Press Release: Idenix Reports Results from Two Phase IIb Studies
Idenix Reports Results from Two Phase IIb Studies of the Combination of Valopicitabine and Pegylated Interferon in Hepatitis C Genotype-1 Patients at the 42nd Annual Meeting of the European Association for the Study of the Liver Additional Preclinical Data Presented on Valopicitabine Combined with an Investigational Protease Inhibitor BARCELONA, Spain, April 12 -- Idenix Pharmaceuticals, Inc. today announced results from two phase IIb studies of the novel combination of valopicitabine (NM283) and pegylated interferon alfa-2a (Pegasys(R)) in both treatment-naive and treatment- experienced patients infected with the genotype-1 strain of the hepatitis C virus (HCV). These data, as well as preclinical data on the active component of valopicitabine in combination with Schering Plough's investigational protease inhibitor boceprevir (SCH 503034), will be presented at the 42nd Annual Meeting of the European Association for the Study of the Liver (EASL). Pegylated interferon alfa and ribavirin therapy, the current standard of care, is successful in treating 42 - 46 percent of treatment-naive HCV genotype-1 infected patients.(1,2) For patients who do not achieve successful treatment outcomes with pegylated interferon and ribavirin, there are currently no approved treatment options. New antiviral agents are needed to provide more treatment options for patients infected with HCV genotype-1. "We have learned a great deal about the treatment of patients with hepatitis C, as well as the safety and efficacy of valopicitabine as a result of these large phase IIb trials," said Douglas L. Mayers, executive vice president and chief medical officer of Idenix Pharmaceuticals. "We remain optimistic about the antiviral activity of the combination of valopicitabine and pegylated interferon observed in various patient populations, and believe that multi-drug combinations will play an important role in the treatment of HCV genotype-1 infected patients. We are now working to define valopicitabine's role in therapy, not only in combination with the current standard of care, but also with other investigational compounds in development." 48-Week End-of-Treatment Results in Study of Treatment-Naive Patients The first study, which was conducted at 23 sites in the United States, evaluated the safety and efficacy of various doses of valopicitabine plus pegylated interferon in 173 HCV genotype-1 infected, treatment-naive patients over 48 weeks. The primary endpoint of the study is sustained virologic response (SVR), defined as maintained viral clearance six months after treatment is stopped. At the end of the treatment period, which was 48 weeks, 53 percent (n=18/34) of patients treated with 200 mg/day valopicitabine plus pegylated interferon achieved undetectable HCV levels by the TaqMan(R) assay. "These data are encouraging," said Eric Lawitz, M.D., medical director, Alamo Medical Research. "It is important to remember that ribavirin was not used in this study. The addition of ribavirin to the combination of valopicitabine and pegylated interferon may increase on-treatment response and may help to prevent post-treatment relapse. I look forward to the results from the company's ongoing study exploring the triple combination." Through 48 weeks of treatment, 38 out of a total of 173 patients discontinued from the trial for adverse events (AEs), mostly gastrointestinal (GI)-related; of these, 3 patients were receiving the 200 mg/day dose of valopicitabine. Seven serious adverse events (SAEs) were assessed as attributable to either valopicitabine or valopicitabine and pegylated interferon during the first 48 weeks of treatment, most of which were GI- related. In this study, no valopicitabine-related GI SAEs have occurred since March 2006, when this study was amended to reduce the dose of valopicitabine administered to 200 mg/day or 400 mg/day. Final Results in Study of Treatment-Experienced Patients The second phase IIb clinical trial, which was conducted at 22 sites in the United States, evaluated various doses of valopicitabine in combination with pegylated interferon compared to pegylated interferon and ribavirin in 178 HCV genotype-1 infected, treatment-experienced patients for a treatment duration of up to 72 weeks. The primary endpoint of the study was SVR, defined as maintained viral clearance six months after treatment is stopped. The end- of-treatment response rates and post-treatment SVR rates were comparable for patients receiving valopicitabine and pegylated interferon and those receiving pegylated interferon and ribavirin. Of patients treated with valopicitabine in combination with pegylated interferon, none achieved an SVR, compared to one patient retreated with pegylated interferon and ribavirin. Of the patients enrolled in this trial, 16 percent were partial responders, meaning they achieved a greater than or equal to 2 log reduction but never cleared the virus during their prior course of pegylated interferon and ribavirin therapy, and 84 percent were prior null responders, meaning they had never achieved a 2 log reduction in virus levels. In this study, 42 percent (n=10/24) of prior partial responders treated with valopicitabine and pegylated interferon achieved PCR-negativity at the end-of-treatment, compared to 16 percent (n=19/120) of prior null responders treated with valopicitabine and pegylated interferon. "These data are significant as they underscore the difficulty in retreating patients who have failed standard of care," said Nezam Afdhal, M.D., chief of hepatology and director of the liver center, Beth Israel Deaconess Medical Center. "There was a significant antiviral response to the combination of valopicitabine plus pegylated interferon in prior partial responders which is encouraging. Based on these data, further studies are warranted to assess if the addition of ribavirin and potentially another investigational agent to this treatment regimen could offer partial responders/relapsers to prior therapy a viable treatment option." In this study, 31 out of a total of 178 patients discontinued from the trial for AEs, of which 12 were GI-related. Seven SAEs were assessed as attributable to either valopicitabine or valopicitabine and pegylated interferon during this study, most of which were GI-related. In this study, no valopicitabine-related GI SAEs occurred after March 2006, when this study was amended to reduce the dose of valopicitabine administered to 400 mg/day. Preclinical Data in Combination with an Investigational Protease Inhibitor A separate study presented at EASL evaluated the combined antiviral effect of the active component of valopicitabine, NM107, and SCH 503034, Schering Plough's investigational protease inhibitor currently in phase II trials, using cell culture replicon studies. The in vitro results demonstrated that the combination of these two agents provided additive antiviral activity compared to either agent used alone, with no cross resistance. Additionally, the combination of SCH 503034 and NM107 significantly reduced the frequency of resistant colonies, compared to each agent used alone, indicating that the combination of the two agents increased the barrier for developing resistance to either drug. Further studies are warranted to determine the clinical relevance of these findings. About Valopicitabine (NM283) Valopicitabine is an investigational HCV RNA polymerase inhibitor being evaluated in ongoing clinical trials for the treatment of hepatitis C. The most common adverse events reported in the phase IIb studies included nausea, vomiting, fatigue, diarrhea, headache, flu-like symptoms and depression. In the phase IIb studies, the occurrence of GI-related adverse events appeared to be dose dependent, and was less frequent in patients receiving 200 mg/day or 400 mg/day of valopicitabine. Idenix is developing valopicitabine in collaboration with Novartis Pharma AG. About Hepatitis C HCV infection is the most common chronic blood-borne infection in the United States.(3) The Centers for Disease Control and Prevention estimates that 4 million Americans have been infected with HCV, and 2.7 million of these carry chronic HCV infections.(4) Hepatitis C-related liver failure is the most common indication for liver transplantation in the United States.(4) As the prevalence of severe liver disease attributable to hepatitis C rises, deaths due to complications from hepatitis C infection, currently 8,000 to 10,000 per year in the United States, are increasing and are expected to triple by 2010.(5) About Idenix Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of human viral and other infectious diseases. Idenix's current focus is on the treatment of infections caused by hepatitis B virus, hepatitis C virus and human immunodeficiency virus (HIV). For further information about Idenix, please refer to http://www.idenix.com. Forward-looking Statement This press release contains "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements can be identified by the use of forward-looking terminology such as "suggest," "can," "believe," "encouraging," "provide," "expect," "will," "look forward to," or similar expressions, or by express or implied statements with respect to potential results of on-going clinical trials of NM283, approvals of NM283 by the United States or other regulatory bodies, or potential future revenues from NM283. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantees that Idenix will successfully advance NM283 or any clinic product candidate or other component of our potential pipeline in the clinic or in the regulatory process. In particular, management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to results of clinical trials, including additional data relating to the ongoing clinical trials evaluating NM283 and its other product candidates; the company's ability to obtain additional funding required to conduct its research, development and commercialization activities; the company's dependence on its collaboration with Novartis Pharma AG; the ability of the company to attract and retain qualified personnel; competition in general; and the company's ability to obtain, maintain and enforce patent and other intellectual property protection for its other product candidates and its discoveries. These and other risks which may impact management's expectations are described in greater detail under the caption "Risk Factors" in the company's annual report on Form 10-K for the year ended December 31, 2006 and filed with the Securities and Exchange Commission and other filings that the company makes with the Securities and Exchange Commission. All forward-looking statements reflect the company's expectations only as of the date of this release and should not be relied upon as reflecting the company's views, expectations or beliefs at any date subsequent to the date of this release. Idenix anticipates that subsequent events and developments may cause these views, expectations and beliefs to change. However, while Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so.