Showing posts with label HCV protease inhibitor. Show all posts
Showing posts with label HCV protease inhibitor. Show all posts
Monday, May 21, 2012
Achillion discloses additional data on HCV protease inhibitor ACH-2684
Posted on 5/21/12 via MarketWatch.com. Look what happens when I go away for a week. The CDC changes it's guidelines to include one-time HCV testing for Baby Boomers (FYI, HCV drug developers had a hand in shaping this shift in public policy via the Viral Hepatitis Action Coalition for all you fans of government-corporate relationships) and Achillion continues to shore up their pipeline with decent drugs. OK, so a 3.73 log10 drop isn't exactly Telaprevir-like, but given the right backbone regimen - hopefully one also developed and manufactured by this currently unpartnered company - Achillion could hit it big.
Achillion Announces Additional Proof-of-Concept Data With ACH-2684 for the Treatment of Hepatitis C
Achieves Up to 3.73 log10 Reduction in Genotype 1 HCV RNA After Three Days of Treatment With Once-Daily 400 mg ACH-2684 in Phase 1b Study
NEW HAVEN, Conn., May 21, 2012 (GlobeNewswire via COMTEX) -- Achillion Pharmaceuticals, Inc. ACHN +10.92% today reported proof-of-concept data from a Phase 1b clinical trial demonstrating that patients with chronic hepatitis C (HCV) genotype 1 (GT 1) treated with ACH-2684, a second-generation protease inhibitor, achieved a mean maximum 3.73 log10 reduction in HCV RNA after three-day 400 mg monotherapy with once-daily (QD) dosing. The compound also demonstrated good safety and tolerability both in healthy volunteers and in patients with HCV.
"We believe ACH-2684, with its potent antiviral activity achieved without boosting and once-daily dosing, is one of the most intriguing protease inhibitors in clinical development for the treatment of HCV," commented Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "As we continue to focus our efforts on advancing our internally developed all-oral, interferon-free HCV regimen consisting of ACH-1625, our next generation protease inhibitor, in combination with ACH-3102, a second generation pan-genotypic NS5A inhibitor, we believe that the profile of ACH-2684 provides a significant strategic and therapeutic option for potential combinations with either ACH-3102 or other direct-acting antiviral agents."
ACH-2684 Phase 1 Clinical Trial
Achillion is evaluating ACH-2684 in a Phase 1 randomized, double-blind, placebo-controlled clinical trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity in healthy subjects and HCV-infected patients. The trial consists of three segments: Phase 1a assessment of single ascending oral doses (SAD) in healthy volunteers, Phase 1a 14-day multiple ascending doses segment (MAD) in healthy volunteers, and Phase 1b evaluation of three days of oral repeat doses in subjects with GT 1 or 3 HCV. The MAD segment of this trial will be initiated during the second quarter and full trial results are expected to be presented at a medical meeting in the fourth quarter of 2012.
During the oral repeat doses segment in subjects infected with GT 1 HCV, a total of 30 patients were enrolled including 6 patients receiving placebo and 24 patients treated with three doses of 100 mg once daily (n=8), 400 mg once daily (n=8), or 400 mg twice daily (n=8) of ACH-2684. No serious adverse events (SAE) were reported and there were no patient discontinuations during treatment. The mean maximum GT 1 HCV RNA decline during therapy for the 100 mg QD, 400 mg QD, and 400 mg BID groups were 3.36 log10, 3.73 log10, and 4.16 log10, respectively, compared to a 0.68 log10 decline for patients receiving placebo. There were no viral breakthroughs observed during ACH-2684 monotherapy. Additional assessments of GT 3 activity are currently under development.
Safety data from the SAD and HCV-infected segments of the trial demonstrated ACH-2684 was well tolerated at all doses evaluated up to and including the maximum total daily dose of 1400 mg. There were no serious adverse events, no clinically significant changes in vital signs, electrocardiograms (ECGs), or laboratory evaluations. All reported adverse events were classified as mild or moderate, and were transient in nature. Dosing in the 14-day MAD segment is being initiated during the second quarter with longer term safety data expected to be available in the third quarter of 2012.
About ACH-2684
ACH-2684 is a next-generation HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-2684 is a macro-cyclic, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-2684 demonstrated pico-molar potency, excellent pharmacokinetic properties and safety profile at high drug exposures. ACH-2684 also exhibits rapid and extensive partitioning to the liver, as well as high liver/plasma ratios in preclinical studies. ACH-2684 has shown pico-molar potency against NS3 protease that is specific to HCV. It has preclinical activity against the 6 known genotypes of HCV and exhibits equipotent activity against HCV genotypes 1a and 1b at an IC50 of approximately 100 pico-molar. The drug candidate was discovered internally and is being advanced by Achillion.
About HCV
The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide including more than 5 million people in the United States, more than twice as widespread as HIV. Three-fourths of the HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.
About Achillion Pharmaceuticals
Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.
Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the potency, safety, tolerability, effectiveness and other characteristics of Achillion's ACH-2684, ACH-1625 and ACH-3102; Achillion's expectations regarding timing for the commencement, completion and reporting of results of clinical trials of drug candidates including ACH-2684, ACH-1625 and ACH-3102; and Achillion's ability to advance a potentially best-in-class all-oral, interferon-free combination of ACH-1625 and ACH-3102 and ACH-2684 in combination with ACH-3102 or other direct acting antiviral agents. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: replicate in later clinical trials positive results found in earlier stage nonclinical studies and clinical trials of ACH-2684, ACH-1625 and ACH-3102; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2011 and its subsequent SEC filings.
In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any obligation to update any forward-looking statement, except as required by applicable law.
This news release was distributed by GlobeNewswire, www.globenewswire.com
SOURCE: Achillion Pharmaceuticals, Inc.
CONTACT: Company Contact:
Glenn Schulman
Achillion Pharmaceuticals, Inc.
Tel. (203) 624-7000
gschulman@achillion.com
Investors:
Mary Kay Fenton
Achillion Pharmaceuticals, Inc.
Tel. (203) 624-7000
mfenton@achillion.com
Media:
Christin Culotta Miller
Ogilvy PR
Tel. (212) 880-5264
Christin.Miller@Ogilvy.com
Monday, February 27, 2012
Wall Street Journal - "Medivir Vies For Spot In Narrow Hepatitis C Market"
Posted 2/27/12 in the Wall Street Journal: Now here's a corporate leader with some confidence, bordering on cockiness, which, arguably is what coporate leaders should have copious amounts of. Even if it's bluster. Medivir Executive Vice-President of Corporate Affairs Rein Piir tells Dow Jones that "there is nothing in development that's better than TMC435, which is currently in global Phase III trials and which Medivir expects to launch by the end of next year." This puts TMC435, if he's right, to be potentially the first 2nd generation DAA to hit the market, at least ex-US.
By Simon Varcoe
Of DOW JONES NEWSWIRES
LONDON (Dow Jones)--Hepatitis C, a harrowing infection that leads to the inflammation of the liver, is a virus of pandemic size that has attracted the attention of some of the world's biggest drug makers.
But Sweden's small biotech Medivir AB (MVIR-B.SK) says it intends to be a major player in treating the disease, and predicts the market will ultimately have room for just four or five products.
"It is simply a question of which drug will have the biggest share of the market", Medivir's executive vice-president of corporate affairs Rein Piir told Dow Jones Newswires in an interview.
And in protease inhibitor TMC435, Piir believes Medivir has found its winner.
Piir says there is nothing in development that's better than TMC435, which is currently in global Phase III trials and which Medivir expects to launch by the end of next year.
Danske Banke analyst Hans Jeppsson agrees.
Jeppsson regards TMC435 as being the best-in-class protease inhibitor, which prevents viral replication by inhibiting the activity of protease enzymes. Final judgment will need to await results from two combination trials the drug is currently undergoing, he adds.
Around 170 million people are infected worldwide with Hepatitis C, a disease that can be transmitted sexually, through shared needles or through infected blood transfusions.
Thousands of people in Japan were infected with Hepatitis C between the 1970s and 1990s due to tainted blood clotting agents and the country remains one of the most hepatitis C-dense in the world. Due to the high numbers of hepatitis C sufferers in Japan, the country is "as important commercially" to Medivir as Europe, Piir says.
Other countries with a high prevalence of Hepatitis C include Egypt, where around 20% of blood donors are anti-HCV positive, and areas of Italy.
Medivir's Piir believes that the future treatment of Hepatitis C will involve a combination of protease inhibitors; inhibitors of nucleotides, which are molecules that, when joined together, make up the structural units of RNA and DNA; and inhibitors of NS5A, a non structural viral protein found in Hepatitis C.
NS5A inhibitors currently in development include Bristol-Myers Squibb's (BMY) BMS790052, and Gilead Sciences Inc's (GILD) GS-7977. However, Gilead recently reported that a majority of patients in a clinical trial of GS-7977 had experienced a relapse in their disease after being treated with the product, raising questions about the market potential of the drug and the wider class of NS5A inhibitors.
A protease inhibitor currently used to treat HCV genotype 1 infection, the most common and hardest-to-treat type of Hepatitis C is Vertex Pharmaceuticals' (VRTX) and Johnson & Johnson's (JNJ) telaprevir, though, unlike TMC435, it must be administered in combination with pegylated interferon alpha and the antiviral drug ribavirin. Its safety profile has also been criticized, whereas TMC435 has to-date been generally safe and well tolerated, according to Medivir.
The Swedish biotech floated on the Nasdaq OMX Stockholm index in 1996 and currently has a market capitalization of around SEK2.1 billion ($320.2 million).
-By Simon Varcoe, Dow Jones Newswires; +44-20-7842-9449; simon.varcoe@dowjones.com
Wednesday, January 11, 2012
Achillion Pharmaceuticals updates investors on HCV protease inhibitor portfolio...
From RTT News: Short blurb on Achillion's HCV protease inhibitor portfolio - ACH-1625 and ACH-2684
Achillion Pharmaceuticals (ACHN) Rose Above Resistance At The Highs
1/10/2012 6:51 AM ET
(RTTNews) - Achillion Pharmaceuticals (ACHN: News ) reported new clinical trial results on its portfolio of protease inhibitors Monday morning. Based upon the results, the company is planning further exploration of ACH-1625 in combination with other oral antiviral agents for the treatment of all HCV genotypes and continues to evaluate ACH-2684 in a Phase 1 clinical trial.
Achillion Pharmaceuticals gapped open higher Monday and climbed further around the middle of the afternoon. The stock finished up by 1.80 at $9.72, with volume at a 6-month high. Achillion broke out of a 2 1/2 week range and set a new high for the year.
Wednesday, December 14, 2011
Boehringer Ingelheim enrolls final patient in BI 210335 HCV protease inhibitor phase III trial....
The race for the 2nd generation of HCV Direct Acting Antivirals continues to be too close to call, with BI's BI 210335 HCV protease inhibitor finalizing it's last patient for it's phase III trial. The asute observer of the HCV marketplace will recall the interim results of BI's SOUND-C2 trial looking at the interferon-free combo of BI 201335 and BI's BI 207127 polymerase inhibitor in genotype 1 tx-naive patients. At week 12, 76% of patients had VR with a respectable 63% of patients achieved SVR12.
From Medical News Today
Boehringer Ingelheim Completes Patient Entry For Phase III Trial Program In Hepatitis C
12 Dec 2011
According to Boehringer Ingelheim's announcement, the company's large-scale Phase III clinical trial program for BI210335, an investigational, oral protease inhibitor for the treatment of chronic hepatitis C virus (HCV) has randomized the final patient for treatment.
Their current extensive trial program is conducted in 15 countries, with key regions in the E.U., Japan, the U.S., Canada, Korea, Taiwan and Russia at over 350 sites and involves almost 2,000 treatment-experienced and treatment-naïve patients overall.
The program's three Phase III trials will be carried out to assess BI 201335 combined with the golden standard treatment of pegylated interferon (pegIFN) and ribavirin (RBV) in patients with chronic genotype-1 HCV. The majority of HCV patients infected with the genotype 1 virus are amongst the most difficult patient groups to treat. The study program's primary clinical endpoint is the assessment of "sustained viral response" (SVR), considered to be a viral cure, with results from the Phase III trials expected in the first half of 2013.
The complete BI 201335 program was awarded a Fast Track designation by the FDA. The U.S. Food and Drug Administration has designed the Fast Track process to enable the development and review process of important new drugs to treat serious diseases more rapidly than usual to fill an unmet medical need.
Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim said: "We are progressing our BI 201335 program with a high priority to leverage its potential to improve cure rates in HCV treatment. We believe our HCV-pipeline may become an important tool to fight a chronic disease that affects over 170 million people worldwide."
Last month at the American Association for the Study of Liver Diseases (AASLD) 2011 Liver Meeting in San Francisco, USA, Boehringer Ingelheim presented findings of their Phase IIb trial, which demonstrated that the interferon-free combination of BI 201335, with their polymerase inhibitor BI 207127 (SOUND-C2) resulting in 76% of patients achieving a virological response at week 12 and 63% of patients achieved SVR12, an undetectable virus 12 weeks after treatment, at week 16.
In addition to their BI 201335 results, the company also presented their SILEN-C1 and SILEN-C3 study results at the AASLD, demonstrating that BI 201335/ PegIFN/RBV's potentially shortens the time of treatment and improves the likelihood of viral cure (SVR). These Phase IIb results provide a strong case for further development, whilst BI 201335 continues its progress through Phase III.
Written by: Grace Rattue
From Medical News Today
Boehringer Ingelheim Completes Patient Entry For Phase III Trial Program In Hepatitis C
12 Dec 2011
According to Boehringer Ingelheim's announcement, the company's large-scale Phase III clinical trial program for BI210335, an investigational, oral protease inhibitor for the treatment of chronic hepatitis C virus (HCV) has randomized the final patient for treatment.
Their current extensive trial program is conducted in 15 countries, with key regions in the E.U., Japan, the U.S., Canada, Korea, Taiwan and Russia at over 350 sites and involves almost 2,000 treatment-experienced and treatment-naïve patients overall.
The program's three Phase III trials will be carried out to assess BI 201335 combined with the golden standard treatment of pegylated interferon (pegIFN) and ribavirin (RBV) in patients with chronic genotype-1 HCV. The majority of HCV patients infected with the genotype 1 virus are amongst the most difficult patient groups to treat. The study program's primary clinical endpoint is the assessment of "sustained viral response" (SVR), considered to be a viral cure, with results from the Phase III trials expected in the first half of 2013.
The complete BI 201335 program was awarded a Fast Track designation by the FDA. The U.S. Food and Drug Administration has designed the Fast Track process to enable the development and review process of important new drugs to treat serious diseases more rapidly than usual to fill an unmet medical need.
Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim said: "We are progressing our BI 201335 program with a high priority to leverage its potential to improve cure rates in HCV treatment. We believe our HCV-pipeline may become an important tool to fight a chronic disease that affects over 170 million people worldwide."
Last month at the American Association for the Study of Liver Diseases (AASLD) 2011 Liver Meeting in San Francisco, USA, Boehringer Ingelheim presented findings of their Phase IIb trial, which demonstrated that the interferon-free combination of BI 201335, with their polymerase inhibitor BI 207127 (SOUND-C2) resulting in 76% of patients achieving a virological response at week 12 and 63% of patients achieved SVR12, an undetectable virus 12 weeks after treatment, at week 16.
In addition to their BI 201335 results, the company also presented their SILEN-C1 and SILEN-C3 study results at the AASLD, demonstrating that BI 201335/ PegIFN/RBV's potentially shortens the time of treatment and improves the likelihood of viral cure (SVR). These Phase IIb results provide a strong case for further development, whilst BI 201335 continues its progress through Phase III.
Written by: Grace Rattue
Tuesday, November 15, 2011
Medivir updates investors on Hepatitis C programs...
Medivir offers an update on it's HCV development projects including the phase IIb trials for it's once daily. HCV protease inhibitor TMC435 and the early development programs for it's HCV nucleoside and a nucleotide inhibitors. For TMC435: results from the PILLAR trial looking at TMC435 + P/R in treatment naive genotype 1 subjects found 81-86% of patients achieved SVR24, compared to 65% in the placebo + P/R arm. A majority of patients (86%) in the TMC435 treatment arms had a shortened treatment duration of treatment (24 weeks), compared to a 48 weeks in the placebo + P/R arm. For the ASPIRE trial, looking at TMC435 + P/R in partial and null responders to previous treatment. The TMC435 subgroups achieved substantially higher viral cure rates (SVR24) compared to the control group (PegIFN and RBV alone): 85% vs. 37% in prior relapsers, 75% vs. 9% in prior partial responders and 51% vs. 19% in prior null responders. Other interesting notes include a change in primary endpoint from SVR24 to SVR12 in the TMC435 Phase III trials; a Phase III TMC435 + P/R vs Telaprevir + P/R in nonresponders yet to be started; an interferon-free, combination trial looking at TMC435 + Pharmasset's PSI-7977 with and without ribavirin in genotype 1 non-responders. We're likely to see more companies pair combinations of drugs as the 2nd and 3rd generation DAAs move forward in development and others are abandoned due to inferior efficacy and/or side effect issues.
Medivir: Key News from the Ongoing Capital Markets Day
HUDDINGE, Sweden, Nov 15, 2011 (BUSINESS WIRE) -- Regulatory News:
Medivir AB, a research-based speciality pharmaceutical company focused on infectious diseases, reports the following key news concerning their hepatitis C projects.
Medivir programmes in collaboration with Tibotec Pharmaceuticals Medivir and Tibotec Pharmaceuticals have two programmes for the development of antiviral therapies for future treatment of hepatitis C (HCV), these are based on the HCV protease and polymerase drug targets.
In the protease project, TMC435 is in global phase III development in both treatment naive and in patients that have relapsed after previous treatment with pegylated interferon (PegIFN) and ribavirin (RBV) in patients with chronic hepatitis C genotype 1.
The HCV polymerase collaboration program consists of two early development projects, a nucleoside and a nucleotide inhibitor.
TMC435 (NS3/4A protease inhibitor) presently in development in Hepatitis C genotype 1 infected patients.
Phase IIb studies Final SVR24 data from the phase IIb study PILLAR, in treatment-naive patients, was presented last week at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, CA, USA. Results from this final PILLAR analysis showed that TMC435 administered in combination with peginterferon a-2a and ribavirin (PR) resulted in significantly higher sustained virologic response (SVR) rates compared to placebo plus PR, with the majority of TMC435 patients able to shorten total treatment duration to 24 weeks based on response-guided therapy.
-- In the 150 mg TMC435 treatment groups, 81-86 percent of patients achieved SVR24, compared to 65 percent of patients treated in the placebo arm. In addition, 86 percent of patients in the TMC435 treatment arms had a shortened treatment duration of 24 weeks, compared to a 48 weeks treatment duration for patients who received placebo plus P/R.
-- The once daily dosed TMC435 was generally safe and well tolerated at all doses and treatment durations.
Medivir recently issued a press release on final results from phase IIb study ASPIRE This trial evaluated TMC435 once daily in addition to pegylated interferon (PegIFN) and ribavirin (RBV) in patients with chronic hepatitis C whose prior treatment with PegIFN and RBV was unsuccessful either because they relapsed, had a partial response or had a null response.
-- Data from the ASPIRE study showed that patients in each of these subgroups who were treated with TMC435-based combination therapy achieved superior rates of sustained virologic response (viral cure) compared to those retreated with pegylated-interferon and ribavirin alone.
-- All TMC435 subgroups achieved substantially higher viral cure rates (SVR24) compared to control group (PegIFN and RBV alone): 85% vs. 37% in prior relapsers, 75% vs. 9% in prior partial responders and 51% vs. 19% in prior null responders.
-- The once daily TMC435 was generally safe and well tolerated at all doses and treatment durations. Phase III studies
SVR12 - new endpoint
-- In the ongoing phase III studies in naive and patients that have relapsed following previous treatment, the primary endpoint has been changed from SVR24 to SVR12 following recent discussions with the FDA. These studies (QUEST 1 &2 and PROMISE) were all fully recruited in August.
Phase III study in non-responder patients to be initiated
-- Phase III study in prior partial and null responder HCV genotype 1 patients will start within six months. This study will evaluate efficacy, safety and tolerability for TMC435 vs telaprevir in combination with PegINFa-2a and Ribavirin in chronic Hepatitis C patients.
Phase II interferon free combination study with TMC435 and PSI-7977
-- This interferon free phase II combination study will commence shortly. It will evaluate TMC435 and PSI-7977 in combination with and without ribavirin for 12 and 24 weeks in genotype 1 patients who had a prior null response to Peg-IFN/RBV. The study design is now posted on www.clinicaltrials.gov .
HCV polymerase collaboration
TMC649128 TMC649128, the first NS5B nucleoside polymerase inhibitor under the collaboration, entered into clinical development in Q1-2011. It was safe and well tolerated at all doses tested for up to 14 days. However the antiviral activity failed to meet the target product profile and therefore the clinical development has now been discontinued.
Nucleotide program The focus of HCV polymerase collaboration is now on a liver targeted nucleotide polymerase inhibitor program. A clinical candidate has been selected and the project is now in preclinical development stage.
Capital Markets Day Presentation The presentation from this research & development update is available on our website under the heading Investor Relations / Latest Events.
For more information about Medivir, please visit the Company's website: www.medivir.com .
This information was brought to you by Cision http://www.cisionwire.com
SOURCE: Medivir
Medivir: Key News from the Ongoing Capital Markets Day
HUDDINGE, Sweden, Nov 15, 2011 (BUSINESS WIRE) -- Regulatory News:
Medivir AB, a research-based speciality pharmaceutical company focused on infectious diseases, reports the following key news concerning their hepatitis C projects.
Medivir programmes in collaboration with Tibotec Pharmaceuticals Medivir and Tibotec Pharmaceuticals have two programmes for the development of antiviral therapies for future treatment of hepatitis C (HCV), these are based on the HCV protease and polymerase drug targets.
In the protease project, TMC435 is in global phase III development in both treatment naive and in patients that have relapsed after previous treatment with pegylated interferon (PegIFN) and ribavirin (RBV) in patients with chronic hepatitis C genotype 1.
The HCV polymerase collaboration program consists of two early development projects, a nucleoside and a nucleotide inhibitor.
TMC435 (NS3/4A protease inhibitor) presently in development in Hepatitis C genotype 1 infected patients.
Phase IIb studies Final SVR24 data from the phase IIb study PILLAR, in treatment-naive patients, was presented last week at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, CA, USA. Results from this final PILLAR analysis showed that TMC435 administered in combination with peginterferon a-2a and ribavirin (PR) resulted in significantly higher sustained virologic response (SVR) rates compared to placebo plus PR, with the majority of TMC435 patients able to shorten total treatment duration to 24 weeks based on response-guided therapy.
-- In the 150 mg TMC435 treatment groups, 81-86 percent of patients achieved SVR24, compared to 65 percent of patients treated in the placebo arm. In addition, 86 percent of patients in the TMC435 treatment arms had a shortened treatment duration of 24 weeks, compared to a 48 weeks treatment duration for patients who received placebo plus P/R.
-- The once daily dosed TMC435 was generally safe and well tolerated at all doses and treatment durations.
Medivir recently issued a press release on final results from phase IIb study ASPIRE This trial evaluated TMC435 once daily in addition to pegylated interferon (PegIFN) and ribavirin (RBV) in patients with chronic hepatitis C whose prior treatment with PegIFN and RBV was unsuccessful either because they relapsed, had a partial response or had a null response.
-- Data from the ASPIRE study showed that patients in each of these subgroups who were treated with TMC435-based combination therapy achieved superior rates of sustained virologic response (viral cure) compared to those retreated with pegylated-interferon and ribavirin alone.
-- All TMC435 subgroups achieved substantially higher viral cure rates (SVR24) compared to control group (PegIFN and RBV alone): 85% vs. 37% in prior relapsers, 75% vs. 9% in prior partial responders and 51% vs. 19% in prior null responders.
-- The once daily TMC435 was generally safe and well tolerated at all doses and treatment durations. Phase III studies
SVR12 - new endpoint
-- In the ongoing phase III studies in naive and patients that have relapsed following previous treatment, the primary endpoint has been changed from SVR24 to SVR12 following recent discussions with the FDA. These studies (QUEST 1 &2 and PROMISE) were all fully recruited in August.
Phase III study in non-responder patients to be initiated
-- Phase III study in prior partial and null responder HCV genotype 1 patients will start within six months. This study will evaluate efficacy, safety and tolerability for TMC435 vs telaprevir in combination with PegINFa-2a and Ribavirin in chronic Hepatitis C patients.
Phase II interferon free combination study with TMC435 and PSI-7977
-- This interferon free phase II combination study will commence shortly. It will evaluate TMC435 and PSI-7977 in combination with and without ribavirin for 12 and 24 weeks in genotype 1 patients who had a prior null response to Peg-IFN/RBV. The study design is now posted on www.clinicaltrials.gov .
HCV polymerase collaboration
TMC649128 TMC649128, the first NS5B nucleoside polymerase inhibitor under the collaboration, entered into clinical development in Q1-2011. It was safe and well tolerated at all doses tested for up to 14 days. However the antiviral activity failed to meet the target product profile and therefore the clinical development has now been discontinued.
Nucleotide program The focus of HCV polymerase collaboration is now on a liver targeted nucleotide polymerase inhibitor program. A clinical candidate has been selected and the project is now in preclinical development stage.
Capital Markets Day Presentation The presentation from this research & development update is available on our website under the heading Investor Relations / Latest Events.
For more information about Medivir, please visit the Company's website: www.medivir.com .
This information was brought to you by Cision http://www.cisionwire.com
SOURCE: Medivir
Thursday, July 7, 2011
Medivir/Tibotec's HCV protease inhibitor TMC435 receives FDA 'Fast-Track' status...
Medivir: TMC435 has Received Fast Track Designation from the FDA and TMC435 will be studied in combination with Pharmasset's PSI-7977 for HCV genotype-1
HUDDINGE, Sweden, Jul 06, 2011 (BUSINESS WIRE) -- Regulatory News:
Medivir AB (sto:MVIRB)(omx:MVIR), is an emerging research-based specialty pharmaceutical company focused on infectious diseases.
Medivir today announced that its investigational protease inhibitor TMC435 has received "Fast Track" designation by the U.S. Food and Drug Administration ("FDA") for the treatment of chronic hepatitis C (CHC) genotype-1 infection. This is based on TMC435's potential to address unmet medical needs in the treatment of CHC infection compared to currently approved therapies.
TMC435 may offer:
-- High sustained virological response (SVR) rates in genotype-1 HCV-infected patients, including hard-to-treat subgroups
-- Short treatment duration
-- Favorable overall safety and tolerability profile
-- A convenient once-daily (q.d.) dosing regimen
Furthermore, Medivir also confirms the intention to start a proof-of-concept oral, interferon-free phase 2 trial, investigating the combination of TMC435, a once daily NS3/4A protease inhibitor (PI) for the treatment of genotype-1 chronic hepatitis C virus (HCV) infection and Pharmasset's PSI-7977, a once daily nucleotide NS5B polymerase inhibitor. The phase 2 study, which is being managed by Tibotec Pharmaceuticals, will investigate the efficacy and safety of 12 weeks or 24 weeks of TMC435 150 mg q.d. in combination with PSI-7977 400 mg q.d. with or without ribavirin in prior null responders to peginterferon/ribavirin therapy. The primary endpoint of the trial will be sustained virological response at 12 weeks (SVR12).
Bertil Samuelsson, CSO, of Medivir commented, "We are delighted to have received the Fast Track designation for TMC435 from the FDA. This shows that TMC435 with its high safety profile, efficacy, short treatment duration and convenience of once daily dosing is believed to have the potential to provide benefit over current treatments. We believe TMC435 has the potential to become a cornerstone of future direct-acting antiviral combinations for HCV therapy. We are thus very pleased over the clinical collaboration agreement Pharmasset announced today with Tibotec, and the coming start-up of a TMC435 combination trial with Pharmasset's once daily NS5B nucleotide inhibitor PSI-7977. This is one of several ongoing TMC435 combination trials and we expect the momentum to continue with regards to the development of TMC435"
About Fast Track
Fast Track is a process designed to facilitate the development, and expedite the review of drugs to treat serious diseases and to fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious diseases. "Filling an unmet medical need" is defined as providing a therapy where none exists or providing a therapy that may potentially be superior to existing therapy. If there are existing therapies, a fast track drug must show some advantage over available treatment, such as:
-- Showing superior effectiveness
-- Avoiding serious side effects of an available treatment
-- Improving the diagnosis of a serious disease where early diagnosis results in an improved outcome
-- Decreasing a clinically significant toxicity of an accepted treatment
A drug that receives Fast Track designation is eligible for some or all of the following:
-- More frequent meetings with the FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval
-- More frequent written correspondence from the FDA about such things as the design of the proposed clinical trials
-- Eligibility for Accelerated Approval, i.e., approval on an effect on a surrogate or substitute endpoint reasonably likely to predict clinical benefit
-- Rolling Review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by FDA, rather than waiting until every section of the application is completed before the entire application can be reviewed. NDA review usually does not begin until the drug company has submitted the entire application to the FDA
-- Dispute resolution if the drug company is not satisfied with an FDA decision not to grant Fast Track status.
In addition, most drugs that are eligible for Fast Track designation are likely to be considered appropriate to receive a Priority Review.
Once a drug receives Fast Track designation, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.
About TMC435
TMC435, an investigational CHC protease inhibitor currently in phase 3 clinical development, is a highly potent, selective and safe once-daily (q.d.) drug jointly developed by Tibotec Pharmaceuticals to treat chronic hepatitis C virus infections.
TMC435 is being developed in combination with PegIFN/RBV and in combination with Direct-acting Antiviral (DAA) agents without peginterferon and with or without ribavirin (RBV). In June 2011 the combination study of TMC435 with TMC647055, a non-nucleoside NS5B polymerase inhibitor being developed by Tibotec Pharmaceuticals, was initiated.
Three global clinical phase 3 response guided studies were initiated in early 2011 by Tibotec:
-- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
-- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
-- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
Phase 3 programs for TMC435 are also ongoing in Japan.
In parallel with the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
For additional information from these studies, please see www.medivir.com and www.clinicaltrials.gov
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The US Centers for Disease Control ("CDC") has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a novel protease inhibitor is in phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals. In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia to ensure timely commercialization of TMC435 in the Nordic markets, once approved.
Medivir's first product, the unique cold sore product Xerese(TM)/Xerclear(R) was launched on the US market in February 2011. Xerese(TM)/Xerclear(R), which has been approved in both the US and Europe is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia. Rights in North America, Canada and Mexico have recently been sold to Meda AB. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: www.medivir.com .
This information was brought to you by Cision http://www.cisionwire.com
SOURCE: Medivir
HUDDINGE, Sweden, Jul 06, 2011 (BUSINESS WIRE) -- Regulatory News:
Medivir AB (sto:MVIRB)(omx:MVIR), is an emerging research-based specialty pharmaceutical company focused on infectious diseases.
Medivir today announced that its investigational protease inhibitor TMC435 has received "Fast Track" designation by the U.S. Food and Drug Administration ("FDA") for the treatment of chronic hepatitis C (CHC) genotype-1 infection. This is based on TMC435's potential to address unmet medical needs in the treatment of CHC infection compared to currently approved therapies.
TMC435 may offer:
-- High sustained virological response (SVR) rates in genotype-1 HCV-infected patients, including hard-to-treat subgroups
-- Short treatment duration
-- Favorable overall safety and tolerability profile
-- A convenient once-daily (q.d.) dosing regimen
Furthermore, Medivir also confirms the intention to start a proof-of-concept oral, interferon-free phase 2 trial, investigating the combination of TMC435, a once daily NS3/4A protease inhibitor (PI) for the treatment of genotype-1 chronic hepatitis C virus (HCV) infection and Pharmasset's PSI-7977, a once daily nucleotide NS5B polymerase inhibitor. The phase 2 study, which is being managed by Tibotec Pharmaceuticals, will investigate the efficacy and safety of 12 weeks or 24 weeks of TMC435 150 mg q.d. in combination with PSI-7977 400 mg q.d. with or without ribavirin in prior null responders to peginterferon/ribavirin therapy. The primary endpoint of the trial will be sustained virological response at 12 weeks (SVR12).
Bertil Samuelsson, CSO, of Medivir commented, "We are delighted to have received the Fast Track designation for TMC435 from the FDA. This shows that TMC435 with its high safety profile, efficacy, short treatment duration and convenience of once daily dosing is believed to have the potential to provide benefit over current treatments. We believe TMC435 has the potential to become a cornerstone of future direct-acting antiviral combinations for HCV therapy. We are thus very pleased over the clinical collaboration agreement Pharmasset announced today with Tibotec, and the coming start-up of a TMC435 combination trial with Pharmasset's once daily NS5B nucleotide inhibitor PSI-7977. This is one of several ongoing TMC435 combination trials and we expect the momentum to continue with regards to the development of TMC435"
About Fast Track
Fast Track is a process designed to facilitate the development, and expedite the review of drugs to treat serious diseases and to fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious diseases. "Filling an unmet medical need" is defined as providing a therapy where none exists or providing a therapy that may potentially be superior to existing therapy. If there are existing therapies, a fast track drug must show some advantage over available treatment, such as:
-- Showing superior effectiveness
-- Avoiding serious side effects of an available treatment
-- Improving the diagnosis of a serious disease where early diagnosis results in an improved outcome
-- Decreasing a clinically significant toxicity of an accepted treatment
A drug that receives Fast Track designation is eligible for some or all of the following:
-- More frequent meetings with the FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval
-- More frequent written correspondence from the FDA about such things as the design of the proposed clinical trials
-- Eligibility for Accelerated Approval, i.e., approval on an effect on a surrogate or substitute endpoint reasonably likely to predict clinical benefit
-- Rolling Review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by FDA, rather than waiting until every section of the application is completed before the entire application can be reviewed. NDA review usually does not begin until the drug company has submitted the entire application to the FDA
-- Dispute resolution if the drug company is not satisfied with an FDA decision not to grant Fast Track status.
In addition, most drugs that are eligible for Fast Track designation are likely to be considered appropriate to receive a Priority Review.
Once a drug receives Fast Track designation, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.
About TMC435
TMC435, an investigational CHC protease inhibitor currently in phase 3 clinical development, is a highly potent, selective and safe once-daily (q.d.) drug jointly developed by Tibotec Pharmaceuticals to treat chronic hepatitis C virus infections.
TMC435 is being developed in combination with PegIFN/RBV and in combination with Direct-acting Antiviral (DAA) agents without peginterferon and with or without ribavirin (RBV). In June 2011 the combination study of TMC435 with TMC647055, a non-nucleoside NS5B polymerase inhibitor being developed by Tibotec Pharmaceuticals, was initiated.
Three global clinical phase 3 response guided studies were initiated in early 2011 by Tibotec:
-- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
-- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
-- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
Phase 3 programs for TMC435 are also ongoing in Japan.
In parallel with the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
For additional information from these studies, please see www.medivir.com and www.clinicaltrials.gov
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The US Centers for Disease Control ("CDC") has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a novel protease inhibitor is in phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals. In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia to ensure timely commercialization of TMC435 in the Nordic markets, once approved.
Medivir's first product, the unique cold sore product Xerese(TM)/Xerclear(R) was launched on the US market in February 2011. Xerese(TM)/Xerclear(R), which has been approved in both the US and Europe is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia. Rights in North America, Canada and Mexico have recently been sold to Meda AB. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: www.medivir.com .
This information was brought to you by Cision http://www.cisionwire.com
SOURCE: Medivir
Thursday, May 26, 2011
Achillion Pharmaceuticals ACH-2684 HCV Pan-Genotype HCV Protease inhibitors goes into the clinic...
Achillion Pharmaceuticals announces first-in-human trials of it's own ACH-2684 HCV protease inhibitor. This is a phase 1 trial designed to study the safety, tolerability, pharmacokinetic profile and antiviral activity of the drug in up to 78 healthy volunteers and up to 40 HCV-infected, genotype 1 & 3 patients. ACH-2684 is said to be active against all six genotypes and offers once-daily dosing
First-in-Human Trial Will Evaluate Safety of Pan-Genotypic Protease Inhibitor in Both Healthy Subjects and Genotype 1 or 3 HCV-Infected Patients
NEW HAVEN, Conn., May 25, 2011 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN), a leader in the discovery and development of small molecule drugs to combat the most challenging infectious diseases, today announced that the Company has begun dosing in a Phase 1 clinical trial of ACH-2684, a novel pan-genotypic protease inhibitor being developed for the treatment of chronic hepatitis C virus (HCV) infection.
The Phase 1 clinical study is a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity of ACH-2684. The trial consists of three segments including assessment of single ascending oral doses in healthy volunteers, a 14 day multiple ascending doses segment in healthy volunteers, and evaluation of 3 days of oral ascending repeat doses in subjects with either genotype 1 or genotype 3 hepatitis C infection. The trial will take place in the United States and is designed to enroll up to 78 healthy volunteers and up to 40 HCV-infected patients.
"This first-in-human clinical trial will be instrumental in establishing the safety profile of ACH-2684 in humans," stated Elizabeth A. Olek, D.O., Vice President and Chief Medical Officer of Achillion. "It will also provide Achillion with important preliminary efficacy data against HCV genotypes 1 and 3, and help us to select doses for subsequent clinical development."
"We are very excited to take ACH-2684 into the clinic and advance what we hope will be a unique pan-genotypic, once-daily protease inhibitor," said Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "Furthermore, we expect to shortly launch the 12-week segment of the Phase 2 trial of our lead ACH-1625 protease inhibitor, as well as a Phase 1 trial of our ACH-2928 NS5A inhibitor. We believe we remain poised to deliver a trio of important HCV clinical milestones near the end of this year, namely, 12-week EVR results on ACH-1625 and human proof-of-concept data on both ACH-2684 and ACH-2928. These are all important components in our ultimate strategy of becoming a leader in the development of HCV combination therapies involving our protease and NS5A inhibitors."
About ACH-2684
ACH-2684 is a pan-genotypic HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-2684 is a macro-cyclic, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-2684 demonstrated pico-molar potency, excellent pharmacokinetic properties and safety profile at high drug exposures. ACH-2684 also exhibits rapid and extensive partitioning to the liver, as well as high liver/plasma ratios in preclinical studies. ACH-2684 has shown pico-molar potency against NS3 protease that is specific to HCV. It is active against the 6 known genotypes of HCV and exhibits equipotent activity against HCV genotypes 1a and 1b at an IC50 of approximately 100 picomolar. The drug candidate was discovered internally and is being advanced by Achillion.
About HCV
The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide and The American Association of Liver Disease estimates that up to 80% of individuals become chronically infected following exposure to the virus. If left untreated, chronic hepatitis can lead to permanent liver damage, which can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.
About Achillion Pharmaceuticals
Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including hepatitis C and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.
Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including statements with respect to the potency, safety and other characteristics of ACH-2684, which may not be duplicated in clinical studies and Achillion's expectations regarding timing and duration of clinical trials and reporting of results from clinical trials of ACH-1625, ACH-2684 and ACH-2928. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are: uncertainties relating to results of clinical trials, unexpected regulatory actions or delays, and Achillion's ability to obtain additional funding required to conduct its research, development and commercialization activities. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2010.
All forward-looking statements reflect Achillion's expectations only as of the date of this release and should not be relied upon as reflecting Achillion's views, expectations or beliefs at any date subsequent to the date of this release. Achillion anticipates that subsequent events and developments may cause these views, expectations and beliefs to change. However, while Achillion may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so.
CONTACT: Company Contact:
Glenn Schulman
Achillion Pharmaceuticals, Inc.
Tel. (203) 752-5510
gschulman@achillion.com
Investors:
Mary Kay Fenton
Achillion Pharmaceuticals, Inc.
Tel. (203) 624-7000
mfenton@achillion.com
Media:
Christin Culotta Miller
Ogilvy PR
Tel. (646) 229-5178
christin.miller@ogilvypr.com
First-in-Human Trial Will Evaluate Safety of Pan-Genotypic Protease Inhibitor in Both Healthy Subjects and Genotype 1 or 3 HCV-Infected Patients
NEW HAVEN, Conn., May 25, 2011 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN), a leader in the discovery and development of small molecule drugs to combat the most challenging infectious diseases, today announced that the Company has begun dosing in a Phase 1 clinical trial of ACH-2684, a novel pan-genotypic protease inhibitor being developed for the treatment of chronic hepatitis C virus (HCV) infection.
The Phase 1 clinical study is a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity of ACH-2684. The trial consists of three segments including assessment of single ascending oral doses in healthy volunteers, a 14 day multiple ascending doses segment in healthy volunteers, and evaluation of 3 days of oral ascending repeat doses in subjects with either genotype 1 or genotype 3 hepatitis C infection. The trial will take place in the United States and is designed to enroll up to 78 healthy volunteers and up to 40 HCV-infected patients.
"This first-in-human clinical trial will be instrumental in establishing the safety profile of ACH-2684 in humans," stated Elizabeth A. Olek, D.O., Vice President and Chief Medical Officer of Achillion. "It will also provide Achillion with important preliminary efficacy data against HCV genotypes 1 and 3, and help us to select doses for subsequent clinical development."
"We are very excited to take ACH-2684 into the clinic and advance what we hope will be a unique pan-genotypic, once-daily protease inhibitor," said Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "Furthermore, we expect to shortly launch the 12-week segment of the Phase 2 trial of our lead ACH-1625 protease inhibitor, as well as a Phase 1 trial of our ACH-2928 NS5A inhibitor. We believe we remain poised to deliver a trio of important HCV clinical milestones near the end of this year, namely, 12-week EVR results on ACH-1625 and human proof-of-concept data on both ACH-2684 and ACH-2928. These are all important components in our ultimate strategy of becoming a leader in the development of HCV combination therapies involving our protease and NS5A inhibitors."
About ACH-2684
ACH-2684 is a pan-genotypic HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-2684 is a macro-cyclic, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-2684 demonstrated pico-molar potency, excellent pharmacokinetic properties and safety profile at high drug exposures. ACH-2684 also exhibits rapid and extensive partitioning to the liver, as well as high liver/plasma ratios in preclinical studies. ACH-2684 has shown pico-molar potency against NS3 protease that is specific to HCV. It is active against the 6 known genotypes of HCV and exhibits equipotent activity against HCV genotypes 1a and 1b at an IC50 of approximately 100 picomolar. The drug candidate was discovered internally and is being advanced by Achillion.
About HCV
The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide and The American Association of Liver Disease estimates that up to 80% of individuals become chronically infected following exposure to the virus. If left untreated, chronic hepatitis can lead to permanent liver damage, which can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.
About Achillion Pharmaceuticals
Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including hepatitis C and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.
Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including statements with respect to the potency, safety and other characteristics of ACH-2684, which may not be duplicated in clinical studies and Achillion's expectations regarding timing and duration of clinical trials and reporting of results from clinical trials of ACH-1625, ACH-2684 and ACH-2928. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are: uncertainties relating to results of clinical trials, unexpected regulatory actions or delays, and Achillion's ability to obtain additional funding required to conduct its research, development and commercialization activities. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2010.
All forward-looking statements reflect Achillion's expectations only as of the date of this release and should not be relied upon as reflecting Achillion's views, expectations or beliefs at any date subsequent to the date of this release. Achillion anticipates that subsequent events and developments may cause these views, expectations and beliefs to change. However, while Achillion may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so.
CONTACT: Company Contact:
Glenn Schulman
Achillion Pharmaceuticals, Inc.
Tel. (203) 752-5510
gschulman@achillion.com
Investors:
Mary Kay Fenton
Achillion Pharmaceuticals, Inc.
Tel. (203) 624-7000
mfenton@achillion.com
Media:
Christin Culotta Miller
Ogilvy PR
Tel. (646) 229-5178
christin.miller@ogilvypr.com
Friday, May 20, 2011
Medivir Announces Positive 48-week Interim Data from TMC435 Hepatitis C Phase 2b ASPIRE Study in Treatment-Experienced Genotype-1 Patients...
I need to add 'SVR4' to my list of HCV Direct Acting Antiviral terminology... 'SVR4' is SVR 4 weeks post end of treatment date. Glad to get that squared away. This press release covers the majority of results of the phase IIb trial (ASPIRE) with the HCV protease inhibitor TMC435 looking at those who were previous non-responders to previous Peg-inf + P/R therapy - Relapsers, Partial Responders and Null-Responders to be specific. SVR4 in the TMC435 150mg + P/R was achieved in 88%, 77% and 57% oof those respective populations vs 50%, 11% and 23% in the placebo + P/R ar, again, respectively. No relevant differences between the 12, 24 and 48 week arms. Serious AEs were reported in 6.1% subjects in the placebo and vs 8.3% of the subjects treated with TMC435 with no substantial differences seen between the TMC435 dose groups. AEs leading to treatment discontinuation were reported in 4.5% of the placebo subjects and in 8.8% of the TMC435 treated subjects. The relative lack of AE's compared to the first generation of HCV PIs and the once a day dosing make TMC435 one to keep our eyes on.
HUDDINGE, Sweden, May 20, 2011 /PRNewswire/ --
- All TMC435 Patient Subgroups Achieved Substantially Higher SVR4 Rates (Undetectable Virus 4 Weeks After End of Treatment) Compared to pegylated-interferon and ribavirin Alone
- TMC435 was Safe and Well Tolerated at All Doses and Treatment Durations
Medivir AB (OMX: MVIR), the emerging research-based specialty
pharmaceutical company focused on infectious diseases, today announced results from the ASPIRE phase 2b study that evaluates the addition of once daily TMC435 to pegylated interferon and ribavirin in patients with genotype 1 chronic hepatitis C whose prior treatment with pegylated-interferon (PegIFN) and ribavirin (RBV) was unsuccessful either because they relapsed, had a partial response or had a null response.
Bertil Samuelsson, CSO of Medivir, commented, "We are delighted with the encouraging efficacy and safety results shown by TMC435-based triple therapy over pegylated-interferon and ribavirin, in this 48-Week interim analysis of the ASPIRE study in treatment experienced genotype-1 hepatitis C patients. This patient group is known to be the most difficult one to treat, where in particular prior null and partial responder groups respond very poorly upon retreatment with PegIFN/RBV alone. With several global phase 3 clinical trials ongoing in hepatitis C patients we are expecting the momentum to continue with regards to the development of TMC435."
ASPIRE (C206) - Design and Week-48 Interim Analysis
TMC435, a potent, once-daily, oral hepatitis C virus protease inhibitor is being developed by Tibotec jointly with Medivir. The randomized, placebo-controlled, double-blind ASPIRE study evaluates the effect of TMC435 in combination with pegylated-interferon and ribavirin in 462 patients infected with genotype-1 hepatitis C virus who have failed prior treatment with PegIFN/RBV. The study includes patients that have relapsed, achieved partial response, or achieved no response (null responders) to SoC treatment and where 62 percent (287/462) of patients overall had advanced liver disease, periportal or septal fibrosis or cirrhosis (scarring of the liver) upon study entry (Metavir score F2-F4).
Patients were equally randomized to 1 of 7 different treatment arms: 6 TMC435 treatment arms and one placebo arm. TMC435 was administered once daily at a dose of either 100 mg or 150 mg given for either 12, 24, or 48 weeks in combination with PegIFN/RBV. PegIFN/RBV treatment was continued in all patients until the study completion at week 48. This interim analysis was performed when all patients had completed 48 weeks of treatment or discontinued earlier. The analysis was done based on the intent-to-treat, ITT, population which included all randomized subjects who took at least one dose of the study medication. SVR4, Sustained Virologic Response 4 weeks after planned end of treatment data, was available for 94% and 84% of TMC435 and placebo patients respectively.
ASPIRE Results - Efficacy
In this Week 48 interim analysis, all subgroups of treatment-experienced patients who failed previous peginterferon and ribavirin treatment, achieved substantially higher virologic response rates following treatment with TMC435-containing regimen at all doses and durations, compared with pegylated-interferon and ribavirin.
There was no relevant difference in virological response between the TMC435 150 mg dose groups who received TMC435-based triple therapy of 12 weeks, 24 weeks or 48 weeks. At end of treatment (EoT) 92%, 83% and 71% of relapser patients, partial responder patients and null responder patients taking TMC435 150 mg once daily and placebo, respectively, achieved undetectable HCV RNA levels compared to 70%, 17% and 25% in the placebo PegIFN/RBV groups respectively. At week 4 after cessation of treatment (SVR4) 88%, 77% and 57% of prior relapser patients, partial responder patients and null responder patients taking TMC435 150 mg once daily and placebo, respectively, achieved undetectable HCV RNA levels, compared to 50%, 11% and 23% in the placebo groups, respectively.
Virological Response Rates in TMC435 Dose Groups (150 mg q.d.) vs
Placebo
TMC435 TMC435 TMC435 All TMC435 Placebo
% (n/N) 12PR48 24PR48 48PR48 PR48 PR48
N=66 N=68 N=65 N=199 N=66
Prior EoT 92 (24/26) 93 (25/27) 92 (24/26) 92 (73/79) 70 (19/27)
Relapser
SVR4 84 (21/25) 93 (25/27) 85 (22/26) 87 (68/78) 50 (12/24)
Prior EoT 78 (18/23) 83 (20/24) 86 (19/22) 83 (57/69) 17 (4/23)
Partial
Responder SVR4 64 (14/22) 86 (18/21) 82 (18/22) 77 (50/65) 11 (2/18)
Prior Null EoT 65 (11/17) 71 (12/17) 77 (13/17) 71 (36/51) 25 (4/16)
Responder
SVR4 56 (9/16) 60 (9/15) 56 (9/16) 57 (27/47) 23 (3/13)
q.d.: once daily; PR: pegIFNalpha-2A and ribavirin; EoT: End of Treatment,
SVR4: patients with undetectable HCV RNA (<25 IU/mL Undetectable) at EOT and 4 weeks after planned EoT. Prior Relapser: undetectable HCV RNA at EoT and detectable within 24 weeks of follow-up
Partial Responders: more than 2 log reduction in HCV RNA at W12 but not achieving undetectable at EoT
Prior Null Responders: less than 2 log reduction in HCV RNA at W12
Results - Safety and Tolerability
TMC435 was generally safe and well tolerated and overall incidence of adverse events (AEs) was similar across treatment groups. Most of the AEs were grade 1 or 2 in severity. Serious AEs (SAEs) were reported in 6.1% subjects in the placebo and in 8.3% of the subjects treated with TMC435 with no substantial differences seen between the TMC435 dose groups. AEs leading to treatment discontinuation were reported in 4.5% of the placebo subjects and in 8.8% of the TMC435 treated subjects. Patients in the TMC435 ASPIRE treatment groups had overall longer treatment duration than patients in the placebo group due to a higher frequency of early discontinuation in the placebo group caused by treatment failures (i.e. reaching viral stopping rules). The most common AEs during the treatment period were headache, fatigue, pruritus and influenza-like illness.
Incidence was similar across treatment groups and the level of AEs and frequency were consistent with prior phase 2b PILLAR study of TMC435.
In the safety analyses, special attention was given to the following AEs of interest: hepatobiliary AEs, pruritus, rash, anemia and cardiac events. Most AEs of interest were grade 1 or 2 in severity and infrequently led to treatment discontinuation. For each category of AEs of interest the incidence was similar with TMC435 and PegIFN/RBV.
Mild and reversible increases in bilirubin (total, direct and indirect) were observed in TMC435 dose groups with no differences between 100 mg and 150 mg. There were no meaningful differences between treatment groups for any of the other laboratory parameters. There were no clinically significant findings on vital signs, nor were there any relevant changes in electrocardiogram (ECG) parameters, including QTc. Mean alanine aminotransferase (ALT) levels decreased in all treatment groups.
About TMC435 in other clinical studies
TMC435 is a once-daily (q.d.) protease inhibitor drug jointly developed by Tibotec Pharmaceuticals and, to treat chronic hepatitis C virus infections.
Three global clinical phase 3 response guided studies were recently initiated by Tibotec:
- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
In parallel to the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011. Phase 3 programs for TMC435 are also ongoing in Japan.
For additional information for these studies, please see http://www.clinicaltrials.gov
Conference call for analysts and investors:
There will be a conference call today, May 20 2011, for investors and analysts at 08.00 (EDT) / 13.00 (GMT) / 14.00 (CET) to discuss the data. To dial-in to the conference call please use the following numbers:
Participant Telephone Numbers: +1-718-354-1359 USA
+46(0)8-5051-3785 Sweden
+44(0)20-7136-2053 UK
Participant code 1156834
Soundbyte Replay Access Number: +44(0)20-7111-1244 UK
+1-347-366-9565 USA
+46(0)8-5051-3897 Sweden
Replay Access Code: 1156834#
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a protease inhibitor which has recently entered phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
Medivir is also marketing its first product, the unique cold sore product Xerese(TM)/Xerclear(R) which has recently been launched on the US market. Xerese(TM)/Xerclear(R), which is also approved in Europe, is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia and with Meda AB in North America, Canada and Mexico. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: http://www.medivir.com.
For more information about Medivir, please contact:
Medivir (http://www.medivir.com):
Rein Piir, CFO & VP Investor Relations Mobile: +46-708-537-292
Bertil Samuelsson, CSO Research & Development +46-8-54683100
M:Communications:
Mary-Jane Elliott / Amber Bielecka / Katja Toon +44(0)20-7920-2330
Medivir@mcomgroup.com
USA: Roland Tomforde +1-212-232-2356
SOURCE Medivir AB
HUDDINGE, Sweden, May 20, 2011 /PRNewswire/ --
- All TMC435 Patient Subgroups Achieved Substantially Higher SVR4 Rates (Undetectable Virus 4 Weeks After End of Treatment) Compared to pegylated-interferon and ribavirin Alone
- TMC435 was Safe and Well Tolerated at All Doses and Treatment Durations
Medivir AB (OMX: MVIR), the emerging research-based specialty
pharmaceutical company focused on infectious diseases, today announced results from the ASPIRE phase 2b study that evaluates the addition of once daily TMC435 to pegylated interferon and ribavirin in patients with genotype 1 chronic hepatitis C whose prior treatment with pegylated-interferon (PegIFN) and ribavirin (RBV) was unsuccessful either because they relapsed, had a partial response or had a null response.
Bertil Samuelsson, CSO of Medivir, commented, "We are delighted with the encouraging efficacy and safety results shown by TMC435-based triple therapy over pegylated-interferon and ribavirin, in this 48-Week interim analysis of the ASPIRE study in treatment experienced genotype-1 hepatitis C patients. This patient group is known to be the most difficult one to treat, where in particular prior null and partial responder groups respond very poorly upon retreatment with PegIFN/RBV alone. With several global phase 3 clinical trials ongoing in hepatitis C patients we are expecting the momentum to continue with regards to the development of TMC435."
ASPIRE (C206) - Design and Week-48 Interim Analysis
TMC435, a potent, once-daily, oral hepatitis C virus protease inhibitor is being developed by Tibotec jointly with Medivir. The randomized, placebo-controlled, double-blind ASPIRE study evaluates the effect of TMC435 in combination with pegylated-interferon and ribavirin in 462 patients infected with genotype-1 hepatitis C virus who have failed prior treatment with PegIFN/RBV. The study includes patients that have relapsed, achieved partial response, or achieved no response (null responders) to SoC treatment and where 62 percent (287/462) of patients overall had advanced liver disease, periportal or septal fibrosis or cirrhosis (scarring of the liver) upon study entry (Metavir score F2-F4).
Patients were equally randomized to 1 of 7 different treatment arms: 6 TMC435 treatment arms and one placebo arm. TMC435 was administered once daily at a dose of either 100 mg or 150 mg given for either 12, 24, or 48 weeks in combination with PegIFN/RBV. PegIFN/RBV treatment was continued in all patients until the study completion at week 48. This interim analysis was performed when all patients had completed 48 weeks of treatment or discontinued earlier. The analysis was done based on the intent-to-treat, ITT, population which included all randomized subjects who took at least one dose of the study medication. SVR4, Sustained Virologic Response 4 weeks after planned end of treatment data, was available for 94% and 84% of TMC435 and placebo patients respectively.
ASPIRE Results - Efficacy
In this Week 48 interim analysis, all subgroups of treatment-experienced patients who failed previous peginterferon and ribavirin treatment, achieved substantially higher virologic response rates following treatment with TMC435-containing regimen at all doses and durations, compared with pegylated-interferon and ribavirin.
There was no relevant difference in virological response between the TMC435 150 mg dose groups who received TMC435-based triple therapy of 12 weeks, 24 weeks or 48 weeks. At end of treatment (EoT) 92%, 83% and 71% of relapser patients, partial responder patients and null responder patients taking TMC435 150 mg once daily and placebo, respectively, achieved undetectable HCV RNA levels compared to 70%, 17% and 25% in the placebo PegIFN/RBV groups respectively. At week 4 after cessation of treatment (SVR4) 88%, 77% and 57% of prior relapser patients, partial responder patients and null responder patients taking TMC435 150 mg once daily and placebo, respectively, achieved undetectable HCV RNA levels, compared to 50%, 11% and 23% in the placebo groups, respectively.
Virological Response Rates in TMC435 Dose Groups (150 mg q.d.) vs
Placebo
TMC435 TMC435 TMC435 All TMC435 Placebo
% (n/N) 12PR48 24PR48 48PR48 PR48 PR48
N=66 N=68 N=65 N=199 N=66
Prior EoT 92 (24/26) 93 (25/27) 92 (24/26) 92 (73/79) 70 (19/27)
Relapser
SVR4 84 (21/25) 93 (25/27) 85 (22/26) 87 (68/78) 50 (12/24)
Prior EoT 78 (18/23) 83 (20/24) 86 (19/22) 83 (57/69) 17 (4/23)
Partial
Responder SVR4 64 (14/22) 86 (18/21) 82 (18/22) 77 (50/65) 11 (2/18)
Prior Null EoT 65 (11/17) 71 (12/17) 77 (13/17) 71 (36/51) 25 (4/16)
Responder
SVR4 56 (9/16) 60 (9/15) 56 (9/16) 57 (27/47) 23 (3/13)
q.d.: once daily; PR: pegIFNalpha-2A and ribavirin; EoT: End of Treatment,
SVR4: patients with undetectable HCV RNA (<25 IU/mL Undetectable) at EOT and 4 weeks after planned EoT. Prior Relapser: undetectable HCV RNA at EoT and detectable within 24 weeks of follow-up
Partial Responders: more than 2 log reduction in HCV RNA at W12 but not achieving undetectable at EoT
Prior Null Responders: less than 2 log reduction in HCV RNA at W12
Results - Safety and Tolerability
TMC435 was generally safe and well tolerated and overall incidence of adverse events (AEs) was similar across treatment groups. Most of the AEs were grade 1 or 2 in severity. Serious AEs (SAEs) were reported in 6.1% subjects in the placebo and in 8.3% of the subjects treated with TMC435 with no substantial differences seen between the TMC435 dose groups. AEs leading to treatment discontinuation were reported in 4.5% of the placebo subjects and in 8.8% of the TMC435 treated subjects. Patients in the TMC435 ASPIRE treatment groups had overall longer treatment duration than patients in the placebo group due to a higher frequency of early discontinuation in the placebo group caused by treatment failures (i.e. reaching viral stopping rules). The most common AEs during the treatment period were headache, fatigue, pruritus and influenza-like illness.
Incidence was similar across treatment groups and the level of AEs and frequency were consistent with prior phase 2b PILLAR study of TMC435.
In the safety analyses, special attention was given to the following AEs of interest: hepatobiliary AEs, pruritus, rash, anemia and cardiac events. Most AEs of interest were grade 1 or 2 in severity and infrequently led to treatment discontinuation. For each category of AEs of interest the incidence was similar with TMC435 and PegIFN/RBV.
Mild and reversible increases in bilirubin (total, direct and indirect) were observed in TMC435 dose groups with no differences between 100 mg and 150 mg. There were no meaningful differences between treatment groups for any of the other laboratory parameters. There were no clinically significant findings on vital signs, nor were there any relevant changes in electrocardiogram (ECG) parameters, including QTc. Mean alanine aminotransferase (ALT) levels decreased in all treatment groups.
About TMC435 in other clinical studies
TMC435 is a once-daily (q.d.) protease inhibitor drug jointly developed by Tibotec Pharmaceuticals and, to treat chronic hepatitis C virus infections.
Three global clinical phase 3 response guided studies were recently initiated by Tibotec:
- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
In parallel to the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011. Phase 3 programs for TMC435 are also ongoing in Japan.
For additional information for these studies, please see http://www.clinicaltrials.gov
Conference call for analysts and investors:
There will be a conference call today, May 20 2011, for investors and analysts at 08.00 (EDT) / 13.00 (GMT) / 14.00 (CET) to discuss the data. To dial-in to the conference call please use the following numbers:
Participant Telephone Numbers: +1-718-354-1359 USA
+46(0)8-5051-3785 Sweden
+44(0)20-7136-2053 UK
Participant code 1156834
Soundbyte Replay Access Number: +44(0)20-7111-1244 UK
+1-347-366-9565 USA
+46(0)8-5051-3897 Sweden
Replay Access Code: 1156834#
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a protease inhibitor which has recently entered phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
Medivir is also marketing its first product, the unique cold sore product Xerese(TM)/Xerclear(R) which has recently been launched on the US market. Xerese(TM)/Xerclear(R), which is also approved in Europe, is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia and with Meda AB in North America, Canada and Mexico. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: http://www.medivir.com.
For more information about Medivir, please contact:
Medivir (http://www.medivir.com):
Rein Piir, CFO & VP Investor Relations Mobile: +46-708-537-292
Bertil Samuelsson, CSO Research & Development +46-8-54683100
M:Communications:
Mary-Jane Elliott / Amber Bielecka / Katja Toon +44(0)20-7920-2330
Medivir@mcomgroup.com
USA: Roland Tomforde +1-212-232-2356
SOURCE Medivir AB
Tuesday, April 26, 2011
Boehringer Ingelheim enrolls first patient in Phase 3 trial for BI 201335
Good news for BI as the first patient is enrolled in their phase 3 trials looking at HCV protease inhibitior BI 201335 in combinations with peg and riba. VERY nice to see that they will be looking at this compound in the HIV/HCV co-infected patient, an area that the first generation of protease inhibitors, Telaprevir and Boceprevir may be lacking in due to drug interaction and tolerability issues
Boehringer Ingelheim Announces Enrollment of First Patient in Phase 3 Trial for Lead Hepatitis C Compound
Development program has been granted FDA Fast Track designation
RIDGEFIELD, Conn., April 26, 2011 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced that enrollment has commenced at North American sites in its pivotal Phase 3 clinical trial program for BI 201335, the Company's investigational, oral protease inhibitor for the treatment of chronic hepatitis C virus (HCV). Phase 3 trials have begun recruiting to evaluate BI 201335 plus standard-of-care (SOC) in both treatment-naive and -experienced patients with chronic genotype-1 HCV, the most challenging HCV genotype to treat.(1) Results from the Phase 3 studies are expected in the first half of 2013.
The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the development program for BI 201335. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get important new drugs to patients earlier.(2)
"We are pleased to have begun enrolling patients at North American trial sites as we continue development of BI 201335," said Peter Piliero, M.D., executive director, Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "We look forward to initiating additional trials later this year in more patient populations, including HCV-HIV coinfected patients, as we continue to advance our HCV portfolio."
BI 201335 U.S. Phase 3 Trials
There are currently three Phase 3 trials enrolling patients around the world that together seek to enroll approximately 1,875 patients. Two of the three trials have U.S. trial sites that together plan to enroll approximately 495 patients.
In the U.S., Study 1220.47 will enroll approximately 370 treatment-naive genotype-1 HCV patients at 95 trial sites. This study will also include additional sites in Canada, Taiwan and Korea. Study 1220.7 will enroll approximately 125 treatment-experienced genotype-1 HCV patients who have failed at least 12 weeks of prior treatment with SOC at 40 trial sites in the U.S. This study also includes additional trial sites around the world. In treatment-naive patients (Study 1220.47), BI 201335 will be dosed once-daily at either 120 mg or 240 mg for 12 or 24 weeks in combination with 24 or 48 weeks of pegylated interferon and ribavirin, the current HCV SOC. In treatment-experienced patients (Study 1220.7) BI 201335 will be dosed once-daily at 240 mg for 12 or 24 weeks in combination with SOC for 48 weeks for prior partial and null responder patients. Patients with prior relapse will be dosed with BI 201335 once-daily at 240 mg for 12 or 24 weeks in combination with SOC for 24 or 48 weeks total duration. The primary endpoint of each trial is sustained viral response (SVR), which is considered viral cure.(3)
For more information about clinical trials involving BI 201335, please visit www.clinicaltrials.gov.
About Hepatitis C Virus (HCV)
HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant.(1,4) The number of individuals chronically infected with HCV globally has been estimated at 170 million, with three to four million new infections occurring each year.(5) Only about 20-45 percent of patients clear the virus in the acute phase.(5) Of the remaining chronically infected patients, 20 percent will develop cirrhosis within a mean of 20 years.(1) The mortality rate after cirrhosis has developed is two to five percent per year.(6) End-stage liver disease due to HCV infection currently represents the major cause for liver transplantation in the Western world.(1)
About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research program for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV. The company has a well established research center in Laval, Canada, dedicated to virology research since the early 1990's, and is committed to developing new therapies for virologic diseases with a high unmet medical need.
Boehringer Ingelheim in Hepatitis C Virus (HCV)
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim's own research and development, which has completed clinical trials through Phase 2b (SILEN-C studies). This Phase 2 program supports the investigation of BI 201335 in Phase 3 trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase 1 clinical trials. Phase 2 trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.
About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.
For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus.
References:
National Digestive Disease Information Clearing House (NDDICH), NIH. Chronic Hepatitis C: Current Disease Management. http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/index.htm.
U.S. Food and Drug Administration (FDA). Fast Track Designation Request Performance. http://www.fda.gov/AboutFDA/CentersOffices/CBER/ucm122932.htm.
American Association for the Study of Liver Disease Practice Guidelines: Diagnosis, Management, and Treatment of Hepatitis C: An Update. Hepatology, April 2009. http://www.natap.org/2009/HCV/aasld.pdf.
Centers for Disease Control and Prevention (CDC). Hepatitis C FAQs for the Public. http://www.cdc.gov/hepatitis/C/cFAQ.htm.
World Health Organization (WHO): Europe. Hepatitis: Hepatitis C. http://www.euro.who.int/en/what-we-do/health-topics/diseases-and-conditions/hepatitis/facts-and-figures/hepatitis-c.
Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009. http://cid.oxfordjournals.org/content/48/3/313.full.
SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.
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RELATED LINKS
http://us.boehringer-ingelheim.com
Boehringer Ingelheim Announces Enrollment of First Patient in Phase 3 Trial for Lead Hepatitis C Compound
Development program has been granted FDA Fast Track designation
RIDGEFIELD, Conn., April 26, 2011 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced that enrollment has commenced at North American sites in its pivotal Phase 3 clinical trial program for BI 201335, the Company's investigational, oral protease inhibitor for the treatment of chronic hepatitis C virus (HCV). Phase 3 trials have begun recruiting to evaluate BI 201335 plus standard-of-care (SOC) in both treatment-naive and -experienced patients with chronic genotype-1 HCV, the most challenging HCV genotype to treat.(1) Results from the Phase 3 studies are expected in the first half of 2013.
The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the development program for BI 201335. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get important new drugs to patients earlier.(2)
"We are pleased to have begun enrolling patients at North American trial sites as we continue development of BI 201335," said Peter Piliero, M.D., executive director, Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "We look forward to initiating additional trials later this year in more patient populations, including HCV-HIV coinfected patients, as we continue to advance our HCV portfolio."
BI 201335 U.S. Phase 3 Trials
There are currently three Phase 3 trials enrolling patients around the world that together seek to enroll approximately 1,875 patients. Two of the three trials have U.S. trial sites that together plan to enroll approximately 495 patients.
In the U.S., Study 1220.47 will enroll approximately 370 treatment-naive genotype-1 HCV patients at 95 trial sites. This study will also include additional sites in Canada, Taiwan and Korea. Study 1220.7 will enroll approximately 125 treatment-experienced genotype-1 HCV patients who have failed at least 12 weeks of prior treatment with SOC at 40 trial sites in the U.S. This study also includes additional trial sites around the world. In treatment-naive patients (Study 1220.47), BI 201335 will be dosed once-daily at either 120 mg or 240 mg for 12 or 24 weeks in combination with 24 or 48 weeks of pegylated interferon and ribavirin, the current HCV SOC. In treatment-experienced patients (Study 1220.7) BI 201335 will be dosed once-daily at 240 mg for 12 or 24 weeks in combination with SOC for 48 weeks for prior partial and null responder patients. Patients with prior relapse will be dosed with BI 201335 once-daily at 240 mg for 12 or 24 weeks in combination with SOC for 24 or 48 weeks total duration. The primary endpoint of each trial is sustained viral response (SVR), which is considered viral cure.(3)
For more information about clinical trials involving BI 201335, please visit www.clinicaltrials.gov.
About Hepatitis C Virus (HCV)
HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant.(1,4) The number of individuals chronically infected with HCV globally has been estimated at 170 million, with three to four million new infections occurring each year.(5) Only about 20-45 percent of patients clear the virus in the acute phase.(5) Of the remaining chronically infected patients, 20 percent will develop cirrhosis within a mean of 20 years.(1) The mortality rate after cirrhosis has developed is two to five percent per year.(6) End-stage liver disease due to HCV infection currently represents the major cause for liver transplantation in the Western world.(1)
About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research program for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV. The company has a well established research center in Laval, Canada, dedicated to virology research since the early 1990's, and is committed to developing new therapies for virologic diseases with a high unmet medical need.
Boehringer Ingelheim in Hepatitis C Virus (HCV)
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim's own research and development, which has completed clinical trials through Phase 2b (SILEN-C studies). This Phase 2 program supports the investigation of BI 201335 in Phase 3 trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase 1 clinical trials. Phase 2 trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.
About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.
For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus.
References:
National Digestive Disease Information Clearing House (NDDICH), NIH. Chronic Hepatitis C: Current Disease Management. http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/index.htm.
U.S. Food and Drug Administration (FDA). Fast Track Designation Request Performance. http://www.fda.gov/AboutFDA/CentersOffices/CBER/ucm122932.htm.
American Association for the Study of Liver Disease Practice Guidelines: Diagnosis, Management, and Treatment of Hepatitis C: An Update. Hepatology, April 2009. http://www.natap.org/2009/HCV/aasld.pdf.
Centers for Disease Control and Prevention (CDC). Hepatitis C FAQs for the Public. http://www.cdc.gov/hepatitis/C/cFAQ.htm.
World Health Organization (WHO): Europe. Hepatitis: Hepatitis C. http://www.euro.who.int/en/what-we-do/health-topics/diseases-and-conditions/hepatitis/facts-and-figures/hepatitis-c.
Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009. http://cid.oxfordjournals.org/content/48/3/313.full.
SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.
Back to top
RELATED LINKS
http://us.boehringer-ingelheim.com
Monday, April 25, 2011
Boceprevir Wins Favorable FDA Staff Review
MedPage Today covers FDA review of Boceprevir. Aside from the issues regarding Merck's definition of 'null responder', the predictive value of viral kinetics and the hemotologic issues with the drug, the only formal voting issue, however, is whether "the available data support approval" of boceprevir for treating HCV genotype 1 in combination with peginterferon and ribavirin.
Boceprevir Wins Favorable FDA Staff Review
By John Gever, Senior Editor, MedPage Today
Published: April 25, 2011
WASHINGTON -- The FDA's professional staff believes the investigational hepatitis C drug boceprevir (Victrelis) is effective and reasonably safe, according to a briefing document made public in advance of a Wednesday advisory committee meeting.
But before the agency approves the drug, it wants the panel's views on certain marketing claims that the drug's manufacturer, Merck, is proposing to make. These include the drug's efficacy in patients with "null" responses to the standard regimen of pegylated interferon and ribavirin as well as the benefits of so-called response-guided therapy.
The Antiviral Drugs Advisory Committee will also be asked to review risks of anemia and other hematologic abnormalities associated with boceprevir.
The drug is one of two hepatitis C virus (HCV) protease inhibitors that will be reviewed during a two-day meeting this week. The other is telaprevir -- no brand name has been proposed as yet -- which will have its day on Thursday.
The two drugs would be the first HCV protease inhibitors to reach the market. They have attracted major buzz among physicians and patients on the basis of excellent-looking clinical trial results, most recently from two of boceprevir's pivotal studies published in the New England Journal of Medicine last month.
These data suggest that adding one of the drugs to the standard peginterferon-ribavirin combination doubles or triples the sustained viral response rates.
For example, among treatment-naive patients in one of the boceprevir trials, 40% of a control group receiving the conventional regimen had a sustained response versus about 70% of patients with the protease inhibitor added.
A separate trial in patients with previous partial or unsustained responses to the standard regimen showed that 21% achieved a sustained response with a second round, whereas approximately 60% did with the addition of boceprevir.
In the briefing paper prepared for Wednesday's panel meeting, the FDA staff reviewers could find little to fault in these data.
But they did question Merck's arguments in favor of "response-guided therapy," particularly in African-American patients and raised concerns about the drug's hematologic side effects.
The core treatment regimen with boceprevir tested in the trials included a four-week lead-in period with peginterferon and ribavirin with boceprevir then added for 44 weeks. But some of the trials also included a regimen in which the duration of boceprevir treatment could be extended based on viral responses after eight and 24 weeks.
In particular, Merck would like the drug's label to allow longer treatment for patients with detectable HCV RNA at eight weeks but who achieve a full virologic response at 24 weeks, as some data suggested that such a regimen improves the sustained response rate.
But the FDA staff reviewers pointed to data in one of the trials indicating a slightly lower sustained-response rate in previous treatment failures receiving the response-guided therapy compared with fixed-duration treatment (59% versus 66%).
They also noted that black participants in a study of treatment-naive patients also had a lower sustained-response rate with response-guided therapy (42% versus 53%).
"The 11% numerical difference ... is of some concern and will be an issue for discussion," the briefing paper said.
Another issue is whether a proposed indication for patients who completely failed previous peginterferon-ribavirin therapy is justified, considering that such patients were excluded from trials of previously treated patients.
Merck is arguing that its major trial in treatment-naive patients included null responders, identified as those with negligible responses during the lead-in with standard therapy, and the drug's efficacy in this population can be gauged from those results.
However, the FDA reviewers indicated that responses at week four do not perfectly predict who will ultimately respond. The lack of a trial designed expressly to test the drug in null responders "raises questions about using [standard therapy] lead-in responses as a surrogate," they wrote in the briefing document.
About a quarter of the briefing document was devoted to boceprevir's adverse hematologic effects, primarily anemia but also including neutropenia and thrombocytopenia.
In the drug's two main phase III trials, half the patients taking the drug had nadir hemoglobin values of 10 g/dL or below and more than 40% required erythropoietin therapy -- with both rates about twice those seen in the control groups.
The other hematologic effects were far less common, but still a potential concern, according the briefing document.
Counting all cases, the incidence of neutropenia was about the same with or without boceprevir, but the drug was associated with a greater rate of serious cases. Eight of 1,057 patients taking the drug discontinued the study because of neutropenia compared with none in the control groups.
Similarly, severe thrombocytopenia was seen in 15 boceprevir-treated patients compared with three control patients.
The FDA plans to ask the advisory panel to comment on these adverse events, as well as to discuss postmarketing studies that Merck should conduct if the product is approved.
The only formal voting issue, however, is whether "the available data support approval" of boceprevir for treating HCV genotype 1 in combination with peginterferon and ribavirin.
Boceprevir Wins Favorable FDA Staff Review
By John Gever, Senior Editor, MedPage Today
Published: April 25, 2011
WASHINGTON -- The FDA's professional staff believes the investigational hepatitis C drug boceprevir (Victrelis) is effective and reasonably safe, according to a briefing document made public in advance of a Wednesday advisory committee meeting.
But before the agency approves the drug, it wants the panel's views on certain marketing claims that the drug's manufacturer, Merck, is proposing to make. These include the drug's efficacy in patients with "null" responses to the standard regimen of pegylated interferon and ribavirin as well as the benefits of so-called response-guided therapy.
The Antiviral Drugs Advisory Committee will also be asked to review risks of anemia and other hematologic abnormalities associated with boceprevir.
The drug is one of two hepatitis C virus (HCV) protease inhibitors that will be reviewed during a two-day meeting this week. The other is telaprevir -- no brand name has been proposed as yet -- which will have its day on Thursday.
The two drugs would be the first HCV protease inhibitors to reach the market. They have attracted major buzz among physicians and patients on the basis of excellent-looking clinical trial results, most recently from two of boceprevir's pivotal studies published in the New England Journal of Medicine last month.
These data suggest that adding one of the drugs to the standard peginterferon-ribavirin combination doubles or triples the sustained viral response rates.
For example, among treatment-naive patients in one of the boceprevir trials, 40% of a control group receiving the conventional regimen had a sustained response versus about 70% of patients with the protease inhibitor added.
A separate trial in patients with previous partial or unsustained responses to the standard regimen showed that 21% achieved a sustained response with a second round, whereas approximately 60% did with the addition of boceprevir.
In the briefing paper prepared for Wednesday's panel meeting, the FDA staff reviewers could find little to fault in these data.
But they did question Merck's arguments in favor of "response-guided therapy," particularly in African-American patients and raised concerns about the drug's hematologic side effects.
The core treatment regimen with boceprevir tested in the trials included a four-week lead-in period with peginterferon and ribavirin with boceprevir then added for 44 weeks. But some of the trials also included a regimen in which the duration of boceprevir treatment could be extended based on viral responses after eight and 24 weeks.
In particular, Merck would like the drug's label to allow longer treatment for patients with detectable HCV RNA at eight weeks but who achieve a full virologic response at 24 weeks, as some data suggested that such a regimen improves the sustained response rate.
But the FDA staff reviewers pointed to data in one of the trials indicating a slightly lower sustained-response rate in previous treatment failures receiving the response-guided therapy compared with fixed-duration treatment (59% versus 66%).
They also noted that black participants in a study of treatment-naive patients also had a lower sustained-response rate with response-guided therapy (42% versus 53%).
"The 11% numerical difference ... is of some concern and will be an issue for discussion," the briefing paper said.
Another issue is whether a proposed indication for patients who completely failed previous peginterferon-ribavirin therapy is justified, considering that such patients were excluded from trials of previously treated patients.
Merck is arguing that its major trial in treatment-naive patients included null responders, identified as those with negligible responses during the lead-in with standard therapy, and the drug's efficacy in this population can be gauged from those results.
However, the FDA reviewers indicated that responses at week four do not perfectly predict who will ultimately respond. The lack of a trial designed expressly to test the drug in null responders "raises questions about using [standard therapy] lead-in responses as a surrogate," they wrote in the briefing document.
About a quarter of the briefing document was devoted to boceprevir's adverse hematologic effects, primarily anemia but also including neutropenia and thrombocytopenia.
In the drug's two main phase III trials, half the patients taking the drug had nadir hemoglobin values of 10 g/dL or below and more than 40% required erythropoietin therapy -- with both rates about twice those seen in the control groups.
The other hematologic effects were far less common, but still a potential concern, according the briefing document.
Counting all cases, the incidence of neutropenia was about the same with or without boceprevir, but the drug was associated with a greater rate of serious cases. Eight of 1,057 patients taking the drug discontinued the study because of neutropenia compared with none in the control groups.
Similarly, severe thrombocytopenia was seen in 15 boceprevir-treated patients compared with three control patients.
The FDA plans to ask the advisory panel to comment on these adverse events, as well as to discuss postmarketing studies that Merck should conduct if the product is approved.
The only formal voting issue, however, is whether "the available data support approval" of boceprevir for treating HCV genotype 1 in combination with peginterferon and ribavirin.
Tuesday, April 12, 2011
Medivir to buy BioPhausia to "create a platform" for the launch of TMC435....
Medivir to buy BioPhausia for 62 million euros
World News | April 12, 2011
Medivir is to acquire fellow Swedish firm BioPhausia in a deal that will "create a platform" for the launch of its promising hepatitis C treatment.
Under the terms of the deal, Medivir is offering a mixture of cash and new shares, thus valuing BioPhausia at around 565 million Swedish kroner (62 million euros) or 1.65 crowns per share. The offer represents a 44% premium over the average price of BioPhausia shares over the last 30 days and the latter's board has unanimously recommended the offer.
The Huddinge-headquartered group says that BioPhausia will provide it with "complementary competencies in regulatory affairs, logistics, distribution, marketing, sales and quality assurance", plus a local presence in Sweden, Denmark and Finland. It also brings quite healthy revenues; turnover in 2010 came in at 506 million kroner, compared to Medivir's 62 million kroner.
Seeking sustainable profits
Ron Long, Medivir's chief executive, said the acquisition brings the firm closer to "achieving its goal of becoming a sustainably profitable, research-based specialty pharmaceutical company". He added that the BioPhausia team will "significantly advance our commercial capabilities as we prepare to realize full value from TMC435".
The latter is a once-daily, protease inhibitor for hepatitis C, which is partnered with Johnson & Johnson affiliate Tibotec and has recently reported positive interim data in three Phase IIb studies. It has moved to Phase III and Medivir has retained full commercial rights to TMC435 in the Nordic region.
Links
www.medivir.se
www.biophausia.se
World News | April 12, 2011
Medivir is to acquire fellow Swedish firm BioPhausia in a deal that will "create a platform" for the launch of its promising hepatitis C treatment.
Under the terms of the deal, Medivir is offering a mixture of cash and new shares, thus valuing BioPhausia at around 565 million Swedish kroner (62 million euros) or 1.65 crowns per share. The offer represents a 44% premium over the average price of BioPhausia shares over the last 30 days and the latter's board has unanimously recommended the offer.
The Huddinge-headquartered group says that BioPhausia will provide it with "complementary competencies in regulatory affairs, logistics, distribution, marketing, sales and quality assurance", plus a local presence in Sweden, Denmark and Finland. It also brings quite healthy revenues; turnover in 2010 came in at 506 million kroner, compared to Medivir's 62 million kroner.
Seeking sustainable profits
Ron Long, Medivir's chief executive, said the acquisition brings the firm closer to "achieving its goal of becoming a sustainably profitable, research-based specialty pharmaceutical company". He added that the BioPhausia team will "significantly advance our commercial capabilities as we prepare to realize full value from TMC435".
The latter is a once-daily, protease inhibitor for hepatitis C, which is partnered with Johnson & Johnson affiliate Tibotec and has recently reported positive interim data in three Phase IIb studies. It has moved to Phase III and Medivir has retained full commercial rights to TMC435 in the Nordic region.
Links
www.medivir.se
www.biophausia.se
Friday, April 1, 2011
Medivr/Tibotec QD HCV PI TMC435 Interim 24 week data from Phase 2b ASPIRE trial presented at EASL...
This is by far the cockiest press release I've read thus far that's associated with EASL, and I've had an eyeful. But the Medivir/Tibotec partnership has good reason to be at least somewhat arrogant. If they can keep these numbers looking as good 6 months post-treatment, then TMC435 will be the next gen DAA poised to usurp what looks to be Telaprevir’s throne. TMC435 looks to have extraordinary efficacy and tolerability in combination with PEG and Ribavirin at 24 weeks, boasting as much as 93.3% week 24 HCV RNA < 25 IU/mL in prior NULL responders in the 48 weeks TMC435 + Peg + RBV for 48 weeks arm (yes, NULL responders!) . Take a look at the tables here: http://www.prnewswire.com/news-releases/medivir-week-24-interim-results-from-tmc435-hepatitis-c-phase-2b-aspire-study-presented-at-easl-119040924.html
HUDDINGE, Sweden, April 1, 2011 /PRNewswire-FirstCall/ --
- Results Show Potent Antiviral Efficacy of Once Daily 150 mg TMC435 in Hepatitis C Patients Who Have Failed Earlier Treatment, Especially in Prior Null Responders, and Excellent Safety and Tolerability
Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, announces that their partner, Tibotec has presented the results of a planned Week 24 interim analysis of the phase 2b ASPIRE study for TMC435 in treatment experienced hepatitis C patients in a late-breaker session at the 46th Annual meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany.
Treatment experienced patients are known to be the most difficult to treat hepatitis C patient group.
TMC435 is a potent, once-daily, oral hepatitis C virus protease inhibitor which recently entered clinical phase 3 studies. The study enrolled patients chronically infected with genotype-1 hepatitis C virus (HCV) that had previously failed treatment with standard of care therapy (peginterferon and ribavarin). TMC435 is being jointly developed by Medivir and its partner Tibotec.
In this Week 24 interim analysis, treatment-experienced patients who failed peginterferon and ribavarin treatment achieved significantly greater virologic response rates following treatment with TMC435-containing regimen at all doses, compared with placebo. Results demonstrated that the TMC435 150 mg dose group showed the highest response, particularly in prior null responders. In this 150 mg dose group, HCV RNA levels were undetectable at week 24 for between 82% and 91% of the patients. Results also showed that there was no statistically relevant difference in safety and tolerability between the TMC435 and placebo treated groups.
Ron Long, CEO of Medivir, commented: "We are delighted that these strong results are to be presented at such a prestigious scientific conference as EASL. TMC435 continues to demonstrate why Medivir are so confident that hepatitis C treatment can be significantly changed by a more convenient, once daily protease inhibitor especially for treatment experienced patients. These data and the recent start of phase 3 clinical studies for TMC435, represent an exciting stage in Medivir's development as a significant player in the infectious disease market."
The ASPIRE study evaluates the effect of TMC435 in combination with standard of care (SoC) in 462 patients infected with the difficult to treat genotype-1 hepatitis C virus who had undergone and failed prior treatment with (SoC). The study includes patients that have relapsed, achieved partial response, or achieved no response (null responders) to treatment with standard of care. TMC435 was administered once daily at a dose of either 100 mg or 150mg given for either 12, 24, or 48 weeks in combination with standard of care. Standard of care treatment was continued until the study completion at week 48.
As well as the late-breaker ASPIRE data presented, a further three presentations will be made at EASL on TMC435. These include:
Oral presentation: Impact of IL28b genotype and pretreatment serum IP-10 in treatment-naive genotype-1 HCV patients treated with TMC435 in combination with peginterferona-2a and ribavirin in PILLAR study, J. Aerssens, which found that during 24 weeks of treatment, IL28B genotype and serum IP-10 were predictive of response in patients receiving standard of care (peginterferon and ribavirin) but had limited predictive value in patients treated with both TMC435 and peginterferon and ribavirin, therefore suggesting that TMC435, a potent, once daily oral protease inhibitor, may overcome the negative consequences of unfavourable host genotype encountered with pegIFN/RBV.
Poster presentation No.472: Pharmacokinetics of TMC435 in subjects with moderate hepatic impairment, V. Sekar, which found that no TMC435 dose adjustment was necessary for patients with moderate liver impairment.
Poster presentation No.1221: Treatment outcome and resistance analysis in HCV genotype 1 patients previously exposed to TMC435 monotherapy and re-treated with TMC435 in combination with pegifna-2a/ribavirin, O. Lenz, which found that viral variants in patients who had received TMC435 as a monotherapy were no longer detected over time and successful treatment after prior exposure to TMC435 with emergence of resistance variants was possible in 3/5 patients who had failed interferon-based therapy.
About TMC435 in other clinical studies
TMC435 is a once-daily (q.d.) protease inhibitor drug jointly developed by Medivir and Tibotec Pharmaceuticals, to treat chronic hepatitis C virus infections.
Three clinical phase 3 response guided studies were recently initiated:
- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
In parallel to the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
A phase 3 program for TMC435 has also recently been launched in Japan.
For additional information for these studies, please see http://www.clinicaltrials.gov
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a protease inhibitor which has recently entered phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
Medivir is also marketing its first product, the unique cold sore product Xerese(TM)/Xerclear(R) which has recently been launched on the US market. Xerese(TM)/Xerclear(R), which is also approved in Europe, is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia and with Meda AB in North America, Canada and Mexico. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: http://www.medivir.com.
For more information about Medivir, please contact:
Medivir (http://www.medivir.com):
Rein Piir, CFO & VP Investor Relations
Mobile: +46-708-537-292
Bertil Samuelsson, CFO Mobile: +46(70)576-13-50
M:Communications:
Mary-Jane Elliott / Amber Bielecka / Katja Toon
Medivir@mcomgroup.com
+44(0)20-7920 2330
USA: Roland Tomforde
+1-212-232-2356
Read the full press release with tables
HUDDINGE, Sweden, April 1, 2011 /PRNewswire-FirstCall/ --
- Results Show Potent Antiviral Efficacy of Once Daily 150 mg TMC435 in Hepatitis C Patients Who Have Failed Earlier Treatment, Especially in Prior Null Responders, and Excellent Safety and Tolerability
Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, announces that their partner, Tibotec has presented the results of a planned Week 24 interim analysis of the phase 2b ASPIRE study for TMC435 in treatment experienced hepatitis C patients in a late-breaker session at the 46th Annual meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany.
Treatment experienced patients are known to be the most difficult to treat hepatitis C patient group.
TMC435 is a potent, once-daily, oral hepatitis C virus protease inhibitor which recently entered clinical phase 3 studies. The study enrolled patients chronically infected with genotype-1 hepatitis C virus (HCV) that had previously failed treatment with standard of care therapy (peginterferon and ribavarin). TMC435 is being jointly developed by Medivir and its partner Tibotec.
In this Week 24 interim analysis, treatment-experienced patients who failed peginterferon and ribavarin treatment achieved significantly greater virologic response rates following treatment with TMC435-containing regimen at all doses, compared with placebo. Results demonstrated that the TMC435 150 mg dose group showed the highest response, particularly in prior null responders. In this 150 mg dose group, HCV RNA levels were undetectable at week 24 for between 82% and 91% of the patients. Results also showed that there was no statistically relevant difference in safety and tolerability between the TMC435 and placebo treated groups.
Ron Long, CEO of Medivir, commented: "We are delighted that these strong results are to be presented at such a prestigious scientific conference as EASL. TMC435 continues to demonstrate why Medivir are so confident that hepatitis C treatment can be significantly changed by a more convenient, once daily protease inhibitor especially for treatment experienced patients. These data and the recent start of phase 3 clinical studies for TMC435, represent an exciting stage in Medivir's development as a significant player in the infectious disease market."
The ASPIRE study evaluates the effect of TMC435 in combination with standard of care (SoC) in 462 patients infected with the difficult to treat genotype-1 hepatitis C virus who had undergone and failed prior treatment with (SoC). The study includes patients that have relapsed, achieved partial response, or achieved no response (null responders) to treatment with standard of care. TMC435 was administered once daily at a dose of either 100 mg or 150mg given for either 12, 24, or 48 weeks in combination with standard of care. Standard of care treatment was continued until the study completion at week 48.
As well as the late-breaker ASPIRE data presented, a further three presentations will be made at EASL on TMC435. These include:
Oral presentation: Impact of IL28b genotype and pretreatment serum IP-10 in treatment-naive genotype-1 HCV patients treated with TMC435 in combination with peginterferona-2a and ribavirin in PILLAR study, J. Aerssens, which found that during 24 weeks of treatment, IL28B genotype and serum IP-10 were predictive of response in patients receiving standard of care (peginterferon and ribavirin) but had limited predictive value in patients treated with both TMC435 and peginterferon and ribavirin, therefore suggesting that TMC435, a potent, once daily oral protease inhibitor, may overcome the negative consequences of unfavourable host genotype encountered with pegIFN/RBV.
Poster presentation No.472: Pharmacokinetics of TMC435 in subjects with moderate hepatic impairment, V. Sekar, which found that no TMC435 dose adjustment was necessary for patients with moderate liver impairment.
Poster presentation No.1221: Treatment outcome and resistance analysis in HCV genotype 1 patients previously exposed to TMC435 monotherapy and re-treated with TMC435 in combination with pegifna-2a/ribavirin, O. Lenz, which found that viral variants in patients who had received TMC435 as a monotherapy were no longer detected over time and successful treatment after prior exposure to TMC435 with emergence of resistance variants was possible in 3/5 patients who had failed interferon-based therapy.
About TMC435 in other clinical studies
TMC435 is a once-daily (q.d.) protease inhibitor drug jointly developed by Medivir and Tibotec Pharmaceuticals, to treat chronic hepatitis C virus infections.
Three clinical phase 3 response guided studies were recently initiated:
- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
In parallel to the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
A phase 3 program for TMC435 has also recently been launched in Japan.
For additional information for these studies, please see http://www.clinicaltrials.gov
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a protease inhibitor which has recently entered phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
Medivir is also marketing its first product, the unique cold sore product Xerese(TM)/Xerclear(R) which has recently been launched on the US market. Xerese(TM)/Xerclear(R), which is also approved in Europe, is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia and with Meda AB in North America, Canada and Mexico. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: http://www.medivir.com.
For more information about Medivir, please contact:
Medivir (http://www.medivir.com):
Rein Piir, CFO & VP Investor Relations
Mobile: +46-708-537-292
Bertil Samuelsson, CFO Mobile: +46(70)576-13-50
M:Communications:
Mary-Jane Elliott / Amber Bielecka / Katja Toon
Medivir@mcomgroup.com
+44(0)20-7920 2330
USA: Roland Tomforde
+1-212-232-2356
Read the full press release with tables
Thursday, March 17, 2011
Boehringer Ingelheim to show final Phase IIb data for it's BI 20133 protease inhibitor...
New data from the Boehringer Ingelheim hepatitis C virus (HCV) portfolio will be presented in oral scientific sessions at the International Liver CongressTM 2011, the 46th Annual Meeting of the European Association for the Study of the Liver (EASL), taking place 30 March-3 April in Berlin, Germany. The data will include final results from SILEN-C1 and SILEN-C2, two Phase IIb studies evaluating one of Boehringer Ingelheim’s investigational compounds for Hepatitis C treatment, the once-daily, oral protease inhibitor BI 201335 in combination with the current standard-of-care (pegylated-interferon and ribavirin).
Oral presentations (Friday, 1 April, 2011; Parallel Session: HCV Drug Development, Hall 1)
SILEN-C1: Sustained Virologic Response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in treatment-naïve patients with chronic genotype 1 HCV infection
(Abstract 60. M. Sulkowski, et al. 16:00h - 16:15h)
SILEN-C2: Sustained Virologic Response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in chronic HCV genotype-1 patients with non-response to P/R
(Abstract 66. M. Sulkowski, et al. 17:30h - 17:45h)
Boehringer Ingelheim is continuing its long heritage in virology and is dedicated to developing new medicines to improve treatment for HCV patients. BI 201335 is part of a growing HCV portfolio that is being investigated with the aim of identifying a simpler HCV cure, overcoming the challenges of current treatments.
Additional HCV studies to be presented at EASL
SVR and Pharmacokinetics of the HCV protease inhibitor BI201335 with PegIFN/RBV in HCV genotype-1 patients with compensated liver cirrhosis and non-response to previous PegIFN/RBV
(Poster 1231. S. Pol, et al.; Saturday, 2 April, 2011, 09:00h - 18:00h)
Mechanisms of isolated unconjugated hyperbilirubinemia induced by the HCV NS3/4A protease inhibitor BI201335 (Poster 1236. R. Sane, et al.;Saturday, 2 April, 2011, 09:00h - 18:00h)
BI201335 Pharmacokinetics and early effect on viral load in HCV genotype-1 patients
(Poster 1249. C. Yong, et al.;Saturday, April 2, 2011, 09:00h - 18:00h)
Preclinical Characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BILB 1941 (Poster 1215. G. Kukolj et. al.; Friday, 30 March, 2011, 09:00h - 18:00h)
The abstracts can be accessed through the EASL website, www.easl.eu.
For more information on BI’s hepatitis portfolio, please visit www.boehringer-ingelheim.com and follow us on Twitter. www.twitter.com/boehringer.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
Within the company’s global research network, Virology is one of the seven R&D areas with focus on Hepatitis C.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
Oral presentations (Friday, 1 April, 2011; Parallel Session: HCV Drug Development, Hall 1)
SILEN-C1: Sustained Virologic Response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in treatment-naïve patients with chronic genotype 1 HCV infection
(Abstract 60. M. Sulkowski, et al. 16:00h - 16:15h)
SILEN-C2: Sustained Virologic Response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in chronic HCV genotype-1 patients with non-response to P/R
(Abstract 66. M. Sulkowski, et al. 17:30h - 17:45h)
Boehringer Ingelheim is continuing its long heritage in virology and is dedicated to developing new medicines to improve treatment for HCV patients. BI 201335 is part of a growing HCV portfolio that is being investigated with the aim of identifying a simpler HCV cure, overcoming the challenges of current treatments.
Additional HCV studies to be presented at EASL
SVR and Pharmacokinetics of the HCV protease inhibitor BI201335 with PegIFN/RBV in HCV genotype-1 patients with compensated liver cirrhosis and non-response to previous PegIFN/RBV
(Poster 1231. S. Pol, et al.; Saturday, 2 April, 2011, 09:00h - 18:00h)
Mechanisms of isolated unconjugated hyperbilirubinemia induced by the HCV NS3/4A protease inhibitor BI201335 (Poster 1236. R. Sane, et al.;Saturday, 2 April, 2011, 09:00h - 18:00h)
BI201335 Pharmacokinetics and early effect on viral load in HCV genotype-1 patients
(Poster 1249. C. Yong, et al.;Saturday, April 2, 2011, 09:00h - 18:00h)
Preclinical Characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BILB 1941 (Poster 1215. G. Kukolj et. al.; Friday, 30 March, 2011, 09:00h - 18:00h)
The abstracts can be accessed through the EASL website, www.easl.eu.
For more information on BI’s hepatitis portfolio, please visit www.boehringer-ingelheim.com and follow us on Twitter. www.twitter.com/boehringer.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
Within the company’s global research network, Virology is one of the seven R&D areas with focus on Hepatitis C.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
Wednesday, February 23, 2011
Medivir announces SVR24 in TMC435 in Phase 2b Treatment-naive patient population....
A might bit too early to fully put on my 'bullish' hat, still have to see what the final SVR will look like in all the arms (especially the placebo SOC arm), but TMC435 plus peg/riba looks awfully strong. Add in once daily dosing and equal DC's between placebo arm and TMC435 arms... the early data in this trial looks promising. We'll all be anxiously awaiting results for Medivir's ASPIRE trial in treatment-experienced patients coming in Q2 of this year.
HUDDINGE, Sweden, February 22, 2011 /PRNewswire-FirstCall/ -- Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, announces today further positive results from the phase 2b PILLAR (C205) study of TMC435 in treatment-naive patients with hepatitis C virus (HCV) genotype-1.
- TMC435 was safe and well tolerated with no clinically
relevant differences in adverse events between treatment groups and
standard of care (SoC).
- In the TMC435 treatment groups 83% of patients were able to stop
all therapy at week 24
- Potent and consistent antiviral efficacy was demonstrated with
SVR24 rates of up to 84%
"We are very pleased by both the efficacy and safety shown by TMC435 in this 48-Week interim analysis. With the additional features of once daily dosing, TMC435 also has a more convenient and competitive dosing regimen" stated Bertil Samuelsson, CSO of Medivir. "The recently published start of three global phase 3 clinical trials is an important milestone in the continued development of TMC435. We are now looking forward to the 48-week interim data from the phase 2b trial C206 (ASPIRE) in treatment-experienced patients during Q2 2011."
The 48-week interim results from the 5-arm phase 2b response guided PILLAR study in 386 treatment-naive patients showed further consistent high antiviral activity, and the good safety and tolerability previously demonstrated was confirmed. The 24-week (EOT) interim results were presented at the AASLD conference in Boston, MA, in November 2010.
Study design
In the PILLAR study, 75mg or 150mg TMC435 was given for either 12 or 24 weeks in combination with 24 weeks of ribavirin and pegIFNalpha-2A, the current standard of care (SoC). Patients in the TMC435 arms stopped all treatment at week 24 if certain predefined response-guided criteria were met. In the TMC435 treatment groups 83% of patients were able to stop all therapy at week 24. Patients who did not meet the above response-guided criteria continued with SoC until week 48 as did the placebo group.
Evaluation criteria
A protocol-defined interim analysis was performed when all patients completed their Week 48 visit or discontinued treatment earlier. Final SVR4 and SVR24 data were available for 98% (303/309; n/N) and 93% (288/309; n/N) of TMC435 treated patients, respectively. SVR24 is determined 24 weeks after the planned end of treatment (EoT) and was therefore not yet available for the patients in the placebo group and for some of those in the TMC435 group who received 48 weeks of treatment. SVR4, which is determined 4 weeks after the planned EoT, was available for 77% (59/77; n/M) of the patients in the placebo group.
Results - Efficacy
Potent and sustained antiviral efficacy was demonstrated in the SVR4 and SVR24 rates with no major differences between TMC435 doses or length of triple therapy. At week 4 after cessation of treatment 87.2%, 86.5%, 84.9% and 88.5% of patients taking TMC435 and Peg-IFN/RBV (SoC) achieved undetectable HCV RNA levels. At week 24 after cessation of treatment 83.6%, 76.1%, 83.1% and 84.4% of patients taking TMC435 and Peg-IFN/RBV (SoC) achieved undetectable HCV RNA levels, i.e. SVR24. At week 4 after cessation of treatment 71.2% in the placebo SoC group had achieved undetectable HCV RNA levels.
The results are derived from an intent-to-treat (ITT) analysis of the patient population who took at least one dose of the study medication and who reached the criteria for stopping all treatment at 24 weeks (83%).
Sustained Virological Response 4 and 24 Weeks after Planned End of
Treatment (EoT);
TMC435 TMC435 TMC435 TMC435 Placebo
12PR24 24PR24 12PR24 24PR24
75mg q.d. 75mg q.d. 150mg q.d. 150mg q.d.
% (n/N) N=78 N=75 N=77 N=79 N=77
SVR4 87.2 (68/78) 86.5 (64/74) 84.9 (62/73) 88.5 (69/78) 71.2 (42/59)
SVR24 83.6 (61/73) 76.1 (51/67) 83.1 (59/71) 84.4 (65/77) N/A
* < 25 log10 IU/mL undetectable
q.d.: once daily, PR: pegIFNalpha-2A and ribavirin,
SVR4 and SVR24: patients with undetectable HCV RNA 4 and 24 weeks after planned EoT, respectively. N/A: Patients in the control arm continue SoC until Week 48 and SVR24 data was not available
Results - Safety and Tolerability
TMC435 was generally safe and well tolerated and overall incidence of adverse events (AEs) was similar across treatment groups. AEs leading to discontinuation of TMC435 or placebo treatment were reported in 7.8% of the placebo subjects and in 7.1% of the TMC435 treated subjects. In the safety analyses, special attention was given to the following AEs of interest: hepatobiliary AEs, pruritus, rash, anemia, and cardiac events. For each category of AEs of interest; the incidence was similar between TMC435 and placebo.
In laboratory parameters, there were no clinically relevant differences between any TMC435 groups and placebo except for mild on treatment reversible bilirubin elevations (total, direct and indirect) in the 150 mg TMC435 arm, which were normalized after TMC435 dosing was completed. There were no meaningful differences between treatment groups for any of the other laboratory parameters. Significant and rapid decreases in transaminases (ALT and AST) were observed in all TMC435 treatment groups.
HUDDINGE, Sweden, February 22, 2011 /PRNewswire-FirstCall/ -- Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, announces today further positive results from the phase 2b PILLAR (C205) study of TMC435 in treatment-naive patients with hepatitis C virus (HCV) genotype-1.
- TMC435 was safe and well tolerated with no clinically
relevant differences in adverse events between treatment groups and
standard of care (SoC).
- In the TMC435 treatment groups 83% of patients were able to stop
all therapy at week 24
- Potent and consistent antiviral efficacy was demonstrated with
SVR24 rates of up to 84%
"We are very pleased by both the efficacy and safety shown by TMC435 in this 48-Week interim analysis. With the additional features of once daily dosing, TMC435 also has a more convenient and competitive dosing regimen" stated Bertil Samuelsson, CSO of Medivir. "The recently published start of three global phase 3 clinical trials is an important milestone in the continued development of TMC435. We are now looking forward to the 48-week interim data from the phase 2b trial C206 (ASPIRE) in treatment-experienced patients during Q2 2011."
The 48-week interim results from the 5-arm phase 2b response guided PILLAR study in 386 treatment-naive patients showed further consistent high antiviral activity, and the good safety and tolerability previously demonstrated was confirmed. The 24-week (EOT) interim results were presented at the AASLD conference in Boston, MA, in November 2010.
Study design
In the PILLAR study, 75mg or 150mg TMC435 was given for either 12 or 24 weeks in combination with 24 weeks of ribavirin and pegIFNalpha-2A, the current standard of care (SoC). Patients in the TMC435 arms stopped all treatment at week 24 if certain predefined response-guided criteria were met. In the TMC435 treatment groups 83% of patients were able to stop all therapy at week 24. Patients who did not meet the above response-guided criteria continued with SoC until week 48 as did the placebo group.
Evaluation criteria
A protocol-defined interim analysis was performed when all patients completed their Week 48 visit or discontinued treatment earlier. Final SVR4 and SVR24 data were available for 98% (303/309; n/N) and 93% (288/309; n/N) of TMC435 treated patients, respectively. SVR24 is determined 24 weeks after the planned end of treatment (EoT) and was therefore not yet available for the patients in the placebo group and for some of those in the TMC435 group who received 48 weeks of treatment. SVR4, which is determined 4 weeks after the planned EoT, was available for 77% (59/77; n/M) of the patients in the placebo group.
Results - Efficacy
Potent and sustained antiviral efficacy was demonstrated in the SVR4 and SVR24 rates with no major differences between TMC435 doses or length of triple therapy. At week 4 after cessation of treatment 87.2%, 86.5%, 84.9% and 88.5% of patients taking TMC435 and Peg-IFN/RBV (SoC) achieved undetectable HCV RNA levels. At week 24 after cessation of treatment 83.6%, 76.1%, 83.1% and 84.4% of patients taking TMC435 and Peg-IFN/RBV (SoC) achieved undetectable HCV RNA levels, i.e. SVR24. At week 4 after cessation of treatment 71.2% in the placebo SoC group had achieved undetectable HCV RNA levels.
The results are derived from an intent-to-treat (ITT) analysis of the patient population who took at least one dose of the study medication and who reached the criteria for stopping all treatment at 24 weeks (83%).
Sustained Virological Response 4 and 24 Weeks after Planned End of
Treatment (EoT);
TMC435 TMC435 TMC435 TMC435 Placebo
12PR24 24PR24 12PR24 24PR24
75mg q.d. 75mg q.d. 150mg q.d. 150mg q.d.
% (n/N) N=78 N=75 N=77 N=79 N=77
SVR4 87.2 (68/78) 86.5 (64/74) 84.9 (62/73) 88.5 (69/78) 71.2 (42/59)
SVR24 83.6 (61/73) 76.1 (51/67) 83.1 (59/71) 84.4 (65/77) N/A
* < 25 log10 IU/mL undetectable
q.d.: once daily, PR: pegIFNalpha-2A and ribavirin,
SVR4 and SVR24: patients with undetectable HCV RNA 4 and 24 weeks after planned EoT, respectively. N/A: Patients in the control arm continue SoC until Week 48 and SVR24 data was not available
Results - Safety and Tolerability
TMC435 was generally safe and well tolerated and overall incidence of adverse events (AEs) was similar across treatment groups. AEs leading to discontinuation of TMC435 or placebo treatment were reported in 7.8% of the placebo subjects and in 7.1% of the TMC435 treated subjects. In the safety analyses, special attention was given to the following AEs of interest: hepatobiliary AEs, pruritus, rash, anemia, and cardiac events. For each category of AEs of interest; the incidence was similar between TMC435 and placebo.
In laboratory parameters, there were no clinically relevant differences between any TMC435 groups and placebo except for mild on treatment reversible bilirubin elevations (total, direct and indirect) in the 150 mg TMC435 arm, which were normalized after TMC435 dosing was completed. There were no meaningful differences between treatment groups for any of the other laboratory parameters. Significant and rapid decreases in transaminases (ALT and AST) were observed in all TMC435 treatment groups.
Monday, December 20, 2010
Janssen Seeks European Marketing Authorization For Investigational Hepatitis C Treatment Telaprevir
It will be interesting to see how Tibotec supports Telaprevir in Europe, with a possible competitor, TMC435 waiting in the wings. Vertex, with it's relatively rich, advanced pipeline in HCV, esp with the relatively drug-interaction free HCV non-nuc VX-222 that would be a nice complementary acquisition for the J&J family. According to outside sources, Merck only expects a 35% marketshare for Boceprevir vs Telaprevir. Given the potential baggage that comes along with Telaprevir with Q8h dosing, highly variable PK at q12h and the potential severity of the rash, esp in people of color, Merck (for once) may be underestimating the market potential of Boceprevir - Chris
Janssen-Cilag International NV announced the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for telaprevir, an investigational, oral, direct-acting antiviral for the treatment of chronic genotype 1 hepatitis C virus (HCV), the most common form of the virus. Telaprevir is a potent and selective protease inhibitor (PI), which when combined with pegylated-interferon and ribavirin (the current treatment standard), shows activity in patients that are new to treatment and who have been previously treated but were not cured, including partial responders, relapsers and those who have had little or no response (null responders) to the current standard of treatment.
The EMA has accepted telaprevir for accelerated assessment, which is granted to quicken access to innovative, new medicines of major public-health interest. Tibotec BVBA, a global research and development company with specific experience in virology, is developing telaprevir in collaboration with Vertex Pharmaceuticals. Tibotec BVBA is an affiliate company of Janssen.
"The EMA submission for telaprevir is a landmark in the treatment of HCV and demonstrates our dedication to addressing unmet medical needs by developing innovative treatments for infectious diseases," said Johan Van Hoof, Global Therapeutic Area Head Infectious Diseases and Vaccines at Janssen. "Above all, it is an important step towards making telaprevir available to people living with HCV."
It is estimated that 170 million people are living with HCV around the world, including more than five million in Europe. Chronic HCV can result in serious long-term health problems, and an estimated 30 percent of patients will develop progressive liver disease, including cirrhosis (damage and scarring of the liver), which places them at risk for liver insufficiency and liver cancer. HCV is the most common cause of liver transplant in Europe.
The current standard of care for HCV genotype 1 patients, pegylated-interferon and ribavirin, is administered for 48 weeks and only 40 to 50 percent of genotype 1 patients achieve a sustained virologic response (SVR), defined as achieving undetectable levels of the virus in the blood for six months after completion of treatment, and considered an indicator of cure. Re-treatment with pegylated-interferon and ribavirin in patients who have previously failed this treatment shows only limited success. ,
The EMA submission is supported by results from three phase 3 studies, which compared telaprevir in combination with the current standard of treatment to the current standard of treatment alone in HCV genotype 1 patients. Results were very positive:
- Significantly higher SVR rates were observed in treatment-naïve patients treated with telaprevir compared to the current standard treatment of pegylated-interferon and ribavirin (75 percent vs. 44 percent)
- The majority of patients were cured by week 24, which is half the duration of therapy with the current standard of treatment8,
- There was a three-fold increase in cure rates (65 percent vs. 17 percent) across all types of previously treated patients who were given telaprevir compared to the current treatment standard, including prior null responders (31 percent vs. 5 percent) 10
- The most common adverse events in the telaprevir-based treatment groups were fatigue, pruritus, nausea, headache, anemia, rash, influenza-like illness, insomnia, fever and diarrhea. The majority of these adverse events were mild to moderate.8,9,10
"Current treatment for hepatitis is lengthy and only effective for approximately half of treatment-naïve patients, and even fewer patients who failed previous treatment," commented Stefan Zeuzem, Professor of Medicine and Chief, department of medicine, J W Goethe University Hospital, Frankfurt. "If approved, telaprevir would help to significantly improve cure rates and shorten treatment duration for many people living with HCV, compared to current standard treatment."
About the Telaprevir Development Program
To date, more than 2,500 people with HCV genotype 1 have received telaprevir-based therapy (telaprevir combined with the current standard of treatment) as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE trials.8,9,10 The telaprevir clinical development program is the largest conducted to date for any investigational direct-acting antiviral hepatitis C therapy.
- ADVANCE evaluated telaprevir-based regimens in approximately 1,088 treatment-naïve patients with chronic HCV infection. Data from the ADVANCE trial were presented at the 2010 American Association for the Study of Liver Diseases (AASLD) annual meeting in November 2010.8
- ILLUMINATE evaluated the benefits of extending telaprevir-based therapy in 540 treatment-naïve patients whose HCV was undetectable at weeks 4 and 12 of treatment. 322 of these patients were randomized to receive 24 or 48 weeks of treatment, and it was found that there was no benefit to extending treatment to 48 weeks. Data from the ILLUMINATE meeting were presented at AASLD in November 2010.9
- REALIZE evaluated telaprevir-based regimens in approximately 650 treatment-failure HCV patients. Data from the REALIZE trial will likely be published in 2011.
Telaprevir is being developed by Tibotec BVBA, an affiliate company of Janssen, in collaboration with Vertex Pharmaceuticals and Mitsubishi Tanabe Pharma for the treatment of genotype 1 HCV in combination with pegylated-interferon and ribavirin in both patients who have failed prior treatment and those who have never been treated. Tibotec BVBA has the commercialisation rights for telaprevir in Europe, Latin America, the Middle East, Africa, India, Australia and New Zealand, pending approval by the respective regulatory authorities. Vertex will commercialise telaprevir in the U.S., Canada and Mexico and Mitsubishi Tanabe Pharma has rights to commercialise telaprevir in Japan and certain Far East countries.
About Tibotec BVBA
Tibotec BVBA is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and HCV drugs, and anti-infectives for diseases of high unmet medical need.
Janssen-Cilag International NV announced the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for telaprevir, an investigational, oral, direct-acting antiviral for the treatment of chronic genotype 1 hepatitis C virus (HCV), the most common form of the virus. Telaprevir is a potent and selective protease inhibitor (PI), which when combined with pegylated-interferon and ribavirin (the current treatment standard), shows activity in patients that are new to treatment and who have been previously treated but were not cured, including partial responders, relapsers and those who have had little or no response (null responders) to the current standard of treatment.
The EMA has accepted telaprevir for accelerated assessment, which is granted to quicken access to innovative, new medicines of major public-health interest. Tibotec BVBA, a global research and development company with specific experience in virology, is developing telaprevir in collaboration with Vertex Pharmaceuticals. Tibotec BVBA is an affiliate company of Janssen.
"The EMA submission for telaprevir is a landmark in the treatment of HCV and demonstrates our dedication to addressing unmet medical needs by developing innovative treatments for infectious diseases," said Johan Van Hoof, Global Therapeutic Area Head Infectious Diseases and Vaccines at Janssen. "Above all, it is an important step towards making telaprevir available to people living with HCV."
It is estimated that 170 million people are living with HCV around the world, including more than five million in Europe. Chronic HCV can result in serious long-term health problems, and an estimated 30 percent of patients will develop progressive liver disease, including cirrhosis (damage and scarring of the liver), which places them at risk for liver insufficiency and liver cancer. HCV is the most common cause of liver transplant in Europe.
The current standard of care for HCV genotype 1 patients, pegylated-interferon and ribavirin, is administered for 48 weeks and only 40 to 50 percent of genotype 1 patients achieve a sustained virologic response (SVR), defined as achieving undetectable levels of the virus in the blood for six months after completion of treatment, and considered an indicator of cure. Re-treatment with pegylated-interferon and ribavirin in patients who have previously failed this treatment shows only limited success. ,
The EMA submission is supported by results from three phase 3 studies, which compared telaprevir in combination with the current standard of treatment to the current standard of treatment alone in HCV genotype 1 patients. Results were very positive:
- Significantly higher SVR rates were observed in treatment-naïve patients treated with telaprevir compared to the current standard treatment of pegylated-interferon and ribavirin (75 percent vs. 44 percent)
- The majority of patients were cured by week 24, which is half the duration of therapy with the current standard of treatment8,
- There was a three-fold increase in cure rates (65 percent vs. 17 percent) across all types of previously treated patients who were given telaprevir compared to the current treatment standard, including prior null responders (31 percent vs. 5 percent) 10
- The most common adverse events in the telaprevir-based treatment groups were fatigue, pruritus, nausea, headache, anemia, rash, influenza-like illness, insomnia, fever and diarrhea. The majority of these adverse events were mild to moderate.8,9,10
"Current treatment for hepatitis is lengthy and only effective for approximately half of treatment-naïve patients, and even fewer patients who failed previous treatment," commented Stefan Zeuzem, Professor of Medicine and Chief, department of medicine, J W Goethe University Hospital, Frankfurt. "If approved, telaprevir would help to significantly improve cure rates and shorten treatment duration for many people living with HCV, compared to current standard treatment."
About the Telaprevir Development Program
To date, more than 2,500 people with HCV genotype 1 have received telaprevir-based therapy (telaprevir combined with the current standard of treatment) as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE trials.8,9,10 The telaprevir clinical development program is the largest conducted to date for any investigational direct-acting antiviral hepatitis C therapy.
- ADVANCE evaluated telaprevir-based regimens in approximately 1,088 treatment-naïve patients with chronic HCV infection. Data from the ADVANCE trial were presented at the 2010 American Association for the Study of Liver Diseases (AASLD) annual meeting in November 2010.8
- ILLUMINATE evaluated the benefits of extending telaprevir-based therapy in 540 treatment-naïve patients whose HCV was undetectable at weeks 4 and 12 of treatment. 322 of these patients were randomized to receive 24 or 48 weeks of treatment, and it was found that there was no benefit to extending treatment to 48 weeks. Data from the ILLUMINATE meeting were presented at AASLD in November 2010.9
- REALIZE evaluated telaprevir-based regimens in approximately 650 treatment-failure HCV patients. Data from the REALIZE trial will likely be published in 2011.
Telaprevir is being developed by Tibotec BVBA, an affiliate company of Janssen, in collaboration with Vertex Pharmaceuticals and Mitsubishi Tanabe Pharma for the treatment of genotype 1 HCV in combination with pegylated-interferon and ribavirin in both patients who have failed prior treatment and those who have never been treated. Tibotec BVBA has the commercialisation rights for telaprevir in Europe, Latin America, the Middle East, Africa, India, Australia and New Zealand, pending approval by the respective regulatory authorities. Vertex will commercialise telaprevir in the U.S., Canada and Mexico and Mitsubishi Tanabe Pharma has rights to commercialise telaprevir in Japan and certain Far East countries.
About Tibotec BVBA
Tibotec BVBA is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and HCV drugs, and anti-infectives for diseases of high unmet medical need.
Tuesday, December 7, 2010
Medivir raises $41 million from institutional investors for TMC435 and beyond....
Medivir Creates Runway for TMC435 with $41M Placement
By Nuala Moran
BioWorld International Correspondent
LONDON – Medivir AB raised €30.8 million (US$41 million) in a private placement that brings in international institutional investors in the lead up to the start of Phase III trials of the lead product, TMC435, a protease inhibitor for treating hepatitis C (HCV) infections.
"The strategy is to broaden the shareholder base outside Scandinavia," said Rein Piir, CFO. All the new shareholders are, "high-quality, top-rank, U.S., Swiss, Dutch and UK investors," he told a teleconference held to discuss the placement.
In total, Huddinge, Denmark-based Medivir issued 2.25 million new shares at SEK125 ($18.23) each to 30 international institutional investors, plus some institutions in Sweden that were not already shareholders.
That represented a 7.9 percent dilution for existing investors. More than two-thirds of the new shares were taken up by international investors. Medivir is quoted on the Nasdaq OMX Exchange in Stockholm.
"This will enable Medivir to strengthen its R&D and take a higher amount of value going forward, by doing joint ventures rather than licensing, and [allowing us to] take products further," Piir said.
Medivir announced its intention of doing the placing in March when it sought approval from shareholders, but its ability to do so rests on positive Phase IIb data for TMC 435. The product is partnered by Johnson & Johnson subsidiary Tibotec Pharmaceuticals Ltd., with Medivir retaining rights in Nordic markets.
Last month, Medivir announced positive interim data from Aspire, a Phase IIb study of TMC 435 as a once-daily therapy in 462 HCV patients who had been treated previously with pegylated interferon (peg-INF).
TMC 435, added to standard of care, increased the number of patients whose HCV levels were undetectable at 24 weeks.
Across four treatment groups, between 79 percent and 86 percent of patients were able to stop taking any therapy at 24 weeks. Patients in the study were infected with genotype 1 HCV, which is hard to treat.
The product also had positive results in a 386-subject Phase IIb study in treatment-naïve patients, which reported in July. Here, 83 percent of those treated with TMC 435 were able to stop all therapy at 24 weeks.
Those results were presented by Tibotec at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, in October.
"We witnessed enthusiasm for TMC435 at the AASLD clinical meeting, which together with positive Phase IIb Aspire results, boosts our confidence and price target, by 6 percent," noted Peter Welford, equity analyst at Jeffries in London
The shares closed at SEK120 on Dec. 3, the day the completion of the placing was announced. Welford added that Medivir is, "The European biotech best placed to benefit from broad enthusiasm for the wave of new blockbuster hepatitis C therapies reaching the market."
Building on the success of TMC 435, the company has other HCV products coming through its pipeline. "Investors are supporting Medivir in efforts to become a leading player in HCV," Piir said.
The company also intends to apply its technology to new therapeutic areas. "We are in discussion on [doing] this in a joint venture structure," Piir added.
By Nuala Moran
BioWorld International Correspondent
LONDON – Medivir AB raised €30.8 million (US$41 million) in a private placement that brings in international institutional investors in the lead up to the start of Phase III trials of the lead product, TMC435, a protease inhibitor for treating hepatitis C (HCV) infections.
"The strategy is to broaden the shareholder base outside Scandinavia," said Rein Piir, CFO. All the new shareholders are, "high-quality, top-rank, U.S., Swiss, Dutch and UK investors," he told a teleconference held to discuss the placement.
In total, Huddinge, Denmark-based Medivir issued 2.25 million new shares at SEK125 ($18.23) each to 30 international institutional investors, plus some institutions in Sweden that were not already shareholders.
That represented a 7.9 percent dilution for existing investors. More than two-thirds of the new shares were taken up by international investors. Medivir is quoted on the Nasdaq OMX Exchange in Stockholm.
"This will enable Medivir to strengthen its R&D and take a higher amount of value going forward, by doing joint ventures rather than licensing, and [allowing us to] take products further," Piir said.
Medivir announced its intention of doing the placing in March when it sought approval from shareholders, but its ability to do so rests on positive Phase IIb data for TMC 435. The product is partnered by Johnson & Johnson subsidiary Tibotec Pharmaceuticals Ltd., with Medivir retaining rights in Nordic markets.
Last month, Medivir announced positive interim data from Aspire, a Phase IIb study of TMC 435 as a once-daily therapy in 462 HCV patients who had been treated previously with pegylated interferon (peg-INF).
TMC 435, added to standard of care, increased the number of patients whose HCV levels were undetectable at 24 weeks.
Across four treatment groups, between 79 percent and 86 percent of patients were able to stop taking any therapy at 24 weeks. Patients in the study were infected with genotype 1 HCV, which is hard to treat.
The product also had positive results in a 386-subject Phase IIb study in treatment-naïve patients, which reported in July. Here, 83 percent of those treated with TMC 435 were able to stop all therapy at 24 weeks.
Those results were presented by Tibotec at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, in October.
"We witnessed enthusiasm for TMC435 at the AASLD clinical meeting, which together with positive Phase IIb Aspire results, boosts our confidence and price target, by 6 percent," noted Peter Welford, equity analyst at Jeffries in London
The shares closed at SEK120 on Dec. 3, the day the completion of the placing was announced. Welford added that Medivir is, "The European biotech best placed to benefit from broad enthusiasm for the wave of new blockbuster hepatitis C therapies reaching the market."
Building on the success of TMC 435, the company has other HCV products coming through its pipeline. "Investors are supporting Medivir in efforts to become a leading player in HCV," Piir said.
The company also intends to apply its technology to new therapeutic areas. "We are in discussion on [doing] this in a joint venture structure," Piir added.
Wednesday, December 1, 2010
"Sticking Fast To Foil Hepatitis C" article from Chemistry & Engineering News...
A deeper look on Avila Therapeutics development of new protease blockers that irreversibly inhibit the HCV protease enzyme - Chris
Biochemistry: Aiming beyond the active site of a virus's key protease yields selective blockers
Carmen Drahl
By targeting a noncatalytic cysteine, researchers have designed selective irreversible blockers of a protease enzyme essential for hepatitis C virus replication (Nat. Chem. Biol., DOI: 10.1038/nchembio.492).
The work is the first demonstration that steering clear of the active site is a viable design strategy for drugs that react to form a covalent bond to proteases, a broad class of proteins that includes many drug targets. This strategy has already proven useful for blocking other proteins such as kinases.
A team from the biotechnology company Avila Therapeutics developed the new protease blockers, which covalently bind to a cysteine in hepatitis C protease's substrate-binding site. In contrast, most other hepatitis C protease inhibitors in development reversibly bind to a catalytic amino acid common to proteases in human hosts as well as in viruses. Avila's published inhibitor structures are prototypes, but the company hopes to begin human clinical trials with optimized compounds in 2011. The team says its comprehensive structural analysis of hundreds of proteases suggests this strategy can be applied broadly.
However, it's not clear how applicable the team's strategy will be to all proteases, says Matthew S. Bogyo of Stanford University, who develops chemical tools to study the roles of proteases in disease. Nevertheless, "covalent inhibitors benefit from a long duration of action, and when used for clearing pathogens such as hepatitis C virus, they may make more sense than classical reversible inhibitors," Bogyo says. Covalent inhibitors can also make several aspects of drug development more straightforward because it's easier to monitor their target selectivity and distribution throughout the body compared with reversible inhibitors, he adds.
Biochemistry: Aiming beyond the active site of a virus's key protease yields selective blockers
Carmen Drahl
By targeting a noncatalytic cysteine, researchers have designed selective irreversible blockers of a protease enzyme essential for hepatitis C virus replication (Nat. Chem. Biol., DOI: 10.1038/nchembio.492).
The work is the first demonstration that steering clear of the active site is a viable design strategy for drugs that react to form a covalent bond to proteases, a broad class of proteins that includes many drug targets. This strategy has already proven useful for blocking other proteins such as kinases.
A team from the biotechnology company Avila Therapeutics developed the new protease blockers, which covalently bind to a cysteine in hepatitis C protease's substrate-binding site. In contrast, most other hepatitis C protease inhibitors in development reversibly bind to a catalytic amino acid common to proteases in human hosts as well as in viruses. Avila's published inhibitor structures are prototypes, but the company hopes to begin human clinical trials with optimized compounds in 2011. The team says its comprehensive structural analysis of hundreds of proteases suggests this strategy can be applied broadly.
However, it's not clear how applicable the team's strategy will be to all proteases, says Matthew S. Bogyo of Stanford University, who develops chemical tools to study the roles of proteases in disease. Nevertheless, "covalent inhibitors benefit from a long duration of action, and when used for clearing pathogens such as hepatitis C virus, they may make more sense than classical reversible inhibitors," Bogyo says. Covalent inhibitors can also make several aspects of drug development more straightforward because it's easier to monitor their target selectivity and distribution throughout the body compared with reversible inhibitors, he adds.
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