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).
Tuesday, November 30, 2010
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
Tuesday, November 16, 2010
Zobair M. Younossi, MD discusses "A New Era of Hepatitis C Therapy"
Zobair M. Younossi, MD, the Executive Director of the Center for Liver Diseases and Vice President of Research at the Inova Health System in Falls Church, Virginia discusses the STAT-C drugs and other novel therapies for Hepatitis C from AASLD 2010. Features a video and transcript. Watch and read here.
Wednesday, November 10, 2010
Vertex adds ribavirin in additional treatment arm in ongoing Phase II VX-222 & Telaprevir combo trial...
-New treatment arm to evaluate all oral, triple combination regimen of telaprevir, VX-222, and ribavirin-
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced plans to enroll an additional treatment arm as part of its ongoing Phase 2 clinical trial evaluating 12-week regimens of Vertex's lead investigational hepatitis C virus (HCV) protease inhibitor, telaprevir, in combination with its lead investigational HCV polymerase inhibitor, VX-222. The planned treatment arm is supported by emerging data from multiple ongoing clinical trials of direct-acting antiviral (DAA) therapies, including the trial of telaprevir/VX-222-based combination therapy, which suggest that adding ribavirin to a DAA treatment regimen may increase antiviral activity. In the additional arm, Vertex plans to evaluate a 12-week combination of three oral therapies — VX-222, telaprevir and ribavirin — dosed twice a day within a response-guided regimen.
"We are encouraged by the high viral cure rates and shorter treatment durations reported in Phase 3 studies of telaprevir-based combination therapy, and we remain focused on continuing to develop new potential treatments for hepatitis C," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "Evaluating a 12-week combination of telaprevir, VX-222 and ribavirin will provide us with important information about the potential for this all-oral regimen that could be taken twice a day."
About the Ongoing Phase 2 Trial of Telaprevir and VX-222
Beginning in August 2010, patients enrolled in the randomized, parallel-group, dose-ranging Phase 2 trial started receiving treatment. The primary endpoint of this trial is to assess safety and tolerability of 12-week telaprevir/VX-222-based combination therapy in people with genotype 1 chronic hepatitis C. A secondary endpoint of this study is to assess on-treatment antiviral activity and the proportion of patients in each study arm who achieve a sustained viral response (SVR; defined as undetectable HCV RNA 24 weeks after the end of treatment). If patients meet response-guided criteria during treatment (undetectable HCV RNA at week 2 and week 8 of treatment), they may be eligible to stop all therapy at 12 weeks.
The study includes treatment arms that are evaluating 12-week, response-guided regimens of two- and four-drug telaprevir/VX-222 combination therapy, given twice daily, with and without Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin). Trial sites for the two- and four-drug ongoing arms completed enrollment in October 2010. The additional three-drug treatment arm of telaprevir, VX-222 and ribavirin announced today is expected to begin patient enrollment in the first quarter of 2011, pending completion of institutional review board (IRB) approvals and consultation with regulatory agencies. Based on further results from the ongoing treatment arms, Vertex may add an additional arm in this study.
Additional Clinical Trial of VX-222 Combination Therapy
Vertex is also conducting a Phase 2 clinical trial evaluating the safety, tolerability and antiviral activity of VX-222 in combination with pegylated-interferon and ribavirin, which began in August 2010. Enrollment is ongoing and Vertex expects to enroll a total of 50 patients. Patients in this trial will receive one of two doses of VX-222 (400 mg or 750 mg twice daily) in combination with pegylated-interferon alfa-2a and ribavirin for 12 weeks, followed by pegylated-interferon alfa-2a and ribavirin alone for 36 weeks.
About Telaprevir and VX-222
Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being developed by Vertex Pharmaceuticals in collaboration with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. Phase 3 studies of telaprevir in combination with pegylated interferon alfa-2a and ribavirin are complete and Vertex is on track to complete its rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration by the end of 2010.
VX-222 is an investigational, oral, non-nucleoside inhibitor of HCV NS5B polymerase. Vertex added VX-222 to its development pipeline as part of the acquisition of ViroChem Pharma Inc. in March 2009. Vertex retains worldwide commercial rights to VX-222.
About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the liver and blood of people with the disease.2 According to a 2010 report from the Institute of Medicine, up to 3.9 million people in the United States have chronic hepatitis C and 75% of those infected are unaware of their infection.3 Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved treatment regimen, do not achieve SVR, 4,5,6 or viral cure.1
Hepatitis C is spread through direct contact with the blood of infected people.2 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.2 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.2 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8,9,10,11 In the United States, hepatitis C is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.8 The majority of people with hepatitis C were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.11 By 2029, total annual medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.11
Additional resources for media, including a hepatitis C backgrounder and glossary of common terms, are available at: http://investors.vrtx.com/press.cfm
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced plans to enroll an additional treatment arm as part of its ongoing Phase 2 clinical trial evaluating 12-week regimens of Vertex's lead investigational hepatitis C virus (HCV) protease inhibitor, telaprevir, in combination with its lead investigational HCV polymerase inhibitor, VX-222. The planned treatment arm is supported by emerging data from multiple ongoing clinical trials of direct-acting antiviral (DAA) therapies, including the trial of telaprevir/VX-222-based combination therapy, which suggest that adding ribavirin to a DAA treatment regimen may increase antiviral activity. In the additional arm, Vertex plans to evaluate a 12-week combination of three oral therapies — VX-222, telaprevir and ribavirin — dosed twice a day within a response-guided regimen.
"We are encouraged by the high viral cure rates and shorter treatment durations reported in Phase 3 studies of telaprevir-based combination therapy, and we remain focused on continuing to develop new potential treatments for hepatitis C," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "Evaluating a 12-week combination of telaprevir, VX-222 and ribavirin will provide us with important information about the potential for this all-oral regimen that could be taken twice a day."
About the Ongoing Phase 2 Trial of Telaprevir and VX-222
Beginning in August 2010, patients enrolled in the randomized, parallel-group, dose-ranging Phase 2 trial started receiving treatment. The primary endpoint of this trial is to assess safety and tolerability of 12-week telaprevir/VX-222-based combination therapy in people with genotype 1 chronic hepatitis C. A secondary endpoint of this study is to assess on-treatment antiviral activity and the proportion of patients in each study arm who achieve a sustained viral response (SVR; defined as undetectable HCV RNA 24 weeks after the end of treatment). If patients meet response-guided criteria during treatment (undetectable HCV RNA at week 2 and week 8 of treatment), they may be eligible to stop all therapy at 12 weeks.
The study includes treatment arms that are evaluating 12-week, response-guided regimens of two- and four-drug telaprevir/VX-222 combination therapy, given twice daily, with and without Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin). Trial sites for the two- and four-drug ongoing arms completed enrollment in October 2010. The additional three-drug treatment arm of telaprevir, VX-222 and ribavirin announced today is expected to begin patient enrollment in the first quarter of 2011, pending completion of institutional review board (IRB) approvals and consultation with regulatory agencies. Based on further results from the ongoing treatment arms, Vertex may add an additional arm in this study.
Additional Clinical Trial of VX-222 Combination Therapy
Vertex is also conducting a Phase 2 clinical trial evaluating the safety, tolerability and antiviral activity of VX-222 in combination with pegylated-interferon and ribavirin, which began in August 2010. Enrollment is ongoing and Vertex expects to enroll a total of 50 patients. Patients in this trial will receive one of two doses of VX-222 (400 mg or 750 mg twice daily) in combination with pegylated-interferon alfa-2a and ribavirin for 12 weeks, followed by pegylated-interferon alfa-2a and ribavirin alone for 36 weeks.
About Telaprevir and VX-222
Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being developed by Vertex Pharmaceuticals in collaboration with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. Phase 3 studies of telaprevir in combination with pegylated interferon alfa-2a and ribavirin are complete and Vertex is on track to complete its rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration by the end of 2010.
VX-222 is an investigational, oral, non-nucleoside inhibitor of HCV NS5B polymerase. Vertex added VX-222 to its development pipeline as part of the acquisition of ViroChem Pharma Inc. in March 2009. Vertex retains worldwide commercial rights to VX-222.
About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the liver and blood of people with the disease.2 According to a 2010 report from the Institute of Medicine, up to 3.9 million people in the United States have chronic hepatitis C and 75% of those infected are unaware of their infection.3 Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved treatment regimen, do not achieve SVR, 4,5,6 or viral cure.1
Hepatitis C is spread through direct contact with the blood of infected people.2 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.2 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.2 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8,9,10,11 In the United States, hepatitis C is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.8 The majority of people with hepatitis C were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.11 By 2029, total annual medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.11
Additional resources for media, including a hepatitis C backgrounder and glossary of common terms, are available at: http://investors.vrtx.com/press.cfm
Monday, November 8, 2010
New Journal article: Forthcoming challenges in the management of STAT-C therapy
New article "Forthcoming challenges in the management of STAT-C therapy" published online in Digestive and Liver Diseases(full article available in PDF format as well). This is the first article I've seen addressing the importance pharmacokinetics in STAT-C therapy and applies some of what we've learned from HIV antiretroviral therapy. Definitely worth a read - Cmin/IC50 ratios DO matter!!
Forthcoming challenges in the management of STAT-C therapy
Raffaele Bruno, Serena Cima, Laura Maiocchi, Paolo Sacchi
Received 22 July 2010; accepted 9 September 2010. published online 27 October 2010.
Corrected Proof
Abstract
Agents that specifically target the replication cycle of the virus [specifically targeted antiviral therapies for hepatitis C (STAT-Cs)] by directly inhibiting the NS3/4A serine protease, the NS5B polymerase and NS5A are currently in clinical development. The need to achieve serum drug concentrations able to suppress viral replication is a key factor for a successful antiviral therapy and the prevention of resistance. Thus pharmacokinetics parameters became important issues for drugs used in the therapy of hepatitis C. The ratio of Cmin/IC50 (inhibitory quotient or IQ) can provide a surrogate measure of a drug's ability to suppress HCV replication, by taking into account the relationship between plasma drug levels and viral susceptibility to the drug. Ritonavir boosting may be a useful strategy to improve pharmacokinetic parameters. Characterising resistance to STAT-Cs in clinical trials is essential for the management of a drug regimen to reduce the development of resistance and thereby maximise SVR rate. The lesson of HIV therapy, provide a compelling case for the exploration of combinations of direct-acting antiviral agents.
Forthcoming challenges in the management of STAT-C therapy
Raffaele Bruno, Serena Cima, Laura Maiocchi, Paolo Sacchi
Received 22 July 2010; accepted 9 September 2010. published online 27 October 2010.
Corrected Proof
Abstract
Agents that specifically target the replication cycle of the virus [specifically targeted antiviral therapies for hepatitis C (STAT-Cs)] by directly inhibiting the NS3/4A serine protease, the NS5B polymerase and NS5A are currently in clinical development. The need to achieve serum drug concentrations able to suppress viral replication is a key factor for a successful antiviral therapy and the prevention of resistance. Thus pharmacokinetics parameters became important issues for drugs used in the therapy of hepatitis C. The ratio of Cmin/IC50 (inhibitory quotient or IQ) can provide a surrogate measure of a drug's ability to suppress HCV replication, by taking into account the relationship between plasma drug levels and viral susceptibility to the drug. Ritonavir boosting may be a useful strategy to improve pharmacokinetic parameters. Characterising resistance to STAT-Cs in clinical trials is essential for the management of a drug regimen to reduce the development of resistance and thereby maximise SVR rate. The lesson of HIV therapy, provide a compelling case for the exploration of combinations of direct-acting antiviral agents.
Saturday, November 6, 2010
GlobeImmune's GI-5005 HCV Therapeutic Vaccine increases SVR by 12% in previous treatment failures
By Liz Jones Hollis (http://www.fiercebiotech.com/node/93538/print)
Created Nov 4 2010 - 6:56am
Phase 2b Study Demonstrates GlobeImmune's GI-5005 HCV Therapeutic Vaccine Increases Sustained Virologic Response by 12 Percent in Patients Who Previously Failed Therapy with Standard of Care.
Additional data suggest that cellular immunity may be a fundamental deficit in hardest-to-treat IL28B T/T genotype patients and is corrected by GI-5005
Data to be presented at annual meeting of the American Association for the Study of the Liver Diseases
LOUISVILLE, Colo., October 30, 2010 - GlobeImmune Inc. today announced additional data from the GI-5005-02 Phase 2b study demonstrating that GI-5005, the Company's investigational Tarmogen® product, improved sustained virologic response (SVR) by 12% in patients with genotype 1 chronic hepatitis C virus (HCV) infection who had failed prior treatment with standard of care (SOC, pegylated-interferon alpha 2a plus ribavirin). This study suggests that GI-5005 may have the potential to be the first successful therapeutic vaccine for patients chronically infected with HCV.
Paul J. Pockros, M.D., of Scripps Clinic will deliver the oral presentation of the results in a late-breaker session at 6 p.m. EDT Monday November 1, 2010 at the 61st Annual Meeting of the American Association for the Study of the Liver Diseases (AASLD) in Boston.
On an intent-to-treat basis (subjects who received at least one dose of combination therapy), prior non-responders receiving GI-5005 plus SOC as a triple therapy had an SVR rate of 17%, compared to an SVR rate of only 5% in patients receiving SOC alone. Prior non-responders in this study were defined as patients who did not clear virus after a minimum of 12 weeks of SOC, including null responders, poor responders, and partial responders. Relapsers and on-treatment breakthroughs were not enrolled in the study. The most common adverse events associated with GI-5005 were injection site reactions that were generally mild and transient in nature. Discontinuation rates due to adverse events in the GI-5005 triple therapy arm were comparable to the discontinuation rates in the SOC alone arm.
"Only 4-7% of patients with genotype 1 HCV who were null, poor or partial responders to their first course of pegylated interferon-based therapy would be expected to achieve a sustained virologic response with a second course of treatment," said Dr. Pockros. "In this study, GI-5005 conferred a three-fold improvement in SVR, an important treatment effect in this challenging patient population."
Additional immunology data from the study will be presented in a poster on Tuesday November 2, 2010 by John M. Vierling, M.D., of Baylor College of Medicine. These data show that GI-5005 improved HCV-specific T cell responses 10-fold over SOC alone in patients with the IL28B T/T genotype (~20% of chronically infected patients), the subgroup most likely to fail treatment with SOC alone. Patients with the IL28B T/T genotype receiving SOC alone had an HCV-specific cellular immune response that was 17-fold lower than patients in the IL28B C/C or C/T subgroups. The improved HCV-specific T cell immunity in IL28B T/T patients receiving GI-5005 plus SOC correlates with previously reported data that demonstrated GI-5005 increased SVR rates by 60 percent in interferon-naïve T/T patients compared to T/T patients receiving SOC alone.
"These data suggest that the fundamental deficit in patients carrying the T allele of the IL28B gene is a deficit in adaptive cellular immunity, the mechanism that GI-5005 was designed to address," said David Apelian, M.D., Ph.D., Chief Medical Officer at GlobeImmune. "We are confident that GI-5005 will become a cornerstone of HCV therapy, particularly for difficult to treat populations, such as IL28B T/T patients."
A 40 patient expansion of this study in patients having the IL28B T/T genotype was initiated last week to further explore the potential treatment effect of GI-5005 in this patient population.
GI-5005 is a therapeutic vaccine candidate designed to generate HCV-specific T-cell responses and improve virologic responses in patients with chronic hepatitis C virus infection.
About GlobeImmune
GlobeImmune Inc. is a private company developing therapeutic vaccines called Tarmogens for the treatment of cancer and infectious diseases. Tarmogens generate activated killer T cells that are designed to locate and eliminate virally-infected cells and/or cancer cells. The Company's lead product candidate, GI-5005, is a Tarmogen being developed for the treatment of chronic hepatitis C virus (HCV) infection. GI-5005 is designed to complement both the current standard of care and emerging novel therapies for HCV. The Company's lead oncology program, GI-4000, targets cancers caused by mutated versions of the Ras oncoprotein. GI-4000 is being investigated in clinical trials for the treatment of pancreas cancer as well as other cancers that contain mutated Ras, including non-small cell lung cancer and colorectal cancer. In May 2009, the Company announced a global partnership with Celgene focused on the discovery, development and commercialization of multiple product candidates for the treatment of cancer.
For additional information, please visit the company's website at www.globeimmune.com.
Created Nov 4 2010 - 6:56am
Phase 2b Study Demonstrates GlobeImmune's GI-5005 HCV Therapeutic Vaccine Increases Sustained Virologic Response by 12 Percent in Patients Who Previously Failed Therapy with Standard of Care.
Additional data suggest that cellular immunity may be a fundamental deficit in hardest-to-treat IL28B T/T genotype patients and is corrected by GI-5005
Data to be presented at annual meeting of the American Association for the Study of the Liver Diseases
LOUISVILLE, Colo., October 30, 2010 - GlobeImmune Inc. today announced additional data from the GI-5005-02 Phase 2b study demonstrating that GI-5005, the Company's investigational Tarmogen® product, improved sustained virologic response (SVR) by 12% in patients with genotype 1 chronic hepatitis C virus (HCV) infection who had failed prior treatment with standard of care (SOC, pegylated-interferon alpha 2a plus ribavirin). This study suggests that GI-5005 may have the potential to be the first successful therapeutic vaccine for patients chronically infected with HCV.
Paul J. Pockros, M.D., of Scripps Clinic will deliver the oral presentation of the results in a late-breaker session at 6 p.m. EDT Monday November 1, 2010 at the 61st Annual Meeting of the American Association for the Study of the Liver Diseases (AASLD) in Boston.
On an intent-to-treat basis (subjects who received at least one dose of combination therapy), prior non-responders receiving GI-5005 plus SOC as a triple therapy had an SVR rate of 17%, compared to an SVR rate of only 5% in patients receiving SOC alone. Prior non-responders in this study were defined as patients who did not clear virus after a minimum of 12 weeks of SOC, including null responders, poor responders, and partial responders. Relapsers and on-treatment breakthroughs were not enrolled in the study. The most common adverse events associated with GI-5005 were injection site reactions that were generally mild and transient in nature. Discontinuation rates due to adverse events in the GI-5005 triple therapy arm were comparable to the discontinuation rates in the SOC alone arm.
"Only 4-7% of patients with genotype 1 HCV who were null, poor or partial responders to their first course of pegylated interferon-based therapy would be expected to achieve a sustained virologic response with a second course of treatment," said Dr. Pockros. "In this study, GI-5005 conferred a three-fold improvement in SVR, an important treatment effect in this challenging patient population."
Additional immunology data from the study will be presented in a poster on Tuesday November 2, 2010 by John M. Vierling, M.D., of Baylor College of Medicine. These data show that GI-5005 improved HCV-specific T cell responses 10-fold over SOC alone in patients with the IL28B T/T genotype (~20% of chronically infected patients), the subgroup most likely to fail treatment with SOC alone. Patients with the IL28B T/T genotype receiving SOC alone had an HCV-specific cellular immune response that was 17-fold lower than patients in the IL28B C/C or C/T subgroups. The improved HCV-specific T cell immunity in IL28B T/T patients receiving GI-5005 plus SOC correlates with previously reported data that demonstrated GI-5005 increased SVR rates by 60 percent in interferon-naïve T/T patients compared to T/T patients receiving SOC alone.
"These data suggest that the fundamental deficit in patients carrying the T allele of the IL28B gene is a deficit in adaptive cellular immunity, the mechanism that GI-5005 was designed to address," said David Apelian, M.D., Ph.D., Chief Medical Officer at GlobeImmune. "We are confident that GI-5005 will become a cornerstone of HCV therapy, particularly for difficult to treat populations, such as IL28B T/T patients."
A 40 patient expansion of this study in patients having the IL28B T/T genotype was initiated last week to further explore the potential treatment effect of GI-5005 in this patient population.
GI-5005 is a therapeutic vaccine candidate designed to generate HCV-specific T-cell responses and improve virologic responses in patients with chronic hepatitis C virus infection.
About GlobeImmune
GlobeImmune Inc. is a private company developing therapeutic vaccines called Tarmogens for the treatment of cancer and infectious diseases. Tarmogens generate activated killer T cells that are designed to locate and eliminate virally-infected cells and/or cancer cells. The Company's lead product candidate, GI-5005, is a Tarmogen being developed for the treatment of chronic hepatitis C virus (HCV) infection. GI-5005 is designed to complement both the current standard of care and emerging novel therapies for HCV. The Company's lead oncology program, GI-4000, targets cancers caused by mutated versions of the Ras oncoprotein. GI-4000 is being investigated in clinical trials for the treatment of pancreas cancer as well as other cancers that contain mutated Ras, including non-small cell lung cancer and colorectal cancer. In May 2009, the Company announced a global partnership with Celgene focused on the discovery, development and commercialization of multiple product candidates for the treatment of cancer.
For additional information, please visit the company's website at www.globeimmune.com.
Thursday, November 4, 2010
Boosted HCV proteases in the STAT-C era - what can we learn from HIV?
I'm far from a pharmacologist and nowhere near being an expert in pharmacokinetics, but my rudimentary view, based on this report Jules Levin did on a session addressing ritonavir boosted HCV PIs from the 5th International Workshop on Hepatitis C Resistance and New Compounds last summer in Boston, is that we certainly could learn a thing or two taught from the lessons of boostings past. Boosting HIV protease inhibitors with a sub-therapeutic dose of ritonavir was a break through in the fight against HIV. Boosted PIs allowed for a 'PK cushion' when it came to trough levels... that is, when the PI was at its lowest concentration in the body - usually just before the next dose - it was still well above the IC50 of the virus thanks to the metabolic inhibition provided by ritonavir. This cushion prevented sub-therapeutic levels of the drug which could lead to viral resistance. As an added benefit, this also allowed for less frequent dosing and a sometimes drastic reduction in pill count - hopefully, one could argue - leading to an improvement in patient adherence. The dark side of ritonavir boosting is the remote possibility that even a sub-therapeutic dose could lead to the development of HIV resistance, tolerability is still an issue, increased trigylcerides, kidney toxicity and the fact that an essential metabolic enzyme, CYP 450, an enzyme responsible for the metabolism of many common drugs, not just HIV protease inhibitors, was effectively being inhibited as long as the patient was on therapy. Drug-drug interactions are a major problem in boosted PI HIV therapy, and will continue to be.
So all of the above might be applicable to ritonavir-boosting of HCV protease inhibitors as well… at least some of them. Telaprevir, despite what was shown in vitro, doesn’t respond to ritonavir boosting in vivo, at least for the long haul. Experts are still speculating on the exact reasons why – perhaps an inhibition/induction mechanism on the part of Telaprevir or some secondary mechanism of metabolism. The good news is that some initial data shows Telaprevir may not actually need to be boosted in a majority of patients, still showing some remarkably good mean concentration levels at trough even with q12h dosing. What still hasn’t been shown – at least to my knowledge – is the range of intra-patient variability from that mean. From the HIV PI history books, we know that there is usually a wide range of variability when it comes to pharmacokinetics dependent on a range of host factors. Even though it looks like HCV resistance might not mean a whole lot in the long run - the jury is still out – if the risk of being on the wrong end of that PK curve can be avoided, then it should certainly be a priority to do so.
Danoprevir and ABT-450, among others, are HCV protease inhibitors that appear to benefit from ritonavir boosting or even require it. In fact, Roche changed the dosing in their INFORM-2 Phase I trial of Danoprevir to include ritonavir boosting - but we need to see more data before the final judgment. Where the therapies for HIV and HCV differ, however, is that the HCV patient will only be on a boosted PI regimen for a short period of time, vs the HIV patient who is on the drug indefinitely so some of the long term metabolic effects of being on a boosted PI may be avoided. Still, drug-drug interactions are a concern as is the safety of a patient on a boosted HCV protease inhibitor with renal and/or liver insufficiency.
Could the benefits outweigh the risks in using ritonavir to boost HCV PIs? It’s definitely a tough call at this point and any judgment would be highly theoretical given the relative shortage of data in this area. As new data emerges, we’ll get a better idea of any clinical benefit or potential safety risks for the HCV patient in this brave new era of STAT-C therapy. My semi-educated gut feeling is that boosted PIs will offer some benefit with providing a “PK cushion” thus a leg-up in preventing resistance… but will that be enough to actually prevent resistance given a rapidly replicating virus that can make every conceivable combination of mutations in the course of one day? Does a boosted HCV PI plus a nuc or non-nuke backbone present enough of a barrier to prevent resistance given the variables such as intra-patient PK variability, drug interactions and adherence issues? Will interferon and ribiviran still be needed to shore-up any gaps left by STAT-C therapy? How about next generation metabolic blockers like Gilead's Cobicistat now in development? Only time - and solid empirical data - will tell.
So all of the above might be applicable to ritonavir-boosting of HCV protease inhibitors as well… at least some of them. Telaprevir, despite what was shown in vitro, doesn’t respond to ritonavir boosting in vivo, at least for the long haul. Experts are still speculating on the exact reasons why – perhaps an inhibition/induction mechanism on the part of Telaprevir or some secondary mechanism of metabolism. The good news is that some initial data shows Telaprevir may not actually need to be boosted in a majority of patients, still showing some remarkably good mean concentration levels at trough even with q12h dosing. What still hasn’t been shown – at least to my knowledge – is the range of intra-patient variability from that mean. From the HIV PI history books, we know that there is usually a wide range of variability when it comes to pharmacokinetics dependent on a range of host factors. Even though it looks like HCV resistance might not mean a whole lot in the long run - the jury is still out – if the risk of being on the wrong end of that PK curve can be avoided, then it should certainly be a priority to do so.
Danoprevir and ABT-450, among others, are HCV protease inhibitors that appear to benefit from ritonavir boosting or even require it. In fact, Roche changed the dosing in their INFORM-2 Phase I trial of Danoprevir to include ritonavir boosting - but we need to see more data before the final judgment. Where the therapies for HIV and HCV differ, however, is that the HCV patient will only be on a boosted PI regimen for a short period of time, vs the HIV patient who is on the drug indefinitely so some of the long term metabolic effects of being on a boosted PI may be avoided. Still, drug-drug interactions are a concern as is the safety of a patient on a boosted HCV protease inhibitor with renal and/or liver insufficiency.
Could the benefits outweigh the risks in using ritonavir to boost HCV PIs? It’s definitely a tough call at this point and any judgment would be highly theoretical given the relative shortage of data in this area. As new data emerges, we’ll get a better idea of any clinical benefit or potential safety risks for the HCV patient in this brave new era of STAT-C therapy. My semi-educated gut feeling is that boosted PIs will offer some benefit with providing a “PK cushion” thus a leg-up in preventing resistance… but will that be enough to actually prevent resistance given a rapidly replicating virus that can make every conceivable combination of mutations in the course of one day? Does a boosted HCV PI plus a nuc or non-nuke backbone present enough of a barrier to prevent resistance given the variables such as intra-patient PK variability, drug interactions and adherence issues? Will interferon and ribiviran still be needed to shore-up any gaps left by STAT-C therapy? How about next generation metabolic blockers like Gilead's Cobicistat now in development? Only time - and solid empirical data - will tell.
Regulus Therapeutics receives $500,000 in grants to develop microRNA therapeutics to treat HCV & fibrosis....
From the PharmaLive.com News Archive - Nov. 03, 2010
LA JOLLA, Calif.--(BUSINESS WIRE)--Nov 3, 2010 - Regulus Therapeutics Inc. announced today that it has been awarded two grants totaling $488,989 under the Federal government's Qualifying Therapeutic Discovery Project Program. The Qualifying Therapeutic Discovery Project Program was created to support research with the potential to produce new therapies and create high paying jobs. The grant funding will support preclinical development of Regulus' novel microRNA approaches to treat Hepatitis C Virus infection and fibrosis.
“We are pleased to receive maximum awards for both of the applications we submitted to this program,” said Zachary A. Zimmerman, Ph.D., Director of Business Development at Regulus. “The funding provides access to non-dilutive capital supporting the advancement of our preclinical microRNA programs toward the clinic.”
The Qualifying Therapeutic Discovery Project Program provides an immediate boost to the U.S. biomedical research community through targeted support of projects that have the potential to produce new therapies, address unmet medical needs and create jobs.
About microRNAs
The discovery of microRNA in humans is one of the most exciting scientific breakthroughs in the last decade. microRNAs are small RNA molecules, typically 20 to 25 nucleotides in length that do not encode proteins but instead regulate gene expression. Nearly 700 microRNAs have been identified in the human genome, and more than one-third of all human genes are believed to be regulated by microRNAs. As a single microRNA can regulate entire networks of genes, these molecules are considered the master regulators of the genome. microRNAs have been shown to play an integral role in numerous biological processes including the immune response, cell-cycle control, metabolism, viral replication, stem cell differentiation and human development. Most microRNAs are conserved across multiple species indicating the evolutionary importance of these molecules as modulators of critical biological pathways. Indeed, microRNA expression or function has been shown to be significantly altered in many disease states, including cancer, heart failure and viral infections. Targeting microRNAs with anti-miRs, antisense oligonucleotide inhibitors of microRNAs, or miR-mimics, double-stranded oligonucleotides to replace microRNA function, opens the possibility of a novel class of therapeutics and a unique approach to treating disease by modulating entire biological pathways. To learn more about microRNAs please visit http://www.regulusrx.com/microrna/microrna-explained.php
About Regulus Therapeutics Inc.
Regulus Therapeutics is a biopharmaceutical company leading the discovery and development of innovative new medicines targeting microRNAs. Regulus is using a mature therapeutic platform based on technology that has been developed over 20 years and tested in greater than 5,000 human subjects. In addition, Regulus works with a broad network of academic collaborators and leverages oligonucleotide drug discovery and development expertise from its founding companies Alnylam Pharmaceuticals (Nasdaq:ALNY) and Isis Pharmaceuticals (Nasdaq:ISIS). Regulus is advancing microRNA therapeutics towards the clinic in several areas including hepatitis C infection, immuno-inflammatory diseases, fibrosis, oncology, and cardiovascular/metabolic diseases. Regulus' intellectual property estate contains both the fundamental and core patents in the field and includes over 600 patents and more than 300 pending patent applications pertaining primarily to chemical modifications of oligonucleotides targeting microRNAs for therapeutic applications. In April 2008, Regulus entered into a major alliance with GlaxoSmithKline to discover and develop microRNA therapeutics for immuno-inflammatory diseases. In February 2010, Regulus entered into a new collaboration with GlaxoSmithKline to develop and commercialize microRNA therapeutics targeting microRNA-122 for the treatment of Hepatitis C Viral infection. In June 2010, sanofi-aventis and Regulus entered into the largest-to-date strategic alliance for the development of microRNA therapeutics. This alliance is focused initially on fibrosis. For more information, visit http://www.regulusrx.com
LA JOLLA, Calif.--(BUSINESS WIRE)--Nov 3, 2010 - Regulus Therapeutics Inc. announced today that it has been awarded two grants totaling $488,989 under the Federal government's Qualifying Therapeutic Discovery Project Program. The Qualifying Therapeutic Discovery Project Program was created to support research with the potential to produce new therapies and create high paying jobs. The grant funding will support preclinical development of Regulus' novel microRNA approaches to treat Hepatitis C Virus infection and fibrosis.
“We are pleased to receive maximum awards for both of the applications we submitted to this program,” said Zachary A. Zimmerman, Ph.D., Director of Business Development at Regulus. “The funding provides access to non-dilutive capital supporting the advancement of our preclinical microRNA programs toward the clinic.”
The Qualifying Therapeutic Discovery Project Program provides an immediate boost to the U.S. biomedical research community through targeted support of projects that have the potential to produce new therapies, address unmet medical needs and create jobs.
About microRNAs
The discovery of microRNA in humans is one of the most exciting scientific breakthroughs in the last decade. microRNAs are small RNA molecules, typically 20 to 25 nucleotides in length that do not encode proteins but instead regulate gene expression. Nearly 700 microRNAs have been identified in the human genome, and more than one-third of all human genes are believed to be regulated by microRNAs. As a single microRNA can regulate entire networks of genes, these molecules are considered the master regulators of the genome. microRNAs have been shown to play an integral role in numerous biological processes including the immune response, cell-cycle control, metabolism, viral replication, stem cell differentiation and human development. Most microRNAs are conserved across multiple species indicating the evolutionary importance of these molecules as modulators of critical biological pathways. Indeed, microRNA expression or function has been shown to be significantly altered in many disease states, including cancer, heart failure and viral infections. Targeting microRNAs with anti-miRs, antisense oligonucleotide inhibitors of microRNAs, or miR-mimics, double-stranded oligonucleotides to replace microRNA function, opens the possibility of a novel class of therapeutics and a unique approach to treating disease by modulating entire biological pathways. To learn more about microRNAs please visit http://www.regulusrx.com/microrna/microrna-explained.php
About Regulus Therapeutics Inc.
Regulus Therapeutics is a biopharmaceutical company leading the discovery and development of innovative new medicines targeting microRNAs. Regulus is using a mature therapeutic platform based on technology that has been developed over 20 years and tested in greater than 5,000 human subjects. In addition, Regulus works with a broad network of academic collaborators and leverages oligonucleotide drug discovery and development expertise from its founding companies Alnylam Pharmaceuticals (Nasdaq:ALNY) and Isis Pharmaceuticals (Nasdaq:ISIS). Regulus is advancing microRNA therapeutics towards the clinic in several areas including hepatitis C infection, immuno-inflammatory diseases, fibrosis, oncology, and cardiovascular/metabolic diseases. Regulus' intellectual property estate contains both the fundamental and core patents in the field and includes over 600 patents and more than 300 pending patent applications pertaining primarily to chemical modifications of oligonucleotides targeting microRNAs for therapeutic applications. In April 2008, Regulus entered into a major alliance with GlaxoSmithKline to discover and develop microRNA therapeutics for immuno-inflammatory diseases. In February 2010, Regulus entered into a new collaboration with GlaxoSmithKline to develop and commercialize microRNA therapeutics targeting microRNA-122 for the treatment of Hepatitis C Viral infection. In June 2010, sanofi-aventis and Regulus entered into the largest-to-date strategic alliance for the development of microRNA therapeutics. This alliance is focused initially on fibrosis. For more information, visit http://www.regulusrx.com
Tuesday, November 2, 2010
Biolex presents positive tolerability data of Locteron vs Peg-Intron at AASLD...
Market Wire - Nov. 01, 2010
PITTSBORO, NC -- (MARKET WIRE) -- 11/01/10 -- Biolex Therapeutics, Inc. today announced positive results from two Phase 2b trials further demonstrating the strong anti-viral response and tolerability advantages of the 480 µg dose of Locteron® in the treatment of hepatitis C. In the Phase 2b trials, patients directly reported flu-like adverse events on a daily basis through an electronic patient-reported outcome (ePRO) system, and the results demonstrated a statistically significant reduction in the frequency and severity of flu-like adverse events and reduced use of concomitant (analgesic/antipyretic) medications for patients treated with Locteron compared to patients treated with the PEG-Intron® control. Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently marketed interferons as a core component of combination therapies for the treatment of hepatitis C. These advantages include reduced flu-like symptoms, reduced rates of depression, and a less frequent dosing regimen with half the number of injections. The "EMPOWER" Phase 2b ePRO results will be presented today in a late-breaker session at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.
EMPOWER is a prospectively designed analysis of the combined results from two Phase 2b hepatitis C trials focusing on the 480 µg dose of Locteron (the middle dose of three Locteron doses evaluated in the two trials). Through 12 weeks of treatment, 50% of the patients in the Locteron 480 µg group achieved cEVR (undetectable HCV RNA) compared to 46% of the patients in the PEG-Intron group. As a result of its controlled-release mechanism, Locteron achieved strong efficacy results while being dosed half as frequently as PEG-Intron.
The AASLD presentation today includes for the first time results from the ePRO adverse-event reporting system where patients directly recorded their flu-like adverse events on a daily basis, providing greater insight into the patients' real world experiences with these side effects and the impact on their daily activities. In addition to the self-reporting by patients with the ePRO system, flu-like adverse events were also recorded using traditional weekly adverse event assessments performed by the clinical sites. Flu-like adverse events were predefined to include arthralgia, chills, fever, headache, and myalgia.
A substantial reduction in flu-like adverse events for patients treated with Locteron compared to PEG-Intron was evident even in the first week after initiation of treatment and continued through the 12-week time point through which the ePRO system was utilized. The reduction in flu-like adverse events during the week after the first injection supports the hypothesis that the slower rise to Cmax provided by the controlled-release mechanism of Locteron contributes to the tolerability advantages seen in multiple clinical trials. A comparison of the flu-like adverse event reporting by the clinical sites and by ePRO provide independent confirmation of the substantial benefits Locteron provided in reducing these side effects as outlined in the table below:
Locteron Reduction in Flu-Like Adverse Events (Week 1)
---------------------------------------------------------
Total Events Moderate and Severe Events
---------------------------- ----------------------------
Clinical Site Patient (ePRO) Clinical Site Patient (ePRO)
Reporting Self-Reporting Reporting Self-Reporting
------------- -------------- ------------- --------------
Locteron Reduction 50% 51% 70% 39%
In Flu-Like Adverse Reduction Reduction Reduction Reduction
Events Compared to
PEG-Intron
"The ePRO results being presented for the first time today are robust and provide important insight into the impact that flu-like adverse events have on patients' daily lives," said Patrick Marcellin, MD, PhD, Professor of Hepatology at the University of Paris and Head of the Viral Hepatitis Research Unit in Hôpital Beaujon, Clichy. "Treatment of hepatitis C is likely to progress to triple and quad therapies in which interferons are combined with one or more direct-acting anti-viral drugs. Locteron's advantages with regards to flu-like adverse events, depression and dosing frequency have the potential to enhance the overall tolerability of, and patient adherence to, these future combinations."
Consistent with the reduction in flu-like adverse events, less than half as many Locteron patients used concomitant medications (analgesics and antipyretics) compared to the usage of these medications by PEG-Intron patients during the study period as detailed below.
Percentage of Patients Using
Concomitant Medications
-----------------------------------------
Locteron
480 µg PEG-Intron
-------------------- --------------------
Patients Using Analgesics 27% 59%
Patients Using Antipyretics 23% 49%
A comparison of the ePRO and clinic site reporting highlights the fact that flu-like adverse events may even be more important to patients than historically believed. The total flu-like adverse events reported directly by the patients using the ePRO system during the first 12 weeks of EMPOWER was more than four times greater than the total flu-like adverse events recorded by the clinical sites. Also of importance, patients rated 80% of their flu-like adverse events as moderate or severe in their ePRO reports, compared to the clinical site reporting in which only 13% of flu-like adverse events were rated as moderate or severe. Despite the apparent differences in sensitivity in the two adverse event reporting methods, the results from both the ePRO and weekly clinic visits independently confirm the reduction in flu-like adverse events for patients treated with Locteron compared to patients treated with PEG-Intron. Through the 12-weeks, the difference in flu-like adverse event counts was statistically significant when measured by both the ePRO and clinical site reporting methods (p < 0.001 for each).
The relevance of flu-like adverse events was highlighted in a survey of hepatitis C patients published in the Journal of Viral Hepatitis in June 2010 in which depression and flu-like symptoms were cited as the two most important adverse events impacting patient adherence to treatment. Last week Biolex reported 48-week results from its SELECT-2 Phase 2b trial of Locteron demonstrating substantial reductions in depression compared to PEG-Intron.
AASLD Presentation
The EMPOWER ePRO and clinical-site tolerability results will be presented today by the lead author, Walker Long, MD, Chief Medical Officer and Vice President, Drug Development, Biolex Therapeutics, in the form of a poster titled "Adverse Event Reporting During HCV Treatment Via Weekly Clinic Visits Substantially Underestimates Flu Frequency & Severity Compared to Daily ePRO: Results From 133 Patients in EMPOWER."
"The EMPOWER results are notable in that they show a statistically significant reduction of flu-like adverse events for Locteron confirmed by two sources, the clinical site assessments and the daily patient reporting of side effects through the ePRO System. The reductions in the percent of patients using analgesics and in overall analgesic use observed in the Locteron group provide additional support for improved tolerability on Locteron," said Dr. Long. "These results complement the positive results released last week from our SELECT-2 Phase 2b trial in which we showed statistically significant reductions in flu-like adverse events for three different Locteron doses, and substantial reductions in depression for the Locteron 480 and 320 µg doses."
About EMPOWER Study
The objective of the EMPOWER study was to test the hypothesis that the 480 µg dose of Locteron dosed once every two weeks reduces flu-like symptoms but retains equivalent efficacy compared to PEG-Intron (1.5 µg/kg, administered every week). The 133 patients in the EMPOWER study were enrolled in two contributing Phase 2b trials:
* SELECT-2, a Phase 2b dose-finding trial evaluating the 320, 480 or 640 µg doses of Locteron versus PEG-Intron.
* The 480 STUDY, a Phase 2b trial evaluating the 480 µg dose of Locteron versus PEG-Intron.
All patients in both trials were treatment-naïve-genotype-1 subjects with chronic hepatitis C, and all patients were also treated with weight-based ribavirin. A total of 30 sites participated in the two trials (14 sites in the US, 11 in Europe, and five in Israel).
Locteron Overview
Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently approved products, including reduced flu-like symptoms and rates of depression, and cutting in half the number of injections required. In contrast to Locteron, the currently approved products, Pegasys® and PEG-Intron, are immediate-release products that lack a controlled-release mechanism. The two-drug combination of interferon alpha and ribavirin serves as the current standard of care for the treatment of hepatitis C. The launch of the first direct-acting anti-viral (DAA) product, projected for 2011, will transform treatment of genotype-1 patients to a triple-drug therapy (interferon plus ribavirin plus DAA) and substantially raise cure rates. Other recent triple or quad drug combinations with interferon (including interferon plus ribavirin plus two DAA agents) have shown promise in early clinical testing, further solidifying the continued role of interferon in the treatment of hepatitis C. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.
Locteron incorporates an advanced controlled-release drug delivery technology that allows dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron's controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons. This controlled-release mechanism is designed to reduce the frequency and severity of flu-like symptoms and depression commonly experienced by patients treated with pegylated interferons.
Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.
PITTSBORO, NC -- (MARKET WIRE) -- 11/01/10 -- Biolex Therapeutics, Inc. today announced positive results from two Phase 2b trials further demonstrating the strong anti-viral response and tolerability advantages of the 480 µg dose of Locteron® in the treatment of hepatitis C. In the Phase 2b trials, patients directly reported flu-like adverse events on a daily basis through an electronic patient-reported outcome (ePRO) system, and the results demonstrated a statistically significant reduction in the frequency and severity of flu-like adverse events and reduced use of concomitant (analgesic/antipyretic) medications for patients treated with Locteron compared to patients treated with the PEG-Intron® control. Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently marketed interferons as a core component of combination therapies for the treatment of hepatitis C. These advantages include reduced flu-like symptoms, reduced rates of depression, and a less frequent dosing regimen with half the number of injections. The "EMPOWER" Phase 2b ePRO results will be presented today in a late-breaker session at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.
EMPOWER is a prospectively designed analysis of the combined results from two Phase 2b hepatitis C trials focusing on the 480 µg dose of Locteron (the middle dose of three Locteron doses evaluated in the two trials). Through 12 weeks of treatment, 50% of the patients in the Locteron 480 µg group achieved cEVR (undetectable HCV RNA) compared to 46% of the patients in the PEG-Intron group. As a result of its controlled-release mechanism, Locteron achieved strong efficacy results while being dosed half as frequently as PEG-Intron.
The AASLD presentation today includes for the first time results from the ePRO adverse-event reporting system where patients directly recorded their flu-like adverse events on a daily basis, providing greater insight into the patients' real world experiences with these side effects and the impact on their daily activities. In addition to the self-reporting by patients with the ePRO system, flu-like adverse events were also recorded using traditional weekly adverse event assessments performed by the clinical sites. Flu-like adverse events were predefined to include arthralgia, chills, fever, headache, and myalgia.
A substantial reduction in flu-like adverse events for patients treated with Locteron compared to PEG-Intron was evident even in the first week after initiation of treatment and continued through the 12-week time point through which the ePRO system was utilized. The reduction in flu-like adverse events during the week after the first injection supports the hypothesis that the slower rise to Cmax provided by the controlled-release mechanism of Locteron contributes to the tolerability advantages seen in multiple clinical trials. A comparison of the flu-like adverse event reporting by the clinical sites and by ePRO provide independent confirmation of the substantial benefits Locteron provided in reducing these side effects as outlined in the table below:
Locteron Reduction in Flu-Like Adverse Events (Week 1)
---------------------------------------------------------
Total Events Moderate and Severe Events
---------------------------- ----------------------------
Clinical Site Patient (ePRO) Clinical Site Patient (ePRO)
Reporting Self-Reporting Reporting Self-Reporting
------------- -------------- ------------- --------------
Locteron Reduction 50% 51% 70% 39%
In Flu-Like Adverse Reduction Reduction Reduction Reduction
Events Compared to
PEG-Intron
"The ePRO results being presented for the first time today are robust and provide important insight into the impact that flu-like adverse events have on patients' daily lives," said Patrick Marcellin, MD, PhD, Professor of Hepatology at the University of Paris and Head of the Viral Hepatitis Research Unit in Hôpital Beaujon, Clichy. "Treatment of hepatitis C is likely to progress to triple and quad therapies in which interferons are combined with one or more direct-acting anti-viral drugs. Locteron's advantages with regards to flu-like adverse events, depression and dosing frequency have the potential to enhance the overall tolerability of, and patient adherence to, these future combinations."
Consistent with the reduction in flu-like adverse events, less than half as many Locteron patients used concomitant medications (analgesics and antipyretics) compared to the usage of these medications by PEG-Intron patients during the study period as detailed below.
Percentage of Patients Using
Concomitant Medications
-----------------------------------------
Locteron
480 µg PEG-Intron
-------------------- --------------------
Patients Using Analgesics 27% 59%
Patients Using Antipyretics 23% 49%
A comparison of the ePRO and clinic site reporting highlights the fact that flu-like adverse events may even be more important to patients than historically believed. The total flu-like adverse events reported directly by the patients using the ePRO system during the first 12 weeks of EMPOWER was more than four times greater than the total flu-like adverse events recorded by the clinical sites. Also of importance, patients rated 80% of their flu-like adverse events as moderate or severe in their ePRO reports, compared to the clinical site reporting in which only 13% of flu-like adverse events were rated as moderate or severe. Despite the apparent differences in sensitivity in the two adverse event reporting methods, the results from both the ePRO and weekly clinic visits independently confirm the reduction in flu-like adverse events for patients treated with Locteron compared to patients treated with PEG-Intron. Through the 12-weeks, the difference in flu-like adverse event counts was statistically significant when measured by both the ePRO and clinical site reporting methods (p < 0.001 for each).
The relevance of flu-like adverse events was highlighted in a survey of hepatitis C patients published in the Journal of Viral Hepatitis in June 2010 in which depression and flu-like symptoms were cited as the two most important adverse events impacting patient adherence to treatment. Last week Biolex reported 48-week results from its SELECT-2 Phase 2b trial of Locteron demonstrating substantial reductions in depression compared to PEG-Intron.
AASLD Presentation
The EMPOWER ePRO and clinical-site tolerability results will be presented today by the lead author, Walker Long, MD, Chief Medical Officer and Vice President, Drug Development, Biolex Therapeutics, in the form of a poster titled "Adverse Event Reporting During HCV Treatment Via Weekly Clinic Visits Substantially Underestimates Flu Frequency & Severity Compared to Daily ePRO: Results From 133 Patients in EMPOWER."
"The EMPOWER results are notable in that they show a statistically significant reduction of flu-like adverse events for Locteron confirmed by two sources, the clinical site assessments and the daily patient reporting of side effects through the ePRO System. The reductions in the percent of patients using analgesics and in overall analgesic use observed in the Locteron group provide additional support for improved tolerability on Locteron," said Dr. Long. "These results complement the positive results released last week from our SELECT-2 Phase 2b trial in which we showed statistically significant reductions in flu-like adverse events for three different Locteron doses, and substantial reductions in depression for the Locteron 480 and 320 µg doses."
About EMPOWER Study
The objective of the EMPOWER study was to test the hypothesis that the 480 µg dose of Locteron dosed once every two weeks reduces flu-like symptoms but retains equivalent efficacy compared to PEG-Intron (1.5 µg/kg, administered every week). The 133 patients in the EMPOWER study were enrolled in two contributing Phase 2b trials:
* SELECT-2, a Phase 2b dose-finding trial evaluating the 320, 480 or 640 µg doses of Locteron versus PEG-Intron.
* The 480 STUDY, a Phase 2b trial evaluating the 480 µg dose of Locteron versus PEG-Intron.
All patients in both trials were treatment-naïve-genotype-1 subjects with chronic hepatitis C, and all patients were also treated with weight-based ribavirin. A total of 30 sites participated in the two trials (14 sites in the US, 11 in Europe, and five in Israel).
Locteron Overview
Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently approved products, including reduced flu-like symptoms and rates of depression, and cutting in half the number of injections required. In contrast to Locteron, the currently approved products, Pegasys® and PEG-Intron, are immediate-release products that lack a controlled-release mechanism. The two-drug combination of interferon alpha and ribavirin serves as the current standard of care for the treatment of hepatitis C. The launch of the first direct-acting anti-viral (DAA) product, projected for 2011, will transform treatment of genotype-1 patients to a triple-drug therapy (interferon plus ribavirin plus DAA) and substantially raise cure rates. Other recent triple or quad drug combinations with interferon (including interferon plus ribavirin plus two DAA agents) have shown promise in early clinical testing, further solidifying the continued role of interferon in the treatment of hepatitis C. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.
Locteron incorporates an advanced controlled-release drug delivery technology that allows dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron's controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons. This controlled-release mechanism is designed to reduce the frequency and severity of flu-like symptoms and depression commonly experienced by patients treated with pegylated interferons.
Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.
Monday, November 1, 2010
Kadmon and Valeant ink global deal on ribavirn and taribavirin....
Valeant Pharmaceuticals and Kadmon Pharmaceuticals inked two separate agreements, worth a combined $12.5 million up front, covering the development and/or marketing of the hepatitis C drug ribavirin and the clinical-stage ribavirin prodrug candidate taribavirin. The deals come within a few days of Kadmon buying out Three Rivers Pharmaceuticals, which already markets the hepatitis C drugs Infergen™ (consensus interferon), Ribasphere® (ribavirin, USP), and RibaPak® (ribavirin).
The first new deal gives Kadmon an exclusive, worldwide license (excluding Japan) to taribavirin, which has successfully completed a Phase IIb trial for the treatment of chronic hepatitis C. Under terms of this agreement Kadmon will pay Valeant $5 million up front in addition to development milestones and future sales royalties.
The second agreement gives Valeant exclusive rights to all Kadmon dosage forms of ribavirin, including its 200 mg, 400 mg, and 600 mg capsules and tablets, in Poland, Hungary, the Czech Republic, Slovakia, Romania, and Bulgaria. Valeant paid Kadmon $7.5 million for the ribavirin portfolio and will source the products from Kadmon.
At first glance the combination of these two deals may seem counterintuitive. Valeant is passing further development of its ribavirin prodrug candidate virtually worldwide to Kadmon but is instead taking on rights to a marketed ribavirin portfolio in central Europe. However, as Valeant’s CEO, J. Michael Pearson, points out, while further development of taribavirin in house was halted in 2009 until a partner could be found, the firm wants to keep its hand in the branded generics market for hepatitis C drugs in some territories. “While participating in product development in the overall hepatitis C market no longer fits within our corporate development strategy, ribavirin could be a significant product for our branded generics portfolio in Central Europe.”
Kadmon, meanwhile, is making a more obvious push into the hepatitis C market globally, both through its deal with Valeant and with its recent acquisition of Three Rivers. “Kadmon is building upon its commercial platform in hepatitis C through expanded global distribution and the addition of complementary products,” notes Samuel D. Kalsal, CEO. “Our agreements with Valeant achieve milestones for both of these objectives. Taribavirin completes our ribavirin franchise and will ensure its future sustainability and growth. We have also expanded our global distribution network for ribavirin into markets in which Valeant is a leading provider.”
The first new deal gives Kadmon an exclusive, worldwide license (excluding Japan) to taribavirin, which has successfully completed a Phase IIb trial for the treatment of chronic hepatitis C. Under terms of this agreement Kadmon will pay Valeant $5 million up front in addition to development milestones and future sales royalties.
The second agreement gives Valeant exclusive rights to all Kadmon dosage forms of ribavirin, including its 200 mg, 400 mg, and 600 mg capsules and tablets, in Poland, Hungary, the Czech Republic, Slovakia, Romania, and Bulgaria. Valeant paid Kadmon $7.5 million for the ribavirin portfolio and will source the products from Kadmon.
At first glance the combination of these two deals may seem counterintuitive. Valeant is passing further development of its ribavirin prodrug candidate virtually worldwide to Kadmon but is instead taking on rights to a marketed ribavirin portfolio in central Europe. However, as Valeant’s CEO, J. Michael Pearson, points out, while further development of taribavirin in house was halted in 2009 until a partner could be found, the firm wants to keep its hand in the branded generics market for hepatitis C drugs in some territories. “While participating in product development in the overall hepatitis C market no longer fits within our corporate development strategy, ribavirin could be a significant product for our branded generics portfolio in Central Europe.”
Kadmon, meanwhile, is making a more obvious push into the hepatitis C market globally, both through its deal with Valeant and with its recent acquisition of Three Rivers. “Kadmon is building upon its commercial platform in hepatitis C through expanded global distribution and the addition of complementary products,” notes Samuel D. Kalsal, CEO. “Our agreements with Valeant achieve milestones for both of these objectives. Taribavirin completes our ribavirin franchise and will ensure its future sustainability and growth. We have also expanded our global distribution network for ribavirin into markets in which Valeant is a leading provider.”
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