinical trials, may not be predictive of the results of larger studies and, therefore, such experimental or clinical data are not necessarily predictive indicative of the efficacy or safety or the results of larger studies and clinical trials. Please also refer to the other risks and uncertainties described in SciClone's filings with the Securities and Exchange Commission. All forward-looking statements are based on information currently available to SciClone, and SciClone assumes no obligation to update any such forward-looking statements.
DC Bead is a registered trademark of Biocompatibles UK Limited.
RapidFilm is a registered trademark of Labtec Gesellschaft für technologische Forschung und Entwicklung mbH.
Source: SciClone Pharmaceuticals, Inc.
News Provided by Acquire Media
Tuesday, December 14, 2010
Pharmasset exploring interferon-sparing Phase II trial for it's nucelotide analog PSI-7977 for Genotype 2/3 HCV...
Possible great niche for PSI-7977 in Genotype 2/3 subjects, possibly cutting the duration of therapy in half for these patients and possibly taking the interferon component out of the equation. -Chris
Pharmasset Initiates Exploratory Interferon Sparing Clinical Trial of PSI-7977 for Chronic Hepatitis C
Exploratory phase 2 trial in patients with HCV genotype 2 or 3 to receive PSI-7977 400mg QD and ribavirin, with 0-12 weeks of pegylated interferon
Interim data expected in first half of 2011
PRINCETON, N.J., Dec. 14, 2010 /PRNewswire/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that dosing has begun in an exploratory study of PSI-7977, a nucleotide analog polymerase inhibitor, for the treatment of chronic hepatitis C (HCV). The trial will evaluate PSI-7977 400mg QD in combination with ribavirin (RBV), with 0, 4, 8, or 12 weeks of pegylated interferon alfa 2a (Peg-IFN) in treatment-naive patients infected with HCV genotype 2 or 3.
"Based on the encouraging efficacy, safety and resistance data from the Phase 2a trial with PSI-7977 in combination with pegylated interferon and ribavirin, we initiated a study to explore shorter durations of interferon, including an interferon-free regimen in treatment naïve patients with HCV genotype 2 or 3," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "An important limitation to the current treatment of HCV patients is the use of interferon with its associated side effect profile. We believe that PSI-7977's high barrier to resistance and the lack of a significant effect of IL28B genotype in the Phase 2a trial provide us an opportunity with PSI-7977 to explore shorter durations of interferon, and potentially even removing it from the treatment regimen altogether."
About the Trial
The trial is anticipated to enroll approximately 40 patients infected with HCV genotype 2 or 3 who have not previously been treated. The primary endpoint of the trial will be the assessment of safety and tolerability of PSI-7977 400mg QD and RBV for 12 weeks, administered with or without pegylated interferon (Peg-IFN) in treatment naïve patients with HCV genotypes 2 or 3. The trial will be conducted in New Zealand. Patients will be randomized into one of 4 arms:
-- PSI-7977 400mg QD in combination with RBV for 12 weeks (no interferon);
-- PSI-7977 400mg QD in combination with RBV for 12 weeks, with only 4 weeks of Peg-IFN;
-- PSI-7977 400mg QD in combination with RBV for 12 weeks, with only 8 weeks of Peg-IFN;
-- PSI-7977 400mg QD in combination with Peg-IFN and RBV for 12 weeks.
Patients will be stratified by HCV genotype and IL28B status to ensure balance across cohorts.
Pharmasset anticipates reporting interim data from this trial in the first half of 2011.
About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog that has recently initiated dosing in a Phase 2b study in patients with HCV genotypes 1, 2, or 3, and PSI-938, an unpartnered guanosine nucleotide analog which recently completed a 7-day monotherapy study. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development.
Pharmasset Initiates Exploratory Interferon Sparing Clinical Trial of PSI-7977 for Chronic Hepatitis C
Exploratory phase 2 trial in patients with HCV genotype 2 or 3 to receive PSI-7977 400mg QD and ribavirin, with 0-12 weeks of pegylated interferon
Interim data expected in first half of 2011
PRINCETON, N.J., Dec. 14, 2010 /PRNewswire/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that dosing has begun in an exploratory study of PSI-7977, a nucleotide analog polymerase inhibitor, for the treatment of chronic hepatitis C (HCV). The trial will evaluate PSI-7977 400mg QD in combination with ribavirin (RBV), with 0, 4, 8, or 12 weeks of pegylated interferon alfa 2a (Peg-IFN) in treatment-naive patients infected with HCV genotype 2 or 3.
"Based on the encouraging efficacy, safety and resistance data from the Phase 2a trial with PSI-7977 in combination with pegylated interferon and ribavirin, we initiated a study to explore shorter durations of interferon, including an interferon-free regimen in treatment naïve patients with HCV genotype 2 or 3," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "An important limitation to the current treatment of HCV patients is the use of interferon with its associated side effect profile. We believe that PSI-7977's high barrier to resistance and the lack of a significant effect of IL28B genotype in the Phase 2a trial provide us an opportunity with PSI-7977 to explore shorter durations of interferon, and potentially even removing it from the treatment regimen altogether."
About the Trial
The trial is anticipated to enroll approximately 40 patients infected with HCV genotype 2 or 3 who have not previously been treated. The primary endpoint of the trial will be the assessment of safety and tolerability of PSI-7977 400mg QD and RBV for 12 weeks, administered with or without pegylated interferon (Peg-IFN) in treatment naïve patients with HCV genotypes 2 or 3. The trial will be conducted in New Zealand. Patients will be randomized into one of 4 arms:
-- PSI-7977 400mg QD in combination with RBV for 12 weeks (no interferon);
-- PSI-7977 400mg QD in combination with RBV for 12 weeks, with only 4 weeks of Peg-IFN;
-- PSI-7977 400mg QD in combination with RBV for 12 weeks, with only 8 weeks of Peg-IFN;
-- PSI-7977 400mg QD in combination with Peg-IFN and RBV for 12 weeks.
Patients will be stratified by HCV genotype and IL28B status to ensure balance across cohorts.
Pharmasset anticipates reporting interim data from this trial in the first half of 2011.
About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog that has recently initiated dosing in a Phase 2b study in patients with HCV genotypes 1, 2, or 3, and PSI-938, an unpartnered guanosine nucleotide analog which recently completed a 7-day monotherapy study. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development.
Monday, December 13, 2010
"Concord Monitor" article assess the US Government's response to Hepatitis C.
SPOILER ALERT!! No, the Gov't hasn't responded all that well, but some important progress is being made. Read about it here.
Thursday, December 9, 2010
Lab21 secures new patents in Hepatitis C drug resistance and fluorescent carbon-based nanoparticle technology
Diagnostics for HCV resistance seems to me to be a lucrative niche to fill with the up coming small molecules for HCV. Lab21 looks fully poised for growth with both this and other diagnostics related to personal medicine - Chris
Cambridge, UK, December 8th - Lab21 Limited, the Cambridge, UK-based specialist in personalised medicine has secured new patents in Europe and the USA relating to Hepatitis C and its SelahDOTS™ fluorescent nanoparticles, as it continues to expand its intellectual property portfolio.
The hepatitis C patent extends an existing patent, and refers to technology allowing the genotypic identification of drug resistant mutations in the 4 major global genotypes of HCV. With the imminent launch of a series of new small molecule therapies in HCV, this technology will allow accurate monitoring of when drug resistance appears in individual patients, improving patient care.
The SelahDOTS™ nanoparticles technology covers a generic approach to the development of new diagnostic and imaging reagents using carbon-based non-toxic nanoparticles. This platform technology has multiple applications in clinical diagnostics and was originally developed through a licence from Clemson University. The grant of the patent now allows Lab21 to develop a series of new product and service applications in areas such as in vivo imaging, immunodiagnostics and point-of-care biomarker analysis,
The securing of these patents builds on Lab21’s growing intellectual property portfolio as it expands its competitive proprietary position in pharmacogenetic markers, disease markers and its assay technology.
Dr Berwyn Clarke, CSO at Lab21 commented: ‘The HCV patent further strengthens our portfolio in the important HCV diagnostic area while the nanoparticle platform technology has potential to transform the ways in which particulate diagnostics are used, particularly in vivo, where particle-related toxicity has been a significant problem. Additionally we are seeing early development progress in incorporating the SelahDOTS™ technology in our own new molecular and protein based assays’
Graham Mullis, Lab21 CEO added: ‘The development of an extensive intellectual property portfolio will be an important part of Lab21’s strategy as we continue to grow. Patents such as these will ensure we are able to remain uniquely competitive and ensure we are able to provide our customers with the most advanced products and services in the markets we choose to serve.’
Cambridge, UK, December 8th - Lab21 Limited, the Cambridge, UK-based specialist in personalised medicine has secured new patents in Europe and the USA relating to Hepatitis C and its SelahDOTS™ fluorescent nanoparticles, as it continues to expand its intellectual property portfolio.
The hepatitis C patent extends an existing patent, and refers to technology allowing the genotypic identification of drug resistant mutations in the 4 major global genotypes of HCV. With the imminent launch of a series of new small molecule therapies in HCV, this technology will allow accurate monitoring of when drug resistance appears in individual patients, improving patient care.
The SelahDOTS™ nanoparticles technology covers a generic approach to the development of new diagnostic and imaging reagents using carbon-based non-toxic nanoparticles. This platform technology has multiple applications in clinical diagnostics and was originally developed through a licence from Clemson University. The grant of the patent now allows Lab21 to develop a series of new product and service applications in areas such as in vivo imaging, immunodiagnostics and point-of-care biomarker analysis,
The securing of these patents builds on Lab21’s growing intellectual property portfolio as it expands its competitive proprietary position in pharmacogenetic markers, disease markers and its assay technology.
Dr Berwyn Clarke, CSO at Lab21 commented: ‘The HCV patent further strengthens our portfolio in the important HCV diagnostic area while the nanoparticle platform technology has potential to transform the ways in which particulate diagnostics are used, particularly in vivo, where particle-related toxicity has been a significant problem. Additionally we are seeing early development progress in incorporating the SelahDOTS™ technology in our own new molecular and protein based assays’
Graham Mullis, Lab21 CEO added: ‘The development of an extensive intellectual property portfolio will be an important part of Lab21’s strategy as we continue to grow. Patents such as these will ensure we are able to remain uniquely competitive and ensure we are able to provide our customers with the most advanced products and services in the markets we choose to serve.’
Tuesday, December 7, 2010
Medivir raises $41 million from institutional investors for TMC435 and beyond....
Medivir Creates Runway for TMC435 with $41M Placement
By Nuala Moran
BioWorld International Correspondent
LONDON – Medivir AB raised €30.8 million (US$41 million) in a private placement that brings in international institutional investors in the lead up to the start of Phase III trials of the lead product, TMC435, a protease inhibitor for treating hepatitis C (HCV) infections.
"The strategy is to broaden the shareholder base outside Scandinavia," said Rein Piir, CFO. All the new shareholders are, "high-quality, top-rank, U.S., Swiss, Dutch and UK investors," he told a teleconference held to discuss the placement.
In total, Huddinge, Denmark-based Medivir issued 2.25 million new shares at SEK125 ($18.23) each to 30 international institutional investors, plus some institutions in Sweden that were not already shareholders.
That represented a 7.9 percent dilution for existing investors. More than two-thirds of the new shares were taken up by international investors. Medivir is quoted on the Nasdaq OMX Exchange in Stockholm.
"This will enable Medivir to strengthen its R&D and take a higher amount of value going forward, by doing joint ventures rather than licensing, and [allowing us to] take products further," Piir said.
Medivir announced its intention of doing the placing in March when it sought approval from shareholders, but its ability to do so rests on positive Phase IIb data for TMC 435. The product is partnered by Johnson & Johnson subsidiary Tibotec Pharmaceuticals Ltd., with Medivir retaining rights in Nordic markets.
Last month, Medivir announced positive interim data from Aspire, a Phase IIb study of TMC 435 as a once-daily therapy in 462 HCV patients who had been treated previously with pegylated interferon (peg-INF).
TMC 435, added to standard of care, increased the number of patients whose HCV levels were undetectable at 24 weeks.
Across four treatment groups, between 79 percent and 86 percent of patients were able to stop taking any therapy at 24 weeks. Patients in the study were infected with genotype 1 HCV, which is hard to treat.
The product also had positive results in a 386-subject Phase IIb study in treatment-naïve patients, which reported in July. Here, 83 percent of those treated with TMC 435 were able to stop all therapy at 24 weeks.
Those results were presented by Tibotec at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, in October.
"We witnessed enthusiasm for TMC435 at the AASLD clinical meeting, which together with positive Phase IIb Aspire results, boosts our confidence and price target, by 6 percent," noted Peter Welford, equity analyst at Jeffries in London
The shares closed at SEK120 on Dec. 3, the day the completion of the placing was announced. Welford added that Medivir is, "The European biotech best placed to benefit from broad enthusiasm for the wave of new blockbuster hepatitis C therapies reaching the market."
Building on the success of TMC 435, the company has other HCV products coming through its pipeline. "Investors are supporting Medivir in efforts to become a leading player in HCV," Piir said.
The company also intends to apply its technology to new therapeutic areas. "We are in discussion on [doing] this in a joint venture structure," Piir added.
By Nuala Moran
BioWorld International Correspondent
LONDON – Medivir AB raised €30.8 million (US$41 million) in a private placement that brings in international institutional investors in the lead up to the start of Phase III trials of the lead product, TMC435, a protease inhibitor for treating hepatitis C (HCV) infections.
"The strategy is to broaden the shareholder base outside Scandinavia," said Rein Piir, CFO. All the new shareholders are, "high-quality, top-rank, U.S., Swiss, Dutch and UK investors," he told a teleconference held to discuss the placement.
In total, Huddinge, Denmark-based Medivir issued 2.25 million new shares at SEK125 ($18.23) each to 30 international institutional investors, plus some institutions in Sweden that were not already shareholders.
That represented a 7.9 percent dilution for existing investors. More than two-thirds of the new shares were taken up by international investors. Medivir is quoted on the Nasdaq OMX Exchange in Stockholm.
"This will enable Medivir to strengthen its R&D and take a higher amount of value going forward, by doing joint ventures rather than licensing, and [allowing us to] take products further," Piir said.
Medivir announced its intention of doing the placing in March when it sought approval from shareholders, but its ability to do so rests on positive Phase IIb data for TMC 435. The product is partnered by Johnson & Johnson subsidiary Tibotec Pharmaceuticals Ltd., with Medivir retaining rights in Nordic markets.
Last month, Medivir announced positive interim data from Aspire, a Phase IIb study of TMC 435 as a once-daily therapy in 462 HCV patients who had been treated previously with pegylated interferon (peg-INF).
TMC 435, added to standard of care, increased the number of patients whose HCV levels were undetectable at 24 weeks.
Across four treatment groups, between 79 percent and 86 percent of patients were able to stop taking any therapy at 24 weeks. Patients in the study were infected with genotype 1 HCV, which is hard to treat.
The product also had positive results in a 386-subject Phase IIb study in treatment-naïve patients, which reported in July. Here, 83 percent of those treated with TMC 435 were able to stop all therapy at 24 weeks.
Those results were presented by Tibotec at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, in October.
"We witnessed enthusiasm for TMC435 at the AASLD clinical meeting, which together with positive Phase IIb Aspire results, boosts our confidence and price target, by 6 percent," noted Peter Welford, equity analyst at Jeffries in London
The shares closed at SEK120 on Dec. 3, the day the completion of the placing was announced. Welford added that Medivir is, "The European biotech best placed to benefit from broad enthusiasm for the wave of new blockbuster hepatitis C therapies reaching the market."
Building on the success of TMC 435, the company has other HCV products coming through its pipeline. "Investors are supporting Medivir in efforts to become a leading player in HCV," Piir said.
The company also intends to apply its technology to new therapeutic areas. "We are in discussion on [doing] this in a joint venture structure," Piir added.
Monday, December 6, 2010
Bruce Bacon, MD on Boceprevir RESPOND-2 study....
Research Fuels Hope for Hard-To-Treat Hepatitis C Patients
Released: 12/6/2010 12:00 PM EST
Source: Saint Louis University Medical Center
Newswise — The outlook for patients with hepatitis C continues to improve as results from a clinical trial led by a Saint Louis University researcher found that the drug boceprevir helped cure hard-to-treat patients. The findings were reported at the 61st annual meeting of the American Association for the Study of Liver Disease’s earlier in November.
Bruce R. Bacon, M.D., professor of internal medicine at Saint Louis University School of Medicine and co-principal investigator of the HCV RESPOND-2 study, studied the protease inhibitor, boceprevir, and found that it significantly increased the number of patients whose blood had undetectable levels of the virus.
“These findings are especially significant for patients who don’t respond to initial treatment,” said Bacon. “When the hepatitis C virus is not eliminated, debilitating fatigue and more serious problems can follow.”
Hepatitis C is caused by a virus that is transmitted by contact with blood. The infection may initially be asymptomatic, but for patients who develop chronic hepatitis C infection, inflammation of the liver may develop, leading to fibrosis and cirrhosis (scarring of the liver), as well as other complications including liver cancer and death.
The prognosis varies for patients with chronic hepatitis C. With the current standard therapy, about half fully recover after an initial course of peginterferon and ribavirin anti-viral therapy that may last from six months to a year.
The remaining patients, known as non-responders, may improve with initial treatment but the virus is not eliminated, or may not respond to treatment at all.
For this group, the only current option is to retreat patients with the same or similar drugs, which increases the likelihood of severe treatment side-effects. In addition, researchers have found that the success of treatment depends on the major strain, or genotype, of hepatitis C that a patient has.
The HCV RESPOND-2 study looked at 403 patients with chronic hepatitis C infections with genotype one, the most difficult strain of the virus to treat, who still had significant levels of the virus after being treated with peginterferon and ribavirin, the standard hepatitis C treatment.
"These results are very exciting," Bacon said. “In this study, boceprevir helped cure significantly more patients in 24 weeks of therapy than did treatment with peginterferon and ribavirin alone."
A second study, HCV SPRINT-2, examined patients with hepatitis C with genotype one who had not yet been treated with the standard treatment. They, too, responded well to the drug.
Bacon calls the progress made in treating hepatitis C remarkable.
“We’ve gone from the discovery of the virus in 1989 to where we are now, 22 years later, when we have the ability to cure a large majority of those with hepatitis C,” Bacon said. “It’s a true success story.”
“Drugs like boceprevir are going to revolutionize care of those with hepatitis C.”
The clinical trial was funded by Merck, which expects to begin seeking FDA approval this year.
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious disease.
Released: 12/6/2010 12:00 PM EST
Source: Saint Louis University Medical Center
Newswise — The outlook for patients with hepatitis C continues to improve as results from a clinical trial led by a Saint Louis University researcher found that the drug boceprevir helped cure hard-to-treat patients. The findings were reported at the 61st annual meeting of the American Association for the Study of Liver Disease’s earlier in November.
Bruce R. Bacon, M.D., professor of internal medicine at Saint Louis University School of Medicine and co-principal investigator of the HCV RESPOND-2 study, studied the protease inhibitor, boceprevir, and found that it significantly increased the number of patients whose blood had undetectable levels of the virus.
“These findings are especially significant for patients who don’t respond to initial treatment,” said Bacon. “When the hepatitis C virus is not eliminated, debilitating fatigue and more serious problems can follow.”
Hepatitis C is caused by a virus that is transmitted by contact with blood. The infection may initially be asymptomatic, but for patients who develop chronic hepatitis C infection, inflammation of the liver may develop, leading to fibrosis and cirrhosis (scarring of the liver), as well as other complications including liver cancer and death.
The prognosis varies for patients with chronic hepatitis C. With the current standard therapy, about half fully recover after an initial course of peginterferon and ribavirin anti-viral therapy that may last from six months to a year.
The remaining patients, known as non-responders, may improve with initial treatment but the virus is not eliminated, or may not respond to treatment at all.
For this group, the only current option is to retreat patients with the same or similar drugs, which increases the likelihood of severe treatment side-effects. In addition, researchers have found that the success of treatment depends on the major strain, or genotype, of hepatitis C that a patient has.
The HCV RESPOND-2 study looked at 403 patients with chronic hepatitis C infections with genotype one, the most difficult strain of the virus to treat, who still had significant levels of the virus after being treated with peginterferon and ribavirin, the standard hepatitis C treatment.
"These results are very exciting," Bacon said. “In this study, boceprevir helped cure significantly more patients in 24 weeks of therapy than did treatment with peginterferon and ribavirin alone."
A second study, HCV SPRINT-2, examined patients with hepatitis C with genotype one who had not yet been treated with the standard treatment. They, too, responded well to the drug.
Bacon calls the progress made in treating hepatitis C remarkable.
“We’ve gone from the discovery of the virus in 1989 to where we are now, 22 years later, when we have the ability to cure a large majority of those with hepatitis C,” Bacon said. “It’s a true success story.”
“Drugs like boceprevir are going to revolutionize care of those with hepatitis C.”
The clinical trial was funded by Merck, which expects to begin seeking FDA approval this year.
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious disease.
Achillion To Present Data From Studies Of ACH-1625 In Hepatitis C At Asian Pacific Liver Conference
Achillion To Present Data From Studies Of ACH-1625 In Hepatitis C At Asian Pacific Liver Conference
GlobeNewswire
12/06/10 - 07:00 AM EST
NEW HAVEN, Conn., Dec. 6, 2010 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced that data from the Company's ongoing clinical studies of ACH-1625 has been accepted for presentation at the 21st Annual Conference of the Asian Pacific Association for the Study of the Liver (APASL 2011) to be held February 17-21, 2011 in Bangkok, Thailand.
ACH-1625 is an inhibitor of HCV NS3 protease that was discovered and is being developed by Achillion.
The presentation, entitled "Viral Kinetics Modeling of Short-term Monotherapy Data of ACH-1625, an HCV Protease Inhibitor," will be presented by Dr. Atul Agarwal, Senior Director of Computational Chemistry of Achillion. (Abstract A-315-0024-00792.) The presentation describes a mathematical analysis of HCV RNA data collected after oral administration of ACH-1625 in HCV genotype 1 infected subjects. This analysis shows rapid and near complete hepatitis C virus clearance following ACH-1625 administration at all dose levels tested. In addition, mathematical modeling of HCV viral kinetics provided information that allowed for subsequent dose selection for Phase II clinical development of ACH-1625.
"These data support and further demonstrate ACH-1625's robust antiviral activity," said Dr. Agarwal. "With clinical data that demonstrated reductions in viral RNA between 3-4.25 log10, these mathematical data quantitatively show the percentage of total virus cleared after five days of ACH-1625 monotherapy. This data also identifies specific patient population characteristics."
"We are pleased to continue to put forward a large body of scientific and clinical data on ACH-1625," commented Michael D. Kishbauch, Chief Executive Officer of Achillion. "We look forward to completing the current Phase II clinical trial of ACH-1625 to further support its profile as a potential best-in-class protease inhibitor for the treatment of HCV."
About ACH-1625
ACH-1625 is an HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-1625 is an open chain, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-1625 demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures. With its rapid and extensive partitioning to the liver, as well as high liver/plasma ratios demonstrated in preclinical studies, Achillion believes that ACH-1625 has the potential for once daily dosing. ACH-1625 has shown low single-digit nanomolar potency that is specific to HCV. It is equipotent against HCV genotypes 1a and 1b at IC50~1nM.
In clinical studies, HCV-infected patients receiving doses ranging from 200 to 600 mg twice daily, and 400 to 600 mg once daily, showed mean maximal reductions in viral load ranging from of 3.07 log10 to 4.25 log10. Furthermore, all patients had viral loads that remained suppressed for at least 7 days after dosing was completed, maintaining a mean reduction of more than 1log10 from baseline through day 12, the last day of viral load measurement in the study.
GlobeNewswire
12/06/10 - 07:00 AM EST
NEW HAVEN, Conn., Dec. 6, 2010 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced that data from the Company's ongoing clinical studies of ACH-1625 has been accepted for presentation at the 21st Annual Conference of the Asian Pacific Association for the Study of the Liver (APASL 2011) to be held February 17-21, 2011 in Bangkok, Thailand.
ACH-1625 is an inhibitor of HCV NS3 protease that was discovered and is being developed by Achillion.
The presentation, entitled "Viral Kinetics Modeling of Short-term Monotherapy Data of ACH-1625, an HCV Protease Inhibitor," will be presented by Dr. Atul Agarwal, Senior Director of Computational Chemistry of Achillion. (Abstract A-315-0024-00792.) The presentation describes a mathematical analysis of HCV RNA data collected after oral administration of ACH-1625 in HCV genotype 1 infected subjects. This analysis shows rapid and near complete hepatitis C virus clearance following ACH-1625 administration at all dose levels tested. In addition, mathematical modeling of HCV viral kinetics provided information that allowed for subsequent dose selection for Phase II clinical development of ACH-1625.
"These data support and further demonstrate ACH-1625's robust antiviral activity," said Dr. Agarwal. "With clinical data that demonstrated reductions in viral RNA between 3-4.25 log10, these mathematical data quantitatively show the percentage of total virus cleared after five days of ACH-1625 monotherapy. This data also identifies specific patient population characteristics."
"We are pleased to continue to put forward a large body of scientific and clinical data on ACH-1625," commented Michael D. Kishbauch, Chief Executive Officer of Achillion. "We look forward to completing the current Phase II clinical trial of ACH-1625 to further support its profile as a potential best-in-class protease inhibitor for the treatment of HCV."
About ACH-1625
ACH-1625 is an HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-1625 is an open chain, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-1625 demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures. With its rapid and extensive partitioning to the liver, as well as high liver/plasma ratios demonstrated in preclinical studies, Achillion believes that ACH-1625 has the potential for once daily dosing. ACH-1625 has shown low single-digit nanomolar potency that is specific to HCV. It is equipotent against HCV genotypes 1a and 1b at IC50~1nM.
In clinical studies, HCV-infected patients receiving doses ranging from 200 to 600 mg twice daily, and 400 to 600 mg once daily, showed mean maximal reductions in viral load ranging from of 3.07 log10 to 4.25 log10. Furthermore, all patients had viral loads that remained suppressed for at least 7 days after dosing was completed, maintaining a mean reduction of more than 1log10 from baseline through day 12, the last day of viral load measurement in the study.
Wednesday, December 1, 2010
"Sticking Fast To Foil Hepatitis C" article from Chemistry & Engineering News...
A deeper look on Avila Therapeutics development of new protease blockers that irreversibly inhibit the HCV protease enzyme - Chris
Biochemistry: Aiming beyond the active site of a virus's key protease yields selective blockers
Carmen Drahl
By targeting a noncatalytic cysteine, researchers have designed selective irreversible blockers of a protease enzyme essential for hepatitis C virus replication (Nat. Chem. Biol., DOI: 10.1038/nchembio.492).
The work is the first demonstration that steering clear of the active site is a viable design strategy for drugs that react to form a covalent bond to proteases, a broad class of proteins that includes many drug targets. This strategy has already proven useful for blocking other proteins such as kinases.
A team from the biotechnology company Avila Therapeutics developed the new protease blockers, which covalently bind to a cysteine in hepatitis C protease's substrate-binding site. In contrast, most other hepatitis C protease inhibitors in development reversibly bind to a catalytic amino acid common to proteases in human hosts as well as in viruses. Avila's published inhibitor structures are prototypes, but the company hopes to begin human clinical trials with optimized compounds in 2011. The team says its comprehensive structural analysis of hundreds of proteases suggests this strategy can be applied broadly.
However, it's not clear how applicable the team's strategy will be to all proteases, says Matthew S. Bogyo of Stanford University, who develops chemical tools to study the roles of proteases in disease. Nevertheless, "covalent inhibitors benefit from a long duration of action, and when used for clearing pathogens such as hepatitis C virus, they may make more sense than classical reversible inhibitors," Bogyo says. Covalent inhibitors can also make several aspects of drug development more straightforward because it's easier to monitor their target selectivity and distribution throughout the body compared with reversible inhibitors, he adds.
Biochemistry: Aiming beyond the active site of a virus's key protease yields selective blockers
Carmen Drahl
By targeting a noncatalytic cysteine, researchers have designed selective irreversible blockers of a protease enzyme essential for hepatitis C virus replication (Nat. Chem. Biol., DOI: 10.1038/nchembio.492).
The work is the first demonstration that steering clear of the active site is a viable design strategy for drugs that react to form a covalent bond to proteases, a broad class of proteins that includes many drug targets. This strategy has already proven useful for blocking other proteins such as kinases.
A team from the biotechnology company Avila Therapeutics developed the new protease blockers, which covalently bind to a cysteine in hepatitis C protease's substrate-binding site. In contrast, most other hepatitis C protease inhibitors in development reversibly bind to a catalytic amino acid common to proteases in human hosts as well as in viruses. Avila's published inhibitor structures are prototypes, but the company hopes to begin human clinical trials with optimized compounds in 2011. The team says its comprehensive structural analysis of hundreds of proteases suggests this strategy can be applied broadly.
However, it's not clear how applicable the team's strategy will be to all proteases, says Matthew S. Bogyo of Stanford University, who develops chemical tools to study the roles of proteases in disease. Nevertheless, "covalent inhibitors benefit from a long duration of action, and when used for clearing pathogens such as hepatitis C virus, they may make more sense than classical reversible inhibitors," Bogyo says. Covalent inhibitors can also make several aspects of drug development more straightforward because it's easier to monitor their target selectivity and distribution throughout the body compared with reversible inhibitors, he adds.
Further info on the GI-5005 HCV vaccine study presented at AASLD... hope for those with the IL28 T/T allele?
Synopsis of the GI-5005 study presented at AASLD 2010. Overall, the numbers for GI-5005 aren't extraordinary, but certainly worth further studies. The true benefit for this vaccine may be how it appears to illicit a T-cell response in patients carrying the T allele of the IL28 gene, which didn't occur when the same patients were given standard of care
By: DIANA MAHONEY, Internal Medicine News Digital Network
12/01/10
BOSTON – A therapeutic vaccine against the hepatitis C virus was associated with a significantly higher sustained virologic response rate when added to standard-of-care treatment, and the findings justify further development of the vaccine, Dr. Paul Pockros reported at the annual meeting of the American Association for the Study of Liver Diseases.
In the proof-of-concept trial, 133 patients infected with hepatitis C virus (HCV) genotype 1 were randomized to either triple therapy comprising the experimental GI-5005 vaccine, which is designed to elicit a T-cell response specific to HCV, along with pegylated interferon alfa-2b plus ribavirin (P/R), or the standard P/R therapy alone.
The primary outcome measure was sustained virologic response (SVR), defined as undetectable HCV RNA at 6 months after treatment, said Dr. Pockros of the Scripps Clinic in La Jolla, Calif.
The 68 patients in the experimental group initially received monotherapy with the vaccine, consisting of five weekly injections followed by two monthly injections for a 12-week lead-in period, before progressing to the standard-of-care P/R treatment and once-monthly injections. The 65 patients in the control group received standard-of-care P/R treatment alone.
In both groups, the treatment duration was 48 weeks for treatment-naive patients and 72 weeks for those who had a poor or partial response to prior P/R treatment, said Dr. Pockros. Patients in whom prior P/R therapy induced no notable decrease in HCV viral load, as well as those in whom prior treatment initially resulted in undetectable HCV RNA followed by a viral rebound, were excluded from the analysis.
Among the study’s treatment-naive patients, 58% of those who received the vaccine achieved SVR, compared with 48% of those who received P/R alone. Among the prior poor and partial responders, the respective SVR rates in the vaccine and control groups were 17% and 5%, Dr. Pockros reported.
"There was a slight benefit in the treatment-naive and nonresponders, [but] this was numerical only and was not statistically significant," he said. However, the overall benefit in the vaccine vs. control groups was statistically significant, with respective SVR rates of 47% and 35%, he noted.
The vaccine strategy appears to be safe. "The most common associated adverse events were mild, transient injection-site reactions," said Dr. Pockros. Additionally, he stated, "the discontinuation rates due to adverse events were comparable [13%] in both the triple-therapy and standard-of-care arms."
Of particular interest, Dr. Pockros noted, was the T-cell response in a subgroup of difficult-to-treat patients receiving the vaccine. Previous studies have suggested that patients carrying the T allele of the IL28 gene are at high risk of treatment failure with the standard interferon-based therapy. The T-cell response in vaccine-treated patients, as measured by interferon-gamma enzyme-linked ImmunoSpot assay, "mimicked what we saw with a virologic response," he said.
"Four of five T/T allele patients had a T-cell response – one did not actually get treated – but none of the patients who received standard of care had a T-cell response."
This finding is consistent with the hypothesis that the GI-5005 vaccine corrects a fundamental deficit in cellular immunity in IL28B T/T genotype patients, he said. Although the findings need to be confirmed in additional studies with larger patient populations, the vaccine will likely be genotype specific, he noted.
Because the immune response is similar to that observed in HCV-infected patients who are able to clear the virus without treatment, future studies will evaluate the efficacy of monotherapy with the vaccine in genotype-specific patients, Dr. Pockros said.
The proof-of-concept study was funded by GlobeImmune, manufacturer of the vaccine. Dr. Pockros disclosed financial relationships with GlobeImmune, Genentech, Vertex, Merck, Gilead, Abbott, Pfizer, Phenomix, Tibotec, Pharmasset, 3RT, Novartis, Johnson & Johnson, Achillon, Regulus, Debio, Zymogenetics, and Human Genome Sciences.
By: DIANA MAHONEY, Internal Medicine News Digital Network
12/01/10
BOSTON – A therapeutic vaccine against the hepatitis C virus was associated with a significantly higher sustained virologic response rate when added to standard-of-care treatment, and the findings justify further development of the vaccine, Dr. Paul Pockros reported at the annual meeting of the American Association for the Study of Liver Diseases.
In the proof-of-concept trial, 133 patients infected with hepatitis C virus (HCV) genotype 1 were randomized to either triple therapy comprising the experimental GI-5005 vaccine, which is designed to elicit a T-cell response specific to HCV, along with pegylated interferon alfa-2b plus ribavirin (P/R), or the standard P/R therapy alone.
The primary outcome measure was sustained virologic response (SVR), defined as undetectable HCV RNA at 6 months after treatment, said Dr. Pockros of the Scripps Clinic in La Jolla, Calif.
The 68 patients in the experimental group initially received monotherapy with the vaccine, consisting of five weekly injections followed by two monthly injections for a 12-week lead-in period, before progressing to the standard-of-care P/R treatment and once-monthly injections. The 65 patients in the control group received standard-of-care P/R treatment alone.
In both groups, the treatment duration was 48 weeks for treatment-naive patients and 72 weeks for those who had a poor or partial response to prior P/R treatment, said Dr. Pockros. Patients in whom prior P/R therapy induced no notable decrease in HCV viral load, as well as those in whom prior treatment initially resulted in undetectable HCV RNA followed by a viral rebound, were excluded from the analysis.
Among the study’s treatment-naive patients, 58% of those who received the vaccine achieved SVR, compared with 48% of those who received P/R alone. Among the prior poor and partial responders, the respective SVR rates in the vaccine and control groups were 17% and 5%, Dr. Pockros reported.
"There was a slight benefit in the treatment-naive and nonresponders, [but] this was numerical only and was not statistically significant," he said. However, the overall benefit in the vaccine vs. control groups was statistically significant, with respective SVR rates of 47% and 35%, he noted.
The vaccine strategy appears to be safe. "The most common associated adverse events were mild, transient injection-site reactions," said Dr. Pockros. Additionally, he stated, "the discontinuation rates due to adverse events were comparable [13%] in both the triple-therapy and standard-of-care arms."
Of particular interest, Dr. Pockros noted, was the T-cell response in a subgroup of difficult-to-treat patients receiving the vaccine. Previous studies have suggested that patients carrying the T allele of the IL28 gene are at high risk of treatment failure with the standard interferon-based therapy. The T-cell response in vaccine-treated patients, as measured by interferon-gamma enzyme-linked ImmunoSpot assay, "mimicked what we saw with a virologic response," he said.
"Four of five T/T allele patients had a T-cell response – one did not actually get treated – but none of the patients who received standard of care had a T-cell response."
This finding is consistent with the hypothesis that the GI-5005 vaccine corrects a fundamental deficit in cellular immunity in IL28B T/T genotype patients, he said. Although the findings need to be confirmed in additional studies with larger patient populations, the vaccine will likely be genotype specific, he noted.
Because the immune response is similar to that observed in HCV-infected patients who are able to clear the virus without treatment, future studies will evaluate the efficacy of monotherapy with the vaccine in genotype-specific patients, Dr. Pockros said.
The proof-of-concept study was funded by GlobeImmune, manufacturer of the vaccine. Dr. Pockros disclosed financial relationships with GlobeImmune, Genentech, Vertex, Merck, Gilead, Abbott, Pfizer, Phenomix, Tibotec, Pharmasset, 3RT, Novartis, Johnson & Johnson, Achillon, Regulus, Debio, Zymogenetics, and Human Genome Sciences.
Tuesday, November 30, 2010
Caleco Pharma Corp amends IP patents for compounds to treat HCV...
LONG VALLEY, NEW JERSEY--(Marketwire - 11/30/10) - Caleco Pharma Corp. (www.calecopharmacorp.com), a diversified healthcare company with biopharmaceutical and consumer health product development programs that develop products derived from natural sources such as plant extracts, today reports that it has amended its intellectual property (IP) filing with the European Patent Office in The Hague to further secure and strengthen Caleco's anti-viral pipeline.
In response to the EU Patent Office's Examination Report, Caleco reports that the company's European Patent Application number 08725530.3 is amended with regard to compositions comprising derivatives and derivative combinations of Lamiridosin and Iridoid for treatment of Hepatitis C. The molecular specifications required in these amendments resulted in the exclusion of certain derivative claims. However, these claims will not be abandoned, but instead, these claims will be pursued through one or more divisional applications.
John Boschert, Caleco's CEO, said, "By amending our filing we are seeking to solidify our intellectual property position in the billion dollar Hepatitis C and anti-viral marketplace. We plan to continue to pursue a broader pipeline of semi-synthetic derivatives that will be prepared for further testing in 2011. The Hepatitis C patient population remains greatly underserved by existing treatment options and we are eager to move these compounds into the next stage of development."
About Caleco Pharma Corp.
Caleco is focused on the ongoing research and development of its pipeline of over-the-counter and prescription medications including its proprietary antiviral and "Liver Health" OTC formulations. In addition Caleco is developing Dermatological Products based on the active ingredients found in its proprietary formulation. Caleco's intellectual property covering the Liver Health formulations and derivatives consists of patent applications in the United States, Europe and Canada and four European Drug Master File applications.
Caleco's shares are traded in the United States on the OTC Bulletin Board (OTC.BB:CAEH - News) and in Germany on the Frankfurt Stock Exchange (Frankfurt:T3R - News)(WKN: A0N9Y0).
In response to the EU Patent Office's Examination Report, Caleco reports that the company's European Patent Application number 08725530.3 is amended with regard to compositions comprising derivatives and derivative combinations of Lamiridosin and Iridoid for treatment of Hepatitis C. The molecular specifications required in these amendments resulted in the exclusion of certain derivative claims. However, these claims will not be abandoned, but instead, these claims will be pursued through one or more divisional applications.
John Boschert, Caleco's CEO, said, "By amending our filing we are seeking to solidify our intellectual property position in the billion dollar Hepatitis C and anti-viral marketplace. We plan to continue to pursue a broader pipeline of semi-synthetic derivatives that will be prepared for further testing in 2011. The Hepatitis C patient population remains greatly underserved by existing treatment options and we are eager to move these compounds into the next stage of development."
About Caleco Pharma Corp.
Caleco is focused on the ongoing research and development of its pipeline of over-the-counter and prescription medications including its proprietary antiviral and "Liver Health" OTC formulations. In addition Caleco is developing Dermatological Products based on the active ingredients found in its proprietary formulation. Caleco's intellectual property covering the Liver Health formulations and derivatives consists of patent applications in the United States, Europe and Canada and four European Drug Master File applications.
Caleco's shares are traded in the United States on the OTC Bulletin Board (OTC.BB:CAEH - News) and in Germany on the Frankfurt Stock Exchange (Frankfurt:T3R - News)(WKN: A0N9Y0).
Pharmasset Initiates Dosing in a Combination Study of PSI-7977 and PSI-938 for Chronic Hepatitis C...
First study to look at a combination of of a purine and a pyrimidine nucleotide analog (PSI-938 and PSI-7977 respectively). Pharmasset believes the combination of two 'nucs' has a potential higher barrier to resistance, making it attractive to use in combo with other STAT-C/DAA drugs. The company plans a Phase II trail looking at the combination without interferon mid-2011 - Chris
- Phase 1 combination study of a pyrimidine (PSI-7977) and purine (PSI-938) nucleotide analog in patients with chronic hepatitis C
- Interim data expected in first quarter of 2011
PRINCETON, N.J., Nov. 30, 2010 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that dosing has begun in Part 2 of a Phase 1 study. This is the first clinical study combining a purine (PSI-938) and a pyrimidine (PSI-7977) nucleotide analog for HCV, and is designed to evaluate once daily doses of PSI-7977 and PSI-938 in patients with HCV who have not been treated previously.
"We are excited to be initiating this combination study with two proprietary nucleotide analogs for HCV," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "Based on our in vitro data, we believe the combination of two nucleotide analogs could provide potent antiviral activity across multiple HCV genotypes and could also have a higher barrier to resistance compared to other DAA combinations. We believe nucleotide analogs have a number of key attributes that may make them ideal partners for other DAA combinations, in addition to a 'nuc-nuc' combination."
About the Phase 1 Trial
In Part 1 of the Phase 1 multiple ascending dose study of PSI-938, suppression of HCV RNA below the limit of detection (LOD, <15 IU/mL) was observed in over half of the patients who received PSI-938 at daily doses of 200 mg or 300 mg for seven days. Part 2 of the study is designed to evaluate the combination of PSI-938 and PSI-7977. The primary objective is to assess the safety, tolerability and pharmacokinetics of PSI-938 administered alone for 14 days, and in combination with PSI-7977 for 7 to 14 days. The secondary objective is to evaluate viral kinetics of HCV RNA during monotherapy and combination nucleotide dosing. Approximately forty patients are expected to be enrolled into four cohorts as follows:
* PSI-938 QD administered as monotherapy for 14 days, followed by;
* PSI-938 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days and
* PSI-7977 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days, followed by;
* PSI-938 plus PSI-7977 QD for 14 days
We expect to report preliminary results from Part 2 of this Phase 1 study during the first quarter of calendar year 2011. We also expect to initiate a Phase 2 study of PSI-938 in combination with PSI-7977 during mid-2011. This Phase 2 study proposes to explore durations of PSI-938 and PSI-7977 in interferon-free combinations with an SVR endpoint.
- Phase 1 combination study of a pyrimidine (PSI-7977) and purine (PSI-938) nucleotide analog in patients with chronic hepatitis C
- Interim data expected in first quarter of 2011
PRINCETON, N.J., Nov. 30, 2010 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that dosing has begun in Part 2 of a Phase 1 study. This is the first clinical study combining a purine (PSI-938) and a pyrimidine (PSI-7977) nucleotide analog for HCV, and is designed to evaluate once daily doses of PSI-7977 and PSI-938 in patients with HCV who have not been treated previously.
"We are excited to be initiating this combination study with two proprietary nucleotide analogs for HCV," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "Based on our in vitro data, we believe the combination of two nucleotide analogs could provide potent antiviral activity across multiple HCV genotypes and could also have a higher barrier to resistance compared to other DAA combinations. We believe nucleotide analogs have a number of key attributes that may make them ideal partners for other DAA combinations, in addition to a 'nuc-nuc' combination."
About the Phase 1 Trial
In Part 1 of the Phase 1 multiple ascending dose study of PSI-938, suppression of HCV RNA below the limit of detection (LOD, <15 IU/mL) was observed in over half of the patients who received PSI-938 at daily doses of 200 mg or 300 mg for seven days. Part 2 of the study is designed to evaluate the combination of PSI-938 and PSI-7977. The primary objective is to assess the safety, tolerability and pharmacokinetics of PSI-938 administered alone for 14 days, and in combination with PSI-7977 for 7 to 14 days. The secondary objective is to evaluate viral kinetics of HCV RNA during monotherapy and combination nucleotide dosing. Approximately forty patients are expected to be enrolled into four cohorts as follows:
* PSI-938 QD administered as monotherapy for 14 days, followed by;
* PSI-938 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days and
* PSI-7977 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days, followed by;
* PSI-938 plus PSI-7977 QD for 14 days
We expect to report preliminary results from Part 2 of this Phase 1 study during the first quarter of calendar year 2011. We also expect to initiate a Phase 2 study of PSI-938 in combination with PSI-7977 during mid-2011. This Phase 2 study proposes to explore durations of PSI-938 and PSI-7977 in interferon-free combinations with an SVR endpoint.
Sunday, November 28, 2010
Avilla Therapeutics publishes paper on a new class of highly selective, irreversible HCV protease inhibitors
Publication in Nature Chemical Biology demonstrates that irreversible covalent inhibition can increase selectivity, potency and duration of action, broadens applications for targeted covalent drugs to the protease gene family
WALTHAM, MA – November 28, 2010 – Avila Therapeutics™, Inc., a biotechnology company developing novel targeted covalent drugs, has published research in Nature Chemical Biology demonstrating the first-ever selective irreversible inhibition of a viral protease using a targeted covalent drug. In the paper titled "Selective Irreversible Inhibition of a Protease by Targeting a Non-Catalytic Cysteine", Avila used its proprietary Avilomics™ platform to design covalent irreversible protease inhibitors that are highly selective, potent and with superior duration of action as compared to conventional protease inhibitors.
Importantly, the published research demonstrates that covalent drugs can be designed and targeted to irreversibly and covalently bond to molecular domains specific to proteases. This is the first report of the irreversible covalent approach being successfully extended to proteases, a very broad class of proteins that includes many important potential drug targets.
"This research elevates covalent drug design to a fundamentally new level," said Simon Campbell, PhD, CBE, FMedSci, FRS, a renowned scientist and former Senior Vice President for Worldwide Drug Discovery and Medicinal R&D Europe of Pfizer. "By creating extremely selective protease inhibitors with their platform, Avila is showing the remarkable therapeutic potential of irreversible covalent drugs to address a broad spectrum of drug targets."
"This publication showcases the creation of a whole new class of small molecule drugs," said Juswinder Singh, PhD, Chief Scientific Officer of Avila and a co-author of the paper. "This approach can make a difference to patients living with HCV infection, and we expect to make an impact in other important areas such as cancer and inflammatory disease."
In order to maximize selectivity and minimize off-target effects, the irreversible covalent inhibitors of HCV protease were designed to covalently target a unique structure in the HCV protease not found in human proteases. Key findings include:
* A representative irreversible covalent inhibitor designed, by Avila, was shown to inhibit the HCV protease (also known as "NS3") in cells at a concentration of 6 nM .
* Specific covalent bond formation between the drug and target protease was demonstrated through use of mass spectrometry and also x-ray crystallography.
* Very high selectivity of the Avila compounds was demonstrated by showing no notable inhibition of a panel of human proteases in biochemical assays with additional specificity demonstrated in cellular assays; this was contrasted experimentally with Telaprevir, an HCV protease inhibitor in late-stage clinical testing which demonstrated off-target biochemical activity against several human targets.
Avila has subsequently optimized additional drug candidates, yielding current development candidates, AVL-181 and AVL-192, which have excellent pharmacokinetics and bind potently to wild- type HCV protease as well as multiple genotypes and mutant forms of HCV protease.
###
About Avila Therapeutics™, Inc.
Avila focuses on design and development of targeted covalent drugs to achieve best-in class outcomes that cannot be achieved through traditional chemistries. This approach is called "protein silencing". The company's product pipeline has been built using its proprietary Avilomics™ platform and is currently focused on viral infection, cancer and autoimmune disease. Avila is funded by leading venture capital firms: Abingworth, Advent Venture Partners, Atlas Venture, Novartis Option Fund, and Polaris Venture Partners. For additional information, please visit http://www.avilatx.com
WALTHAM, MA – November 28, 2010 – Avila Therapeutics™, Inc., a biotechnology company developing novel targeted covalent drugs, has published research in Nature Chemical Biology demonstrating the first-ever selective irreversible inhibition of a viral protease using a targeted covalent drug. In the paper titled "Selective Irreversible Inhibition of a Protease by Targeting a Non-Catalytic Cysteine", Avila used its proprietary Avilomics™ platform to design covalent irreversible protease inhibitors that are highly selective, potent and with superior duration of action as compared to conventional protease inhibitors.
Importantly, the published research demonstrates that covalent drugs can be designed and targeted to irreversibly and covalently bond to molecular domains specific to proteases. This is the first report of the irreversible covalent approach being successfully extended to proteases, a very broad class of proteins that includes many important potential drug targets.
"This research elevates covalent drug design to a fundamentally new level," said Simon Campbell, PhD, CBE, FMedSci, FRS, a renowned scientist and former Senior Vice President for Worldwide Drug Discovery and Medicinal R&D Europe of Pfizer. "By creating extremely selective protease inhibitors with their platform, Avila is showing the remarkable therapeutic potential of irreversible covalent drugs to address a broad spectrum of drug targets."
"This publication showcases the creation of a whole new class of small molecule drugs," said Juswinder Singh, PhD, Chief Scientific Officer of Avila and a co-author of the paper. "This approach can make a difference to patients living with HCV infection, and we expect to make an impact in other important areas such as cancer and inflammatory disease."
In order to maximize selectivity and minimize off-target effects, the irreversible covalent inhibitors of HCV protease were designed to covalently target a unique structure in the HCV protease not found in human proteases. Key findings include:
* A representative irreversible covalent inhibitor designed, by Avila, was shown to inhibit the HCV protease (also known as "NS3") in cells at a concentration of 6 nM .
* Specific covalent bond formation between the drug and target protease was demonstrated through use of mass spectrometry and also x-ray crystallography.
* Very high selectivity of the Avila compounds was demonstrated by showing no notable inhibition of a panel of human proteases in biochemical assays with additional specificity demonstrated in cellular assays; this was contrasted experimentally with Telaprevir, an HCV protease inhibitor in late-stage clinical testing which demonstrated off-target biochemical activity against several human targets.
Avila has subsequently optimized additional drug candidates, yielding current development candidates, AVL-181 and AVL-192, which have excellent pharmacokinetics and bind potently to wild- type HCV protease as well as multiple genotypes and mutant forms of HCV protease.
###
About Avila Therapeutics™, Inc.
Avila focuses on design and development of targeted covalent drugs to achieve best-in class outcomes that cannot be achieved through traditional chemistries. This approach is called "protein silencing". The company's product pipeline has been built using its proprietary Avilomics™ platform and is currently focused on viral infection, cancer and autoimmune disease. Avila is funded by leading venture capital firms: Abingworth, Advent Venture Partners, Atlas Venture, Novartis Option Fund, and Polaris Venture Partners. For additional information, please visit http://www.avilatx.com
Friday, November 26, 2010
Clinical Care Options AASLD 2010 Highlights slide deck ready for download...
Robert G. Gish, MD, and Stephen A. Harrison, MD, FACP, review the most clinically relevant data from this important annual meeting. Registration required. You can download them here.
Tuesday, November 23, 2010
Roche severs HCV treatment collaboration and license agreement between with Ligand Pharma...
Drug giant Roche terminates it's treatment collaboration and license agreement with Ligand Pharma. Ligand gets a good deal, with non-exclusive, worldwide, royalty-bearing license under specified Roche patents to develop, make and sell related compounds and products, subject to royalty payments on net sales. Roche, on the other hand, is prohibited for ten years following the termination from developing or commercializing related compounds. Maybe the InterMune deal was enough? Nah. Has to be some other reason.
Tue, Nov 23 2010
* Says received a notice from Roche unit on Nov 19
* Roche prohibited to develop related compounds for 10 yrs
* Shares down 1 pct after-the-bell
Nov 23 (Reuters) - Ligand Pharmaceuticals Inc (LGNDD.O: Quote, Profile, Research) said Swiss drugmaker Roche Holding AG (ROG.VX: Quote, Profile, Research) was exercising its right to terminate the collaboration and license agreement between the two companies on developing hepatitis C treatment.
The collaboration and license agreement with Roche began in 2008 to develop new treatments for hepatitis C viral infection using liver-targeting technology.
In April, Ligand received $6.5 million milestone payment from Roche.
As per the agreement, Ligand will receive a non-exclusive, worldwide, royalty-bearing license under specified Roche patents to develop, make and sell related compounds and products, subject to royalty payments on net sales.
Roche will be prohibited for ten years following the termination from developing or commercializing related compounds, Ligand said in a regulatory filing.
Ligand said it received a notice from Roche units last Friday regarding the termination.
Ligand's shares, which have lost about 18 percent since the company got Japanese marketing nod for its blood clotting treatment earlier this month, were trading down about 1 percent at $8.16 Tuesday after-the-bell.
Tue, Nov 23 2010
* Says received a notice from Roche unit on Nov 19
* Roche prohibited to develop related compounds for 10 yrs
* Shares down 1 pct after-the-bell
Nov 23 (Reuters) - Ligand Pharmaceuticals Inc (LGNDD.O: Quote, Profile, Research) said Swiss drugmaker Roche Holding AG (ROG.VX: Quote, Profile, Research) was exercising its right to terminate the collaboration and license agreement between the two companies on developing hepatitis C treatment.
The collaboration and license agreement with Roche began in 2008 to develop new treatments for hepatitis C viral infection using liver-targeting technology.
In April, Ligand received $6.5 million milestone payment from Roche.
As per the agreement, Ligand will receive a non-exclusive, worldwide, royalty-bearing license under specified Roche patents to develop, make and sell related compounds and products, subject to royalty payments on net sales.
Roche will be prohibited for ten years following the termination from developing or commercializing related compounds, Ligand said in a regulatory filing.
Ligand said it received a notice from Roche units last Friday regarding the termination.
Ligand's shares, which have lost about 18 percent since the company got Japanese marketing nod for its blood clotting treatment earlier this month, were trading down about 1 percent at $8.16 Tuesday after-the-bell.
Roche severs HCV treatment collaboration and license agreement between with Ligand Pharma...
Drug giant Roche terminates it's treatment collaboration and license agreement with Ligand Pharma. Ligand gets a good deal, with non-exclusive, worldwide, royalty-bearing license under specified Roche patents to develop, make and sell related compounds and products, subject to royalty payments on net sales. Roche, on the other hand, is prohibited for ten years following the termination from developing or commercializing related compounds. Maybe the InterMune deal was enough? Nah. Has to be some other reason.
Tue, Nov 23 2010
* Says received a notice from Roche unit on Nov 19
* Roche prohibited to develop related compounds for 10 yrs
* Shares down 1 pct after-the-bell
Nov 23 (Reuters) - Ligand Pharmaceuticals Inc (LGNDD.O: Quote, Profile, Research) said Swiss drugmaker Roche Holding AG (ROG.VX: Quote, Profile, Research) was exercising its right to terminate the collaboration and license agreement between the two companies on developing hepatitis C treatment.
The collaboration and license agreement with Roche began in 2008 to develop new treatments for hepatitis C viral infection using liver-targeting technology.
In April, Ligand received $6.5 million milestone payment from Roche.
As per the agreement, Ligand will receive a non-exclusive, worldwide, royalty-bearing license under specified Roche patents to develop, make and sell related compounds and products, subject to royalty payments on net sales.
Roche will be prohibited for ten years following the termination from developing or commercializing related compounds, Ligand said in a regulatory filing.
Ligand said it received a notice from Roche units last Friday regarding the termination.
Ligand's shares, which have lost about 18 percent since the company got Japanese marketing nod for its blood clotting treatment earlier this month, were trading down about 1 percent at $8.16 Tuesday after-the-bell.
Tue, Nov 23 2010
* Says received a notice from Roche unit on Nov 19
* Roche prohibited to develop related compounds for 10 yrs
* Shares down 1 pct after-the-bell
Nov 23 (Reuters) - Ligand Pharmaceuticals Inc (LGNDD.O: Quote, Profile, Research) said Swiss drugmaker Roche Holding AG (ROG.VX: Quote, Profile, Research) was exercising its right to terminate the collaboration and license agreement between the two companies on developing hepatitis C treatment.
The collaboration and license agreement with Roche began in 2008 to develop new treatments for hepatitis C viral infection using liver-targeting technology.
In April, Ligand received $6.5 million milestone payment from Roche.
As per the agreement, Ligand will receive a non-exclusive, worldwide, royalty-bearing license under specified Roche patents to develop, make and sell related compounds and products, subject to royalty payments on net sales.
Roche will be prohibited for ten years following the termination from developing or commercializing related compounds, Ligand said in a regulatory filing.
Ligand said it received a notice from Roche units last Friday regarding the termination.
Ligand's shares, which have lost about 18 percent since the company got Japanese marketing nod for its blood clotting treatment earlier this month, were trading down about 1 percent at $8.16 Tuesday after-the-bell.
Vertex files NDA for Telaprevir, requests 6 month priority review....
CAMBRIDGE, Mass., Nov 23, 2010 (BUSINESS WIRE) -- --- Six-Month Priority Review Requested -
Vertex Pharmaceuticals Incorporated announced today that it has completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval for telaprevir, Vertex's investigational treatment for people with hepatitis C. The NDA submission is supported by results from three Phase 3 studies, ADVANCE, ILLUMINATE and REALIZE, which evaluated telaprevir in people chronically infected with genotype 1 hepatitis C virus (HCV) who were new to treatment as well as those who were treated before but did not achieve a sustained viral response (SVR, or viral cure). The submission includes a request for Priority Review, which would reduce the FDA's review time from 10 months to six months. The FDA grants Priority Review status for several reasons, including if the medicine is considered a major advance in treatment.
"This submission is a milestone in our more than 15-year effort to change the way hepatitis C is treated," said Matthew Emmens, Chairman, President and Chief Executive Officer of Vertex. "We are committed to working closely with the FDA to make telaprevir available as quickly as possible to the millions of people with hepatitis C who need new medicines to increase their chances for a viral cure."
Highlights of the Telaprevir Phase 3 Data Included in the Submission
All Phase 3 studies met their primary endpoints and results below are from the treatment arms where telaprevir was started immediately in combination with pegylated-interferon and ribavirin for the first 12 weeks of treatment.
In people with hepatitis C who were new to treatment (treatment-naive):
Up to 75% achieved a viral cure with telaprevir-based combination therapy, compared to 44% of people who received pegylated-interferon and ribavirin alone; A majority (58% in ADVANCE and 65% in ILLUMINATE) were eligible to reduce their treatment time by half -- from 48 weeks to 24 weeks; and Data showed there was no benefit to extending total treatment from 24 weeks to 48 weeks in people whose virus was undetectable at weeks 4 and 12 with telaprevir-based therapy.
In the three major subgroups of people with hepatitis C who had not achieved a viral cure with a prior course of treatment (treatment-experienced):
83% of prior relapsers, 59% of prior partial responders and 29% of prior null responders achieved a viral cure with telaprevir-based combination therapy compared to 24%, 15%, and 5% of people in these subgroups, respectively, who received pegylated-interferon and ribavirin alone. These results were achieved with a simultaneous start of all three drugs for the first 12 weeks followed by pegylated-interferon and ribavirin alone for an additional 36 weeks.
The safety and tolerability results of telaprevir-based combination therapy were consistent across the Phase 3 studies. The most common adverse events regardless of treatment arm were rash, fatigue, pruritis, headache, nausea, anemia, insomnia, diarrhea, flu-like symptoms and pyrexia, with the majority being mild or moderate in severity.
More Effective Therapies Needed to Improve Viral Cure Rates
Hepatitis C is a serious disease, typically without symptoms, which affects up to 3.9 million people in the United States. Hepatitis C can lead to scarring of the liver (cirrhosis), resulting in liver failure, liver cancer and the need for liver transplantation. Approved medicines for people with genotype 1 hepatitis C are given for a year, and less than half of people treated with these therapies achieve a viral cure.(4,5,6) Telaprevir is an investigational, oral inhibitor that acts directly on the HCV protease, an enzyme essential for viral replication. To date, more than 2,500 people with genotype 1 hepatitis C have received telaprevir in Phase 2 and Phase 3 studies.
"In our trials, starting patients with 12 weeks of telaprevir-based combination therapy significantly improved viral cure rates compared to treatment with currently approved medicines, even in groups of people considered the most difficult to treat," said Peter Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of Global Research and Development at Vertex. "We're also encouraged by telaprevir data that showed most patients new to therapy were able to achieve high viral cure rates and reduce their total treatment time by half."
Vertex is developing telaprevir in collaboration with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America and Tibotec has rights in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
Vertex was granted Fast Track designation by the FDA for telaprevir in 2005. In mid-2010, as part of the Fast Track designation, Vertex began to submit completed sections of the NDA for review by the FDA on a rolling basis rather than wait until every section of the application was complete.
Data from Phase 3 Studies in All Major Patient Types, Including the Most Difficult-to-Treat
The Phase 3 studies evaluated people with genotype 1 hepatitis C who were new to treatment as well as those who had previously received treatment but did not achieve a cure, including people who have traditionally responded poorly to approved medicines. In Phase 3 studies, telaprevir was given to people three times a day in combination with pegylated-interferon and ribavirin for the first 12 weeks of therapy followed by either 12 weeks or 36 weeks of Pegasys(R) (pegylated-interferon alfa-2a) and Copegus(R) (ribavirin) alone for a total treatment time of either 24 weeks or 48 weeks. The ability to shorten treatment time from 48 weeks to 24 weeks for people new to treatment was based on their response to therapy at weeks 4 and 12. People who did not achieve a viral cure with a prior course of therapy received a total of 48 weeks of treatment. In October 2010, Vertex announced the start of a Phase 3 study to evaluate twice-daily (BID) dosing of a telaprevir-based combination regimen.
ADVANCE: Pivotal study in 1,095 people who were new to treatment
The primary endpoint of ADVANCE was SVR, defined as the proportion of people who had undetectable viral load (HCV RNA) both at the end of treatment and 24 weeks after the end of treatment. The secondary endpoint was to evaluate the safety of telaprevir when dosed in combination with pegylated-interferon and ribavirin. ADVANCE also evaluated the ability to reduce total treatment time by half -- from 48 weeks to 24 weeks, which was guided by a patient's response to therapy (undetectable viral load at weeks 4 and 12).
ILLUMINATE: Supplemental study in 540 people to evaluate shorter treatment durations in people who were new to treatment
The primary endpoint of the study was SVR in two telaprevir-based treatment arms of people whose virus was undetectable at week 4 and week 12 of treatment (eRVR, extended rapid viral response). These patients were randomized to either 24 weeks or 48 weeks of total therapy. ILLUMINATE was designed to evaluate whether there was any benefit to extending therapy from 24 weeks to 48 weeks in people who met these criteria. There was no control arm of pegylated-interferon and ribavirin alone in the study.
In both the ADVANCE and ILLUMINATE studies, telaprevir-based combination therapy also resulted in improved SVR rates in various subgroups of people with characteristics known to limit response to approved medicines such as race/ethnicity or stage of liver fibrosis. Data from these studies were presented in November 2010 at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
REALIZE: Pivotal study in 662 people who did not achieve a viral cure with previous therapy
The primary endpoint of the study was SVR in each of the two telaprevir treatment arms compared to the control arm, and for the three subgroups of people included in the study. REALIZE is the only Phase 3 study to date of a direct-acting antiviral medicine to include all three major subgroups of people with hepatitis C who did not achieve a viral cure with a previous course of therapy:
Relapser: defined as a person whose hepatitis C virus was undetectable at the completion of at least 42 weeks of a prior course of therapy but whose virus became detectable during the follow-up period; Partial Responder: defined as a person who achieved at least a 2 log10 (100 times) reduction in viral load (HCV RNA) at week 12, but whose hepatitis C virus never became undetectable by week 24 of a prior course of therapy; and Null Responder: defined as a person who experienced a less than 2 log10 drop in viral load at week 12 of a prior course of therapy.
In REALIZE, people received 48 weeks of total therapy, which included 12 weeks of telaprevir combined with pegylated-interferon and ribavirin. One of the telaprevir treatment arms was designed to evaluate, for the first time, whether viral cure rates could be further improved by starting pegylated-interferon and ribavirin alone for the first four weeks of treatment (delayed start) compared to a simultaneous start of telaprevir in combination with these medicines. There was no clinical benefit observed with the telaprevir delayed-start treatment arm in any of the subgroups of patients compared to the simultaneous-start arm. Final results from REALIZE, including safety and efficacy data, will be presented at an upcoming medical meeting.
Safety and Tolerability Information for ADVANCE, ILLUMINATE and REALIZE
The safety and tolerability results of telaprevir-based combination regimens were consistent across the Phase 3 studies. The most common adverse events (AEs) were rash, fatigue, pruritis, headache, nausea, anemia, insomnia, diarrhea, flu-like symptoms and pyrexia with the majority being mild or moderate in severity. Rash and anemia occurred more frequently in the telaprevir treatment arms compared to the control arms.
Rash was primarily characterized as eczema-like, manageable and resolved upon stopping telaprevir. More than 90% of rash was mild to moderate and was primarily managed with the use of topical corticosteroids and antihistamines. Anemia was primarily managed by reducing the dose of ribavirin. Erythropoiesis-stimulating agents (ESAs) were used in only 1% of people in the Phase 2 and Phase 3 studies. Discontinuation of all drugs due to either rash or anemia during the telaprevir/placebo treatment phase was 1% to 3% in the telaprevir treatment arms.
Vertex Pharmaceuticals Incorporated announced today that it has completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval for telaprevir, Vertex's investigational treatment for people with hepatitis C. The NDA submission is supported by results from three Phase 3 studies, ADVANCE, ILLUMINATE and REALIZE, which evaluated telaprevir in people chronically infected with genotype 1 hepatitis C virus (HCV) who were new to treatment as well as those who were treated before but did not achieve a sustained viral response (SVR, or viral cure). The submission includes a request for Priority Review, which would reduce the FDA's review time from 10 months to six months. The FDA grants Priority Review status for several reasons, including if the medicine is considered a major advance in treatment.
"This submission is a milestone in our more than 15-year effort to change the way hepatitis C is treated," said Matthew Emmens, Chairman, President and Chief Executive Officer of Vertex. "We are committed to working closely with the FDA to make telaprevir available as quickly as possible to the millions of people with hepatitis C who need new medicines to increase their chances for a viral cure."
Highlights of the Telaprevir Phase 3 Data Included in the Submission
All Phase 3 studies met their primary endpoints and results below are from the treatment arms where telaprevir was started immediately in combination with pegylated-interferon and ribavirin for the first 12 weeks of treatment.
In people with hepatitis C who were new to treatment (treatment-naive):
Up to 75% achieved a viral cure with telaprevir-based combination therapy, compared to 44% of people who received pegylated-interferon and ribavirin alone; A majority (58% in ADVANCE and 65% in ILLUMINATE) were eligible to reduce their treatment time by half -- from 48 weeks to 24 weeks; and Data showed there was no benefit to extending total treatment from 24 weeks to 48 weeks in people whose virus was undetectable at weeks 4 and 12 with telaprevir-based therapy.
In the three major subgroups of people with hepatitis C who had not achieved a viral cure with a prior course of treatment (treatment-experienced):
83% of prior relapsers, 59% of prior partial responders and 29% of prior null responders achieved a viral cure with telaprevir-based combination therapy compared to 24%, 15%, and 5% of people in these subgroups, respectively, who received pegylated-interferon and ribavirin alone. These results were achieved with a simultaneous start of all three drugs for the first 12 weeks followed by pegylated-interferon and ribavirin alone for an additional 36 weeks.
The safety and tolerability results of telaprevir-based combination therapy were consistent across the Phase 3 studies. The most common adverse events regardless of treatment arm were rash, fatigue, pruritis, headache, nausea, anemia, insomnia, diarrhea, flu-like symptoms and pyrexia, with the majority being mild or moderate in severity.
More Effective Therapies Needed to Improve Viral Cure Rates
Hepatitis C is a serious disease, typically without symptoms, which affects up to 3.9 million people in the United States. Hepatitis C can lead to scarring of the liver (cirrhosis), resulting in liver failure, liver cancer and the need for liver transplantation. Approved medicines for people with genotype 1 hepatitis C are given for a year, and less than half of people treated with these therapies achieve a viral cure.(4,5,6) Telaprevir is an investigational, oral inhibitor that acts directly on the HCV protease, an enzyme essential for viral replication. To date, more than 2,500 people with genotype 1 hepatitis C have received telaprevir in Phase 2 and Phase 3 studies.
"In our trials, starting patients with 12 weeks of telaprevir-based combination therapy significantly improved viral cure rates compared to treatment with currently approved medicines, even in groups of people considered the most difficult to treat," said Peter Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of Global Research and Development at Vertex. "We're also encouraged by telaprevir data that showed most patients new to therapy were able to achieve high viral cure rates and reduce their total treatment time by half."
Vertex is developing telaprevir in collaboration with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America and Tibotec has rights in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
Vertex was granted Fast Track designation by the FDA for telaprevir in 2005. In mid-2010, as part of the Fast Track designation, Vertex began to submit completed sections of the NDA for review by the FDA on a rolling basis rather than wait until every section of the application was complete.
Data from Phase 3 Studies in All Major Patient Types, Including the Most Difficult-to-Treat
The Phase 3 studies evaluated people with genotype 1 hepatitis C who were new to treatment as well as those who had previously received treatment but did not achieve a cure, including people who have traditionally responded poorly to approved medicines. In Phase 3 studies, telaprevir was given to people three times a day in combination with pegylated-interferon and ribavirin for the first 12 weeks of therapy followed by either 12 weeks or 36 weeks of Pegasys(R) (pegylated-interferon alfa-2a) and Copegus(R) (ribavirin) alone for a total treatment time of either 24 weeks or 48 weeks. The ability to shorten treatment time from 48 weeks to 24 weeks for people new to treatment was based on their response to therapy at weeks 4 and 12. People who did not achieve a viral cure with a prior course of therapy received a total of 48 weeks of treatment. In October 2010, Vertex announced the start of a Phase 3 study to evaluate twice-daily (BID) dosing of a telaprevir-based combination regimen.
ADVANCE: Pivotal study in 1,095 people who were new to treatment
The primary endpoint of ADVANCE was SVR, defined as the proportion of people who had undetectable viral load (HCV RNA) both at the end of treatment and 24 weeks after the end of treatment. The secondary endpoint was to evaluate the safety of telaprevir when dosed in combination with pegylated-interferon and ribavirin. ADVANCE also evaluated the ability to reduce total treatment time by half -- from 48 weeks to 24 weeks, which was guided by a patient's response to therapy (undetectable viral load at weeks 4 and 12).
ILLUMINATE: Supplemental study in 540 people to evaluate shorter treatment durations in people who were new to treatment
The primary endpoint of the study was SVR in two telaprevir-based treatment arms of people whose virus was undetectable at week 4 and week 12 of treatment (eRVR, extended rapid viral response). These patients were randomized to either 24 weeks or 48 weeks of total therapy. ILLUMINATE was designed to evaluate whether there was any benefit to extending therapy from 24 weeks to 48 weeks in people who met these criteria. There was no control arm of pegylated-interferon and ribavirin alone in the study.
In both the ADVANCE and ILLUMINATE studies, telaprevir-based combination therapy also resulted in improved SVR rates in various subgroups of people with characteristics known to limit response to approved medicines such as race/ethnicity or stage of liver fibrosis. Data from these studies were presented in November 2010 at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
REALIZE: Pivotal study in 662 people who did not achieve a viral cure with previous therapy
The primary endpoint of the study was SVR in each of the two telaprevir treatment arms compared to the control arm, and for the three subgroups of people included in the study. REALIZE is the only Phase 3 study to date of a direct-acting antiviral medicine to include all three major subgroups of people with hepatitis C who did not achieve a viral cure with a previous course of therapy:
Relapser: defined as a person whose hepatitis C virus was undetectable at the completion of at least 42 weeks of a prior course of therapy but whose virus became detectable during the follow-up period; Partial Responder: defined as a person who achieved at least a 2 log10 (100 times) reduction in viral load (HCV RNA) at week 12, but whose hepatitis C virus never became undetectable by week 24 of a prior course of therapy; and Null Responder: defined as a person who experienced a less than 2 log10 drop in viral load at week 12 of a prior course of therapy.
In REALIZE, people received 48 weeks of total therapy, which included 12 weeks of telaprevir combined with pegylated-interferon and ribavirin. One of the telaprevir treatment arms was designed to evaluate, for the first time, whether viral cure rates could be further improved by starting pegylated-interferon and ribavirin alone for the first four weeks of treatment (delayed start) compared to a simultaneous start of telaprevir in combination with these medicines. There was no clinical benefit observed with the telaprevir delayed-start treatment arm in any of the subgroups of patients compared to the simultaneous-start arm. Final results from REALIZE, including safety and efficacy data, will be presented at an upcoming medical meeting.
Safety and Tolerability Information for ADVANCE, ILLUMINATE and REALIZE
The safety and tolerability results of telaprevir-based combination regimens were consistent across the Phase 3 studies. The most common adverse events (AEs) were rash, fatigue, pruritis, headache, nausea, anemia, insomnia, diarrhea, flu-like symptoms and pyrexia with the majority being mild or moderate in severity. Rash and anemia occurred more frequently in the telaprevir treatment arms compared to the control arms.
Rash was primarily characterized as eczema-like, manageable and resolved upon stopping telaprevir. More than 90% of rash was mild to moderate and was primarily managed with the use of topical corticosteroids and antihistamines. Anemia was primarily managed by reducing the dose of ribavirin. Erythropoiesis-stimulating agents (ESAs) were used in only 1% of people in the Phase 2 and Phase 3 studies. Discontinuation of all drugs due to either rash or anemia during the telaprevir/placebo treatment phase was 1% to 3% in the telaprevir treatment arms.
Monday, November 22, 2010
Clinical Care Options 2011 HIV & Hepatitis C Symposium...
2011 Annual CCO
HIV and Hepatitis C Symposium:
A Unique Program Integrating New Advances and Treatment Strategies in HIV, HCV, and Coinfection
June 9-12, 2011: Washington, DC
Mark your calendar today!
CCO has combined our 2 outstanding annual update symposia to provide a unique new meeting that addresses both the separate concerns of HCV and HIV treaters, as well as the intersection between these fields.
The program has been carefully structured to make it easy for participants to choose to attend the entire meeting or just the HIV or HCV sessions. Whether you treat only HIV, only HCV, or both, the flexibility of the program allows you to attend the sessions that are right for you.
A full day will address the latest issues in HIV management, including antiretroviral strategies, the management of comorbidities, and the emerging clinical role of pre-exposure prophylaxis.
Another full day of state-of-the-art educational content will address the clinical role of the new HCV agents that are expected to enter the clinic in 2011, including plenary reviews, roundtable discussions, and case-based learning.
Finally, a unique half-day session will explore the intersection between the epidemics, including management of coinfection, using the new HCV drugs in patients receiving antiretroviral therapy, and lessons the 2 fields are learning from each other.
Full Agenda and Online Registration Coming Soon
If you have any advance questions, please reply to this message or send an email to memberservices@clinicaloptions.com.
HIV and Hepatitis C Symposium:
A Unique Program Integrating New Advances and Treatment Strategies in HIV, HCV, and Coinfection
June 9-12, 2011: Washington, DC
Mark your calendar today!
CCO has combined our 2 outstanding annual update symposia to provide a unique new meeting that addresses both the separate concerns of HCV and HIV treaters, as well as the intersection between these fields.
The program has been carefully structured to make it easy for participants to choose to attend the entire meeting or just the HIV or HCV sessions. Whether you treat only HIV, only HCV, or both, the flexibility of the program allows you to attend the sessions that are right for you.
A full day will address the latest issues in HIV management, including antiretroviral strategies, the management of comorbidities, and the emerging clinical role of pre-exposure prophylaxis.
Another full day of state-of-the-art educational content will address the clinical role of the new HCV agents that are expected to enter the clinic in 2011, including plenary reviews, roundtable discussions, and case-based learning.
Finally, a unique half-day session will explore the intersection between the epidemics, including management of coinfection, using the new HCV drugs in patients receiving antiretroviral therapy, and lessons the 2 fields are learning from each other.
Full Agenda and Online Registration Coming Soon
If you have any advance questions, please reply to this message or send an email to memberservices@clinicaloptions.com.
Electronic patient diaries vs on-site side-effect reports: A case study featuring Locteron
Very nice article here on the power of ePRO (Electronic patient diaries) vs on-site patient reports to the physician on adverse events. It appears that evolving technology is helping to undermine the incidence of under-reporting of adverse events. This particular example adds credibility to Biolex's Locteron (Interferon Lambda) Phase IIb trial.
Biolex reveals ePRO surprise; selection process
By George Miller
Created Nov 22 2010 - 1:32am
Biolex CEO Jan Turek notes something unforeseen in the ePRO element of the company's recent trial of a hepatitis C treatment: The degree of difference in reports of side-effect severity in the weekly case report forms completed by clinicians versus the daily ePRO accounts of trial volunteers. Some 85 percent of reports by doctors describe mild side-effects, whereas the volunteers reporting electronically most often rated the severity as moderate or severe.
It was "a surprise to us and our key opinion leaders," Turek says in a phone interview. "It brought home the need for patient reports to be taken more seriously."
Findings from the trial do, however, reflect commonality between the reporting media types in the trial's side-effect result--a statistically significant 40 to 50 percent drop in the frequency and severity of flu-like symptoms for the 480-microgram dose of Biolex's Locteron compared with the PEG-Intron control.
Researchers were tracking the flu-like symptoms as a means of comparing the treatments in the Phase IIb trial. "What you measure drives how you gather data," explains Biolex CFO Dale Sander in the interview. Investigators as well as the key opinion leaders thought ePRO fit the bill. The side-effect data collected through the ePRO system are considered supplemental to the reports taken during weekly clinic visits.
Biolex used an ePRO system from Unithink [1] in the global trial. Among the key factors in its choice was the system's ability to instantaneously receive reports and capture them in the EDC system, rather than a set-up that involves reporting and later docking and uploading, says Amy Rigney, clinical ops director. "That was a differentiator."
Another was ease of patient use. "We wanted to be sure the ePRO system was programmed for several languages." Also, ePRO/EDC set-up allowed trial volunteers to report side effects via cellphone or laptop. "It didn't force the issue one way or the other," she says.
Biolex evaluated available ePRO systems in 2008 and had several months of discussions involving investigators, the data management group, and the clinical group. The company's IT team participated throughout the process to ensure overall systems compatibility, says Rigney, including the final selection of Unithink.
"Volunteers' recall and ability to assess a side effect is better when they are entering the data simultaneous with the event," she says. "You're getting it unfiltered."
Biolex reveals ePRO surprise; selection process
By George Miller
Created Nov 22 2010 - 1:32am
Biolex CEO Jan Turek notes something unforeseen in the ePRO element of the company's recent trial of a hepatitis C treatment: The degree of difference in reports of side-effect severity in the weekly case report forms completed by clinicians versus the daily ePRO accounts of trial volunteers. Some 85 percent of reports by doctors describe mild side-effects, whereas the volunteers reporting electronically most often rated the severity as moderate or severe.
It was "a surprise to us and our key opinion leaders," Turek says in a phone interview. "It brought home the need for patient reports to be taken more seriously."
Findings from the trial do, however, reflect commonality between the reporting media types in the trial's side-effect result--a statistically significant 40 to 50 percent drop in the frequency and severity of flu-like symptoms for the 480-microgram dose of Biolex's Locteron compared with the PEG-Intron control.
Researchers were tracking the flu-like symptoms as a means of comparing the treatments in the Phase IIb trial. "What you measure drives how you gather data," explains Biolex CFO Dale Sander in the interview. Investigators as well as the key opinion leaders thought ePRO fit the bill. The side-effect data collected through the ePRO system are considered supplemental to the reports taken during weekly clinic visits.
Biolex used an ePRO system from Unithink [1] in the global trial. Among the key factors in its choice was the system's ability to instantaneously receive reports and capture them in the EDC system, rather than a set-up that involves reporting and later docking and uploading, says Amy Rigney, clinical ops director. "That was a differentiator."
Another was ease of patient use. "We wanted to be sure the ePRO system was programmed for several languages." Also, ePRO/EDC set-up allowed trial volunteers to report side effects via cellphone or laptop. "It didn't force the issue one way or the other," she says.
Biolex evaluated available ePRO systems in 2008 and had several months of discussions involving investigators, the data management group, and the clinical group. The company's IT team participated throughout the process to ensure overall systems compatibility, says Rigney, including the final selection of Unithink.
"Volunteers' recall and ability to assess a side effect is better when they are entering the data simultaneous with the event," she says. "You're getting it unfiltered."
Sunday, November 21, 2010
Phase II results of Gilead's GS 9190 & GS 9256 in combo with SOC....
Missed this during AASLD for some reason. Gilead has a big commitment to HCV, bringing in HCV thought leader heavy-weight/clinical research mogul John McHutchison, MD, from Duke as Senior Vice President, Liver Disease Therapeutics. They now boast seven unique molecules spanning six therapeutic classes with different mechanisms of action, five of which are in clinical trials and two going in to the clinic in '11. As for the Phase II trial presented as a late breaker oral session at AASLD, GS 9190 and GS 9256 look very good from an efficacy and tolerability standpoint. It's pretty clear that Peg-INF and especially Ribavirin aren't going anywhere. This should make the folks at Three Rivers/Kadmon pretty happy given that they've cornered the both the current and future branded Ribavirin market at a time when pill count and tolerability are going to be a huge factor for STAT-C therapy. Can't hurt the prospects for Locteron either. - Chris
Gilead's Investigational Hepatitis C Compounds GS 9190 and GS 9256 in Combination with Standard of Care Therapies Achieve Substantial Viral Suppression in Phase II Study
-- Compounds Among the Company's Seven HCV Pipeline Candidates Spanning Six Therapeutic Classes --
BOSTON, Oct 30, 2010 (BUSINESS WIRE) -- Gilead Sciences, Inc today announced data from a Phase IIa study showing that its investigational compounds GS 9190 and GS 9256, used in conjunction with current standard of care therapies, produced substantial suppression of the hepatitis C virus (HCV) within 28 days of treatment. The findings are being presented Monday, November 1, during a latebreaker oral session (#LB-1) at the 61st annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2010) in Boston.
"Patients with chronic hepatitis C urgently need new and better treatment options, particularly combination therapies involving antiviral drugs that employ multiple mechanisms of action to eradicate the virus," said the study's principal investigator, Stefan Zeuzem, MD, JW Goethe University Hospital, Frankfurt, Germany. "The data presented today support the continued clinical evaluation of GS 9190 and GS 9256 in combination with other hepatitis C therapies and provide additional clinical insight into the effect of ribavirin in the absence of interferon."
More than seven million people in industrialized countries are chronically infected with HCV, and as many as three million Americans have the disease. The current standard of care in HCV therapy is the oral antiviral ribavirin (RBV), administered in combination with peg-interferon (Peg-IFN), which is delivered via injection and achieves a sustained therapeutic response in only 40-55 percent of patients with HCV genotype 1, the most common form of HCV in the Americas and Europe.(1)
Gilead's three-arm Phase IIa trial (Study 196-0112) evaluated the safety and efficacy of GS 9190, an oral polymerase inhibitor, in combination with GS 9256, an oral protease inhibitor, when used as: 1) a dual antiviral therapy alone; 2) a three-drug regimen with RBV; or 3) a four-drug regimen with RBV and Peg-IFN. The study found that the all-oral regimen of GS 9190, GS 9256 and RBV produced substantial viral suppression, with a median maximal decline from baseline in HCV RNA of 5.1 log10 IU/mL during 28 days of treatment. Among patients given the four-drug regimen of GS 9190, GS 9256, RBV and Peg-IFN, 100 percent (14/14 patients) achieved Rapid Virologic Response (RVR) (HCV RNA < 25 IU/mL) at day 28, with 93 percent (13/14 patients) achieving undetectable viral levels (HCV RNA < 10 IU/mL). No virologic breakthroughs were observed in this arm.
"Oral combinations of multiple antiviral agents are expected to become the new standard of care for patients with hepatitis C, and our ultimate goal and vision is to develop a potent and well-tolerated fixed-dose combination product that will eliminate the need for peg-interferon," said John McHutchison, MD, Senior Vice President for Liver Disease Therapeutics at Gilead. "These data strongly support the clinical potential of this oral combination HCV therapy, and we're looking forward to advancing the development of GS 9190 and GS 9256."
About Study 196-0112
This Phase IIa, randomized, open-label trial is evaluating GS 9190 and GS 9256 in combination (n=16), and with RBV (n=15) or with RBV/Peg-IFN (n=15). The trial enrolled treatment-naive adults with chronic HCV genotype 1 for a 28-day course of treatment. The primary outcome measures of the trial are the percentage of subjects achieving RVR, defined as HCV RNA < 25 IU/mL at Day 28, as well as the incidence of treatment-related side effects and adverse events.
Patients in the two-drug arm of the study received GS 9190 (40 mg twice daily) and GS 9256 (75 mg twice daily). Patients in the three-drug arm received a regimen of GS 9190, GS 9256 and RBV (1,000-1,200 mg total daily dose, administered twice daily), and patients in the four-drug arm also received Peg-IFN (180 g, injected once per week). In the final analysis, one patient in the four-drug arm was excluded due to a protocol violation. A median maximal decline from baseline HCV RNA of 4.1 log10 IU/mL was observed in patients receiving the two-drug combination of GS 9190 and GS 9256. The addition of RBV and RBV/Peg-IFN enhanced these responses, with median maximal RNA declines of 5.1 log10 IU/mL and 5.7 log10 IU/mL, respectively.
GS 9190 and GS 9256 were generally well tolerated. The majority of adverse events were Grade 1 or 2 in severity and resolved with continued treatment. The most common adverse events observed in each of the three arms were headache, diarrhea and nausea. Some patients taking the three-drug combination also experienced fatigue and insomnia, and some patients taking the four-drug combination experienced influenza-like illness, fatigue, myalgia and cough. There were two serious adverse events including one case of bursitis and a hospitalization for vasovagal collapse (fainting), which was attributed to gastroenteritis and occurred in a patient who continued therapy and achieved RVR. Elevations in bilirubin were observed across all three study arms, the majority of which were Grade 1 or 2 in severity and none of which resulted in study drug discontinuation.
Additional Gilead HCV Pipeline Research
In addition to Study 196-0112, data from seven additional studies will be presented at The Liver Meeting highlighting the clinical profile of the company's other HCV pipeline candidates, including another protease inhibitor, GS 9451, and a novel NS5A inhibitor, GS 5885. Gilead's HCV pipeline now includes seven unique molecules spanning six therapeutic classes with different mechanisms of action. Five of these compounds are currently in clinical trials, and two are slated to enter human clinical studies early next year.
In a Phase I three-day dose-ranging study (Study 169-0103), GS 9451 was found to be highly potent in terms of anti-HCV activity and demonstrated a long plasma half-life with once-daily dosing potential (Abstract #820). GS 9451 was tested among 33 patients with HCV genotype 1a (GT1a) or 1b (GT1b). GT1a patients received GS 9451 at 60 mg, 200 mg and 400 mg once-daily doses, and the median maximal decline from baseline in HCV RNA was 0.88, 3.2 and 3.6 log10 IU/mL, respectively. GT1b patients received GS 9451 at a 200 mg once-daily dose, and the median maximal reduction was 3.5 log10 IU/mL. The median half-life of GS 9451 at these doses ranged from 14 to 17 hours, which will allow for once-daily dosing. Treatment-emergent adverse events were generally mild to moderate. Adverse events occurring in at least two patients at any dose were headache (n=7) and dyspepsia (n=2).
Gilead also presented the first Phase I data on a novel NS5A inhibitor for HCV (Study 256-0101), GS 5885, which suggest that this compound also has once-daily dosing potential (Abstract #1883). In preclinical studies, GS 5885 demonstrated low picomolar potency and a favorable safety and pharmacokinetic profile. The clinical safety profile of GS 5885 was assessed in an escalating, single oral dose trial in 54 healthy volunteers (randomized 8:2 to receive GS 5885 versus placebo). The compound was dosed under fasted conditions at 3 mg, 10 mg, 30 mg (under fasted and fed conditions), 60 mg and 100 mg, and was well tolerated, with no serious adverse events and no treatment-emergent grade 3/4 laboratory abnormalities for one week after a single dose. Adverse events were few and generally mild, and included headache, dizziness, myalgia, dysmenorrhea and contact dermatitis from electrocardiogram (ECG) leads. GS 5885 exposure was proportional over the dosing range and produced a mean terminal half-life of 37 to 45 hours, demonstrating potential for once-daily dosing.
Based on the results of the studies presented at The Liver Meeting, Gilead is advancing its HCV pipeline with three new studies slated for initiation before the end of 2010. The first is a Phase IIb clinical trial of GS 9190 and GS 9256 administered with the current standard of care, evaluating the potential to reduce the required duration of HCV therapy (including RBV/Peg-IFN) from 48 to 16 weeks. Similarly, a second Phase IIb trial will assess GS 9190 plus GS 9451 and the current standard of care. Finally, Gilead will be initiating a drug interaction study of GS 5885 in preparation for a Phase IIb study of GS 5885 plus a protease inhibitor and the current standard of care.
GS 9190, GS 9256, GS 9451 and GS 5885 are investigational products and have not yet been determined safe or efficacious in humans.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia.
Gilead's Investigational Hepatitis C Compounds GS 9190 and GS 9256 in Combination with Standard of Care Therapies Achieve Substantial Viral Suppression in Phase II Study
-- Compounds Among the Company's Seven HCV Pipeline Candidates Spanning Six Therapeutic Classes --
BOSTON, Oct 30, 2010 (BUSINESS WIRE) -- Gilead Sciences, Inc today announced data from a Phase IIa study showing that its investigational compounds GS 9190 and GS 9256, used in conjunction with current standard of care therapies, produced substantial suppression of the hepatitis C virus (HCV) within 28 days of treatment. The findings are being presented Monday, November 1, during a latebreaker oral session (#LB-1) at the 61st annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2010) in Boston.
"Patients with chronic hepatitis C urgently need new and better treatment options, particularly combination therapies involving antiviral drugs that employ multiple mechanisms of action to eradicate the virus," said the study's principal investigator, Stefan Zeuzem, MD, JW Goethe University Hospital, Frankfurt, Germany. "The data presented today support the continued clinical evaluation of GS 9190 and GS 9256 in combination with other hepatitis C therapies and provide additional clinical insight into the effect of ribavirin in the absence of interferon."
More than seven million people in industrialized countries are chronically infected with HCV, and as many as three million Americans have the disease. The current standard of care in HCV therapy is the oral antiviral ribavirin (RBV), administered in combination with peg-interferon (Peg-IFN), which is delivered via injection and achieves a sustained therapeutic response in only 40-55 percent of patients with HCV genotype 1, the most common form of HCV in the Americas and Europe.(1)
Gilead's three-arm Phase IIa trial (Study 196-0112) evaluated the safety and efficacy of GS 9190, an oral polymerase inhibitor, in combination with GS 9256, an oral protease inhibitor, when used as: 1) a dual antiviral therapy alone; 2) a three-drug regimen with RBV; or 3) a four-drug regimen with RBV and Peg-IFN. The study found that the all-oral regimen of GS 9190, GS 9256 and RBV produced substantial viral suppression, with a median maximal decline from baseline in HCV RNA of 5.1 log10 IU/mL during 28 days of treatment. Among patients given the four-drug regimen of GS 9190, GS 9256, RBV and Peg-IFN, 100 percent (14/14 patients) achieved Rapid Virologic Response (RVR) (HCV RNA < 25 IU/mL) at day 28, with 93 percent (13/14 patients) achieving undetectable viral levels (HCV RNA < 10 IU/mL). No virologic breakthroughs were observed in this arm.
"Oral combinations of multiple antiviral agents are expected to become the new standard of care for patients with hepatitis C, and our ultimate goal and vision is to develop a potent and well-tolerated fixed-dose combination product that will eliminate the need for peg-interferon," said John McHutchison, MD, Senior Vice President for Liver Disease Therapeutics at Gilead. "These data strongly support the clinical potential of this oral combination HCV therapy, and we're looking forward to advancing the development of GS 9190 and GS 9256."
About Study 196-0112
This Phase IIa, randomized, open-label trial is evaluating GS 9190 and GS 9256 in combination (n=16), and with RBV (n=15) or with RBV/Peg-IFN (n=15). The trial enrolled treatment-naive adults with chronic HCV genotype 1 for a 28-day course of treatment. The primary outcome measures of the trial are the percentage of subjects achieving RVR, defined as HCV RNA < 25 IU/mL at Day 28, as well as the incidence of treatment-related side effects and adverse events.
Patients in the two-drug arm of the study received GS 9190 (40 mg twice daily) and GS 9256 (75 mg twice daily). Patients in the three-drug arm received a regimen of GS 9190, GS 9256 and RBV (1,000-1,200 mg total daily dose, administered twice daily), and patients in the four-drug arm also received Peg-IFN (180 g, injected once per week). In the final analysis, one patient in the four-drug arm was excluded due to a protocol violation. A median maximal decline from baseline HCV RNA of 4.1 log10 IU/mL was observed in patients receiving the two-drug combination of GS 9190 and GS 9256. The addition of RBV and RBV/Peg-IFN enhanced these responses, with median maximal RNA declines of 5.1 log10 IU/mL and 5.7 log10 IU/mL, respectively.
GS 9190 and GS 9256 were generally well tolerated. The majority of adverse events were Grade 1 or 2 in severity and resolved with continued treatment. The most common adverse events observed in each of the three arms were headache, diarrhea and nausea. Some patients taking the three-drug combination also experienced fatigue and insomnia, and some patients taking the four-drug combination experienced influenza-like illness, fatigue, myalgia and cough. There were two serious adverse events including one case of bursitis and a hospitalization for vasovagal collapse (fainting), which was attributed to gastroenteritis and occurred in a patient who continued therapy and achieved RVR. Elevations in bilirubin were observed across all three study arms, the majority of which were Grade 1 or 2 in severity and none of which resulted in study drug discontinuation.
Additional Gilead HCV Pipeline Research
In addition to Study 196-0112, data from seven additional studies will be presented at The Liver Meeting highlighting the clinical profile of the company's other HCV pipeline candidates, including another protease inhibitor, GS 9451, and a novel NS5A inhibitor, GS 5885. Gilead's HCV pipeline now includes seven unique molecules spanning six therapeutic classes with different mechanisms of action. Five of these compounds are currently in clinical trials, and two are slated to enter human clinical studies early next year.
In a Phase I three-day dose-ranging study (Study 169-0103), GS 9451 was found to be highly potent in terms of anti-HCV activity and demonstrated a long plasma half-life with once-daily dosing potential (Abstract #820). GS 9451 was tested among 33 patients with HCV genotype 1a (GT1a) or 1b (GT1b). GT1a patients received GS 9451 at 60 mg, 200 mg and 400 mg once-daily doses, and the median maximal decline from baseline in HCV RNA was 0.88, 3.2 and 3.6 log10 IU/mL, respectively. GT1b patients received GS 9451 at a 200 mg once-daily dose, and the median maximal reduction was 3.5 log10 IU/mL. The median half-life of GS 9451 at these doses ranged from 14 to 17 hours, which will allow for once-daily dosing. Treatment-emergent adverse events were generally mild to moderate. Adverse events occurring in at least two patients at any dose were headache (n=7) and dyspepsia (n=2).
Gilead also presented the first Phase I data on a novel NS5A inhibitor for HCV (Study 256-0101), GS 5885, which suggest that this compound also has once-daily dosing potential (Abstract #1883). In preclinical studies, GS 5885 demonstrated low picomolar potency and a favorable safety and pharmacokinetic profile. The clinical safety profile of GS 5885 was assessed in an escalating, single oral dose trial in 54 healthy volunteers (randomized 8:2 to receive GS 5885 versus placebo). The compound was dosed under fasted conditions at 3 mg, 10 mg, 30 mg (under fasted and fed conditions), 60 mg and 100 mg, and was well tolerated, with no serious adverse events and no treatment-emergent grade 3/4 laboratory abnormalities for one week after a single dose. Adverse events were few and generally mild, and included headache, dizziness, myalgia, dysmenorrhea and contact dermatitis from electrocardiogram (ECG) leads. GS 5885 exposure was proportional over the dosing range and produced a mean terminal half-life of 37 to 45 hours, demonstrating potential for once-daily dosing.
Based on the results of the studies presented at The Liver Meeting, Gilead is advancing its HCV pipeline with three new studies slated for initiation before the end of 2010. The first is a Phase IIb clinical trial of GS 9190 and GS 9256 administered with the current standard of care, evaluating the potential to reduce the required duration of HCV therapy (including RBV/Peg-IFN) from 48 to 16 weeks. Similarly, a second Phase IIb trial will assess GS 9190 plus GS 9451 and the current standard of care. Finally, Gilead will be initiating a drug interaction study of GS 5885 in preparation for a Phase IIb study of GS 5885 plus a protease inhibitor and the current standard of care.
GS 9190, GS 9256, GS 9451 and GS 5885 are investigational products and have not yet been determined safe or efficacious in humans.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia.
Saturday, November 20, 2010
HRSA Awards $1.6 Million to Improve Availability and Expansion of Hepatitis C (HCV) Treatment
A drop in the bucket, but some welcome funding (and increased exposure) for HCV and treatment of HCV in patients with HIV. I'd argue that similar attention and funding be targeted to mono-infection as well given the dire forecast on the financial and health consequences of not treating that population - Chris
ROCKVILLE, Md., Nov. 19, 2010 /PRNewswire via COMTEX/ -- The Health Resources and Services Administration (HRSA) has awarded $1.6 million in grants to support the Hepatitis C Treatment Expansion Initiative. The funds will aid organizations implementing effective, focused interventions designed to increase access to and completion of Hepatitis C (HCV) treatment for HIV-positive patients. Hepatitis C affects about 3.2 million people in the United States, and is responsible for approximately 17,000 deaths each year; about one quarter of HIV-infected persons in the U.S. are also infected with Hepatitis C.
The grants, funded under the Ryan White HIV/AIDS Program, Special Projects of National Significance, were awarded to 15 demonstration sites and one Evaluation and Technical Assistance Center (ETAC). This initiative will evaluate the effectiveness of the interventions to deliver HCV treatment among HIV-positive populations, and share best practice models with Ryan White grantees and other HIV medical providers to improve access and quality of Ryan White services for HIV patients.
"These funds are essential to expanding care and treatment to people living with HIV/AIDS and Hepatitis C" said HRSA Administrator Mary K. Wakefield, R.N., Ph.D. "This is an important opportunity to make measurable progress in treating coexisting conditions and creating a more knowledgeable care community to serve those most in need." The organizations receiving the awards comprise the first of two demonstration site cohorts, each with two-year project periods. In addition, HRSA awarded a separate four-year cooperative agreement to the University of South Florida to serve as the ETAC, which will evaluate and provide technical assistance to the demonstration sites.
Hepatitis C Treatment Expansion Initiative Awards Site City State Total St. Mary Medical Center Foundation Long Beach Calif. $78,954.00 East Bay AIDS Center (EBAC) Oakland Calif. $79,278.00 The Regents of the University of California, San Francisco San Francisco Calif. $80,000.00 Cambridge Health Alliance Cambridge Miss. $80,000.00 Kansas City Free Health Clinic Kansas City Mo. $80,000.00 Washington University St. Louis Mo. $79,935.00 Research Foundation of the State University of New York Albany N.Y.
$80,000.00 Bronx-Lebanon Hospital Center Bronx N.Y.
$80,000.00 Harlem United Community AIDS Center New York N.Y.
$79,860.00 William F. Ryan Community Health Center, Inc. New York N.Y.
$80,000.00 Clarion University of Pennsylvania Clarion Pa. $80,000.00 Bexar County Hospital District (dba University Health System) San Antonio Texas $80,000.00 Carilion Medical Center Roanoke Va. $79,390.00 Inova Health Care Services Springfield Va. $80,000.00 AIDS Resource Center of Wisconsin Milwaukee Wis.
$80,000.00 Total $1,197,417.00 Evaluation and Technical Assistant Center University of South Florida Tampa Fla.
$374,863.00 Grand Total $1,572,280.00 The Health Resources and Services Administration is part of the U.S. Department of Health and Human Services. HRSA is the primary Federal agency responsible for improving access to health care services for people who are uninsured, isolated, or medically vulnerable. For more information about HRSA and its programs, visit www.hrsa.gov.
SOURCE Health Resources and Services Administration (HRSA) www.prnewswire.com Copyright (C) 2010 PR Newswire. All rights reserved -0- KEYWORD: Maryland INDUSTRY KEYWORD: HEA
ROCKVILLE, Md., Nov. 19, 2010 /PRNewswire via COMTEX/ -- The Health Resources and Services Administration (HRSA) has awarded $1.6 million in grants to support the Hepatitis C Treatment Expansion Initiative. The funds will aid organizations implementing effective, focused interventions designed to increase access to and completion of Hepatitis C (HCV) treatment for HIV-positive patients. Hepatitis C affects about 3.2 million people in the United States, and is responsible for approximately 17,000 deaths each year; about one quarter of HIV-infected persons in the U.S. are also infected with Hepatitis C.
The grants, funded under the Ryan White HIV/AIDS Program, Special Projects of National Significance, were awarded to 15 demonstration sites and one Evaluation and Technical Assistance Center (ETAC). This initiative will evaluate the effectiveness of the interventions to deliver HCV treatment among HIV-positive populations, and share best practice models with Ryan White grantees and other HIV medical providers to improve access and quality of Ryan White services for HIV patients.
"These funds are essential to expanding care and treatment to people living with HIV/AIDS and Hepatitis C" said HRSA Administrator Mary K. Wakefield, R.N., Ph.D. "This is an important opportunity to make measurable progress in treating coexisting conditions and creating a more knowledgeable care community to serve those most in need." The organizations receiving the awards comprise the first of two demonstration site cohorts, each with two-year project periods. In addition, HRSA awarded a separate four-year cooperative agreement to the University of South Florida to serve as the ETAC, which will evaluate and provide technical assistance to the demonstration sites.
Hepatitis C Treatment Expansion Initiative Awards Site City State Total St. Mary Medical Center Foundation Long Beach Calif. $78,954.00 East Bay AIDS Center (EBAC) Oakland Calif. $79,278.00 The Regents of the University of California, San Francisco San Francisco Calif. $80,000.00 Cambridge Health Alliance Cambridge Miss. $80,000.00 Kansas City Free Health Clinic Kansas City Mo. $80,000.00 Washington University St. Louis Mo. $79,935.00 Research Foundation of the State University of New York Albany N.Y.
$80,000.00 Bronx-Lebanon Hospital Center Bronx N.Y.
$80,000.00 Harlem United Community AIDS Center New York N.Y.
$79,860.00 William F. Ryan Community Health Center, Inc. New York N.Y.
$80,000.00 Clarion University of Pennsylvania Clarion Pa. $80,000.00 Bexar County Hospital District (dba University Health System) San Antonio Texas $80,000.00 Carilion Medical Center Roanoke Va. $79,390.00 Inova Health Care Services Springfield Va. $80,000.00 AIDS Resource Center of Wisconsin Milwaukee Wis.
$80,000.00 Total $1,197,417.00 Evaluation and Technical Assistant Center University of South Florida Tampa Fla.
$374,863.00 Grand Total $1,572,280.00 The Health Resources and Services Administration is part of the U.S. Department of Health and Human Services. HRSA is the primary Federal agency responsible for improving access to health care services for people who are uninsured, isolated, or medically vulnerable. For more information about HRSA and its programs, visit www.hrsa.gov.
SOURCE Health Resources and Services Administration (HRSA) www.prnewswire.com Copyright (C) 2010 PR Newswire. All rights reserved -0- KEYWORD: Maryland INDUSTRY KEYWORD: HEA
Friday, November 19, 2010
NEWSMAX.com lists the Top 10 Hepatitis Treatment Centers...
I'm sure Newsmax, being the fair balanced news source it is *cough* has very good intentions with this top 10 list of centers that treat Hepatitis C. However, they don't reveal to us regular folks on what the criteria is to get in the Top 10. Outcomes? Patient satisfaction? quality of clinical research? High-dollar Republican campaign contributions? Anyway, it is what it is - Chris
Hepatitis C: Top 10 Treatment Centers
Tuesday, November 16, 2010 12:00 PM
Hepatitis C is a viral liver disease that may include pain in the liver or abdominal area, and jaundice like symptoms where both the white of the eyes and the skin turn yellow. Hepatitis may cause the urine to appear dark in color while stools appear pale. The disease is also marked by fatigue, confusion, and irritability.
Other symptoms during the onset of the infection include a loss of appetite, diarrhea, nausea, and vomiting. Some chronic Hepatitis C cases have symptoms of sleep disturbance, itchy skin, vomiting blood, hallucination, edema or fluid retention, and swelling of the abdomen, legs, and face.
The top ten treatment centers for Hepatitis C are:
1. Gastroenterology Associates of East Bay Medical Group, Berkeley, California
2. Atlanta Gastroenterology Associates, Atlanta, Georgia
3. Idaho Gastroenterology Associates, Meridian, Idaho
4. Johns Hopkins University, Baltimore, Maryland
5. Carolinas Center for Liver Diseases, Charlotte, North Carolina
6. Baylor University Medical Center, Dallas, Texas
7. Wisconsin Center for Advanced Research, Milwaukee, Wisconsin
8. University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
9. Washington Hospital Center, Washington, District of Columbia
10. University of Miami Center for Liver Diseases, Miami, Florida
Hepatitis C: Top 10 Treatment Centers
Tuesday, November 16, 2010 12:00 PM
Hepatitis C is a viral liver disease that may include pain in the liver or abdominal area, and jaundice like symptoms where both the white of the eyes and the skin turn yellow. Hepatitis may cause the urine to appear dark in color while stools appear pale. The disease is also marked by fatigue, confusion, and irritability.
Other symptoms during the onset of the infection include a loss of appetite, diarrhea, nausea, and vomiting. Some chronic Hepatitis C cases have symptoms of sleep disturbance, itchy skin, vomiting blood, hallucination, edema or fluid retention, and swelling of the abdomen, legs, and face.
The top ten treatment centers for Hepatitis C are:
1. Gastroenterology Associates of East Bay Medical Group, Berkeley, California
2. Atlanta Gastroenterology Associates, Atlanta, Georgia
3. Idaho Gastroenterology Associates, Meridian, Idaho
4. Johns Hopkins University, Baltimore, Maryland
5. Carolinas Center for Liver Diseases, Charlotte, North Carolina
6. Baylor University Medical Center, Dallas, Texas
7. Wisconsin Center for Advanced Research, Milwaukee, Wisconsin
8. University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
9. Washington Hospital Center, Washington, District of Columbia
10. University of Miami Center for Liver Diseases, Miami, Florida
Thursday, November 18, 2010
Medivir/Tibotec's TMC435 looking good in partial and non-responders....
This should get interesting in terms of revenue streams - Medivir is developing TMC435 with Tibotec who will market the drug in the US. Tibotec has marketing rights for Telaprevir everywhere except North America and the Far East. Telaprevir will be out first, depending on how things go with the European regulatory folks. How Tibotec prioritizes TMC435 development with Telaprevir marketing abroad is unclear. Looks like a darn good drug though. Good numbers and QD dosing.
By Frances Schwartzkopff - Nov 18, 2010
Medivir AB, the drugmaker competing to develop a new hepatitis C medicine, rose the most in four months in Stockholm trading after its drug reduced the virus to undetectable levels in patients who failed earlier treatment.
After 24 weeks, 86 percent of patients who had only partially responded to earlier treatment had undetectable virus levels after taking TMC435 alongside standard care, the Huddinge, Sweden-based company said in a study published today. That compared with undetectable levels in 19 percent of patients receiving a placebo. Shares rose as much as 9.2 percent.
Medivir is developing TMC435 with Tibotec Pharmaceuticals. The drugmaker, a unit of New Brunswick, New Jersey-based Johnson & Johnson, also is working simultaneously with Vertex Pharmaceuticals Inc. on a new hepatitis C drug.
Vertex, based in Cambridge, Massachusetts, plans to seek U.S. approval for its medicine, Telaprevir, by the end of the year.
Medivir, which still needs to conduct the last trial needed to seek regulatory approval, said 78 percent of patients who didn’t respond at all to initial treatment had undetectable virus levels after taking TMC435, almost twice as many as those who received a placebo.
The medication also led to undetectable virus levels in 94 percent of patients who had relapsed after receiving earlier care. That compared with 83 percent of patients taking a placebo. 462 patients participated in the 48-week study, with results taken half way through.
Medivir rose 8.5 kronor, or 6.8 percent, to 133.5 kronor at 12:54 p.m. local time. The advance gave the drugmaker a market value of 3.5 billion kronor ($511 million), its highest since December 2000.
By Frances Schwartzkopff - Nov 18, 2010
Medivir AB, the drugmaker competing to develop a new hepatitis C medicine, rose the most in four months in Stockholm trading after its drug reduced the virus to undetectable levels in patients who failed earlier treatment.
After 24 weeks, 86 percent of patients who had only partially responded to earlier treatment had undetectable virus levels after taking TMC435 alongside standard care, the Huddinge, Sweden-based company said in a study published today. That compared with undetectable levels in 19 percent of patients receiving a placebo. Shares rose as much as 9.2 percent.
Medivir is developing TMC435 with Tibotec Pharmaceuticals. The drugmaker, a unit of New Brunswick, New Jersey-based Johnson & Johnson, also is working simultaneously with Vertex Pharmaceuticals Inc. on a new hepatitis C drug.
Vertex, based in Cambridge, Massachusetts, plans to seek U.S. approval for its medicine, Telaprevir, by the end of the year.
Medivir, which still needs to conduct the last trial needed to seek regulatory approval, said 78 percent of patients who didn’t respond at all to initial treatment had undetectable virus levels after taking TMC435, almost twice as many as those who received a placebo.
The medication also led to undetectable virus levels in 94 percent of patients who had relapsed after receiving earlier care. That compared with 83 percent of patients taking a placebo. 462 patients participated in the 48-week study, with results taken half way through.
Medivir rose 8.5 kronor, or 6.8 percent, to 133.5 kronor at 12:54 p.m. local time. The advance gave the drugmaker a market value of 3.5 billion kronor ($511 million), its highest since December 2000.
Wednesday, November 17, 2010
Unmet needs spur innovative drug development for Hepatitis C...
Article I authored for TrendSlate blog.
Large, unmet needs in medicine have always spurred innovation in novel drug development. A textbook case of this can be found in the effort to fight Hepatitis C (HCV) infection. Hepatitis C is a blood borne virus that primarily affects the liver. The virus triggers an immune response – one that the virus almost always successfully evades– causing liver inflammation and scarring. Slowly, over a period of 20-30 years in most cases, the scarring can progress to decompensated cirrhosis, liver cancer and eventually liver failure. Lack of general knowledge regarding the disease in both the patient and healthcare provider population has created an environment of chronic underscreening, underdiagnosis and lack of proper treatment.
By the most conservative of estimates, researchers have put the worldwide number of HCV infected at 180 million, with 3 to 5 million here in the United States. With large portion of the infections occurring before the early 90’s when an effective technology came out to screen the blood donor pool, most of the burden of the disease sits squarely on the shoulders of those born between 1946 and 1964 – the baby boomer generation. Given that the progression of disease from infection to liver damage is roughly 20 years, there has been a correlating recent uptick in the worldwide incidence of liver disease. Without an effective therapy, experts expect a four fold increase in the incidence of Hepatitis C-related liver disease in the next 20 years. Inextricably linked are healthcare costs… a highly regarded 2009 forecast from the Milliman Consulting Group pegs an increase in healthcare costs from the current $30 billion to over $85 billion in 2027. Most of that burden is forecasted to fall in the lap of already-cash strapped government payors. That is one financial tidal wave to be avoided.
The current treatment for Hepatitis C is arduous for both patient and provider, costly and comes with a largely insufficient cure rate, especially genotype 1, the most common genotype found in the United States. With a 50% cure rate at best (called ‘SVR’ or ‘Sustained Viral Response’), the current treatment of pegylated interferon and nucleoside analog ribavirin is also fraught with side events and tolerability issues that make it not unlike a 48 week endurance contest. Pegylated interferon works by stimulating the host immune response and ribavirin is thought to work by preventing relapse, although it’s exact mechanism of action is unknown. Using the two together means 48 weeks of flu-like symptoms, depression and fatigue. With 50% of patients not responding and/or tolerating this regimen, there is certainly a lot of room for improvement. This fact, coupled with a refocused FDA prioritizing reviews with an eye out for compounds that meet unmet disease states, make HCV an attractive target for intrepid drug developers.
From the scrappiest of the little Biopharma startups to the biggest of behemoth Big Pharma companies, there is plenty of innovation going in developing drugs to effectively treat HCV. As I’m typing this, there are currently over 120 compounds in all stages of development with new ones being added as others undoubtedly falter. Most of these new compounds fall under the umbrella of “STAT-C Drugs” or “Specifically Targeted Antiviral Therapy for Hepatitis C”, Unlike the non-specific method of action of pegylated interferon and ribavirin, STAT-C drugs are a new class of compounds that customized to target specific areas integral to the life cycle of Hepatitis C virus. The goal is to terminate that life cycle, thereby preventing viral replication.
Nearest to market are Vertex Pharmaceuticals and Merck with HCV protease inhibitors Telaprevir and Boceprevir respectively, due to hit the market at about the same time in 2011. Some experts even predict a dual FDA review which will surely test the mettle of both companies. It is fitting, however, that Vertex is amongst the leaders in STAT-C development. They fired the first shot in the equivalent of a drug development revolution when Vertex scientists first published the structure of the HCV protease in 1996 and then used computer-generated modeling to design molecules to bind to the protease. Unlike the HIV protease, HCV didn’t present a nice, big pocket to fit a molecule in. The binding site of the HCV protease was described as more of a “dent in a dinner plate”, making the design more difficult. That program created the Telaprevir molecule. Vertex did it again in 1998, identifying the 3D structure of the NS3 HCV Helicase. This, however, has been a less successful target than the protease. No doubt that both discoveries lead to a industry-wide gold rush in HCV drug development. The forecasted revenue for these two novel drugs? Between 2-3 billion by 2014 for Vertex’s Telaprevir alone, according to some market oracles.
In terms of competition, it looks as if both Vertex and Merck look to have the STAT-C market to themselves for two or three years. Both companies have additional STAT-C compounds in in the pipeline. Looming closely behind are companies like Roche, Bristol Meyers Squibb, Gilead, Boehringer Ingelheim and Tibotec with their own compounds and no shortage of capital to get them to market. Yet despite the leaps in drug development innovation for HCV, a big, yet unanswered question remains. All the trials with both Telaprevir and Boceprevir were done in combination with the current standard of care, pegylated interferon and ribavirin. The addition of either compound provided an average increase in SVR of around 20% and cut the duration of therapy by 50% compared to pegylated interferon and ribavirin alone. Both compounds added additional leverage in boosting the SVRs of patients that had been previously treated but were not cured as well as making significant inroads in populations that have significant genetic barriers to treatment success such as Hispanics and African Americans. A 20% increase in SVR in half the time is remarkable achievement. The fact remains however, that even 12-16 weeks of treatment may be rough to get through given the side effect baggage of pegylated interferon and ribavirin combined with the additional side effects of the new compounds. If a combination of better-tolerated STAT-C drugs can be robust enough to prevent viral resistance and breakthrough without the non-virus specific immune modulating effects of peyglated interferon and ribavirin, even more patients could be treated.
Don’t think drug developers haven’t dreamed of ditching pegylated interferon and ribavirin. Many of the aforementioned companies are doing trials using their STAT-C regimens in combination both with and without pegylated interferon and ribavirin to explore the possibilities. Is it reasonable to think a virus that mutates so rapidly as to create every single possible mutation of itself every day be outwitted by drugs that target multiple points of the virus life cycle? The jury is still out. Vertex recently discontinued an arm in their trial pairing Telaprevir with a low dose of their non-nucleoside polymerase inhibitor VX-222 without pegylated interferon and ribavirin because some patients experienced viral breakthrough. In the higher dose arms, they paired Telaprevir plus VX-222 as well as pegylated interferon and ribavirin and at the time of the press release, those patients remained undetectable. Other trials with different combinations of drugs are currently progressing, so that particular question remains without a definitive answer.
Whatever the ultimate outcome for the STAT-C drugs, it’s clear that a significant milestone has been achieved in terms of drug development. Science and innovation are addressing a clear unmet need. We have an upcoming armory of novel compounds aimed at turning the $85 billion dollar tidal wave into a mere ripple by cutting the down the duration of therapy, increasing SVR and ultimately saving lives. Drugs will continue to improve as developers work to reduce adverse events, increase efficacy and make dosing more convenient. We’ll also witness dramatic shifts in the marketplace due to cost – how will the evolving managed care environment embrace the STAT-C drugs? What effects will STAT-C drugs have on utilization and provider reimbursement? How will patient assistance programs be designed? What role will support groups, community advocates and politics play in educating the masses on the disease and it’s treatment? What are the barriers to access to care? What about drug interactions and resistance profiles? What does HCV viral resistance mean? It is indeed a very exciting time for drug development, but definitely not for the faint of heart
Large, unmet needs in medicine have always spurred innovation in novel drug development. A textbook case of this can be found in the effort to fight Hepatitis C (HCV) infection. Hepatitis C is a blood borne virus that primarily affects the liver. The virus triggers an immune response – one that the virus almost always successfully evades– causing liver inflammation and scarring. Slowly, over a period of 20-30 years in most cases, the scarring can progress to decompensated cirrhosis, liver cancer and eventually liver failure. Lack of general knowledge regarding the disease in both the patient and healthcare provider population has created an environment of chronic underscreening, underdiagnosis and lack of proper treatment.
By the most conservative of estimates, researchers have put the worldwide number of HCV infected at 180 million, with 3 to 5 million here in the United States. With large portion of the infections occurring before the early 90’s when an effective technology came out to screen the blood donor pool, most of the burden of the disease sits squarely on the shoulders of those born between 1946 and 1964 – the baby boomer generation. Given that the progression of disease from infection to liver damage is roughly 20 years, there has been a correlating recent uptick in the worldwide incidence of liver disease. Without an effective therapy, experts expect a four fold increase in the incidence of Hepatitis C-related liver disease in the next 20 years. Inextricably linked are healthcare costs… a highly regarded 2009 forecast from the Milliman Consulting Group pegs an increase in healthcare costs from the current $30 billion to over $85 billion in 2027. Most of that burden is forecasted to fall in the lap of already-cash strapped government payors. That is one financial tidal wave to be avoided.
The current treatment for Hepatitis C is arduous for both patient and provider, costly and comes with a largely insufficient cure rate, especially genotype 1, the most common genotype found in the United States. With a 50% cure rate at best (called ‘SVR’ or ‘Sustained Viral Response’), the current treatment of pegylated interferon and nucleoside analog ribavirin is also fraught with side events and tolerability issues that make it not unlike a 48 week endurance contest. Pegylated interferon works by stimulating the host immune response and ribavirin is thought to work by preventing relapse, although it’s exact mechanism of action is unknown. Using the two together means 48 weeks of flu-like symptoms, depression and fatigue. With 50% of patients not responding and/or tolerating this regimen, there is certainly a lot of room for improvement. This fact, coupled with a refocused FDA prioritizing reviews with an eye out for compounds that meet unmet disease states, make HCV an attractive target for intrepid drug developers.
From the scrappiest of the little Biopharma startups to the biggest of behemoth Big Pharma companies, there is plenty of innovation going in developing drugs to effectively treat HCV. As I’m typing this, there are currently over 120 compounds in all stages of development with new ones being added as others undoubtedly falter. Most of these new compounds fall under the umbrella of “STAT-C Drugs” or “Specifically Targeted Antiviral Therapy for Hepatitis C”, Unlike the non-specific method of action of pegylated interferon and ribavirin, STAT-C drugs are a new class of compounds that customized to target specific areas integral to the life cycle of Hepatitis C virus. The goal is to terminate that life cycle, thereby preventing viral replication.
Nearest to market are Vertex Pharmaceuticals and Merck with HCV protease inhibitors Telaprevir and Boceprevir respectively, due to hit the market at about the same time in 2011. Some experts even predict a dual FDA review which will surely test the mettle of both companies. It is fitting, however, that Vertex is amongst the leaders in STAT-C development. They fired the first shot in the equivalent of a drug development revolution when Vertex scientists first published the structure of the HCV protease in 1996 and then used computer-generated modeling to design molecules to bind to the protease. Unlike the HIV protease, HCV didn’t present a nice, big pocket to fit a molecule in. The binding site of the HCV protease was described as more of a “dent in a dinner plate”, making the design more difficult. That program created the Telaprevir molecule. Vertex did it again in 1998, identifying the 3D structure of the NS3 HCV Helicase. This, however, has been a less successful target than the protease. No doubt that both discoveries lead to a industry-wide gold rush in HCV drug development. The forecasted revenue for these two novel drugs? Between 2-3 billion by 2014 for Vertex’s Telaprevir alone, according to some market oracles.
In terms of competition, it looks as if both Vertex and Merck look to have the STAT-C market to themselves for two or three years. Both companies have additional STAT-C compounds in in the pipeline. Looming closely behind are companies like Roche, Bristol Meyers Squibb, Gilead, Boehringer Ingelheim and Tibotec with their own compounds and no shortage of capital to get them to market. Yet despite the leaps in drug development innovation for HCV, a big, yet unanswered question remains. All the trials with both Telaprevir and Boceprevir were done in combination with the current standard of care, pegylated interferon and ribavirin. The addition of either compound provided an average increase in SVR of around 20% and cut the duration of therapy by 50% compared to pegylated interferon and ribavirin alone. Both compounds added additional leverage in boosting the SVRs of patients that had been previously treated but were not cured as well as making significant inroads in populations that have significant genetic barriers to treatment success such as Hispanics and African Americans. A 20% increase in SVR in half the time is remarkable achievement. The fact remains however, that even 12-16 weeks of treatment may be rough to get through given the side effect baggage of pegylated interferon and ribavirin combined with the additional side effects of the new compounds. If a combination of better-tolerated STAT-C drugs can be robust enough to prevent viral resistance and breakthrough without the non-virus specific immune modulating effects of peyglated interferon and ribavirin, even more patients could be treated.
Don’t think drug developers haven’t dreamed of ditching pegylated interferon and ribavirin. Many of the aforementioned companies are doing trials using their STAT-C regimens in combination both with and without pegylated interferon and ribavirin to explore the possibilities. Is it reasonable to think a virus that mutates so rapidly as to create every single possible mutation of itself every day be outwitted by drugs that target multiple points of the virus life cycle? The jury is still out. Vertex recently discontinued an arm in their trial pairing Telaprevir with a low dose of their non-nucleoside polymerase inhibitor VX-222 without pegylated interferon and ribavirin because some patients experienced viral breakthrough. In the higher dose arms, they paired Telaprevir plus VX-222 as well as pegylated interferon and ribavirin and at the time of the press release, those patients remained undetectable. Other trials with different combinations of drugs are currently progressing, so that particular question remains without a definitive answer.
Whatever the ultimate outcome for the STAT-C drugs, it’s clear that a significant milestone has been achieved in terms of drug development. Science and innovation are addressing a clear unmet need. We have an upcoming armory of novel compounds aimed at turning the $85 billion dollar tidal wave into a mere ripple by cutting the down the duration of therapy, increasing SVR and ultimately saving lives. Drugs will continue to improve as developers work to reduce adverse events, increase efficacy and make dosing more convenient. We’ll also witness dramatic shifts in the marketplace due to cost – how will the evolving managed care environment embrace the STAT-C drugs? What effects will STAT-C drugs have on utilization and provider reimbursement? How will patient assistance programs be designed? What role will support groups, community advocates and politics play in educating the masses on the disease and it’s treatment? What are the barriers to access to care? What about drug interactions and resistance profiles? What does HCV viral resistance mean? It is indeed a very exciting time for drug development, but definitely not for the faint of heart
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