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.
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