Valopicitabine Combined with Standard of Care Cleared Hepatitis C Virus in 72% of Patients Who Completed 12 Weeks of Treatment in a Phase II Trial
CAMBRIDGE, Mass., June 12 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc. today announced results from a phase II study designed to evaluate triple combination therapy, consisting of valopicitabine (NM283), Idenix's lead drug candidate for the treatment of hepatitis C, pegylated interferon and ribavirin compared to pegylated interferon and ribavirin, the current standard of care, in patients infected with the genotype-1 strain of the hepatitis C virus (HCV). This study demonstrated no pharmacokinetic or pharmacodynamic drug-drug interaction between valopicitabine and ribavirin. The triple combination showed consistently higher rates of HCV PCR-negativity, defined as serum HCV RNA levels below 20 copies/mL, compared to the standard of care at every point analyzed in this study. Additionally, the tolerability of the triple combination was satisfactory, with only three discontinuations from the study.
"I am very encouraged to observe this degree of viral clearance coupled with a very low rate of discontinuations in patients treated with the triple combination of valopicitabine, pegylated-interferon and ribavirin in this study," said Dr. Fred Poordad, Chief of Hepatology and Liver Transplantation, Cedars Sinai Medical Center, and an investigator in this study. "These data represent an important achievement in the development of novel HCV combination therapy."
Study Design and Results
The three-arm, partially blinded, randomized study enrolled 117 treatment- naive, HCV genotype-1 infected patients at approximately 20 centers in the United States. Patients in arm A (n=39) received 200 mg/day of valopicitabine and pegylated interferon alpha 2a; patients in arm B (n=39) received 200 mg/day of valopicitabine, weight-based dosing of ribavirin, and pegylated interferon alpha 2a; and patients in arm C (n=39) received placebo, weight- based dosing of ribavirin and pegylated interferon alpha 2a. For all patients in this study there was a seven day lead-in period, where patients received either valopicitabine or placebo alone; the additional components of each arm's therapeutic regimen were administered beginning on day eight.
The primary endpoint of the study was to assess pharmacokinetic and pharmacodynamic drug-drug interaction between valopicitabine and ribavirin after 36 days of treatment. Drug levels for both NM107 (the active form of valopicitabine) and ribavirin when administered alone or together were within the range of 80 to 125 percent, indicating the lack of an interaction. At day 36, 23 percent of patients treated with triple combination therapy (arm B) were HCV PCR-negative per protocol, compared to 11 percent of patients treated with the standard of care (arm C) and 14 percent of patients treated with valopicitabine and pegylated interferon (arm A). These findings demonstrated no pharmacokinetic or pharmacodynamic drug-drug interaction between valopicitabine and ribavirin.
The key secondary endpoints for the study were antiviral activity, safety and tolerability at 12 weeks. Of patients that completed 12 weeks of therapy, 72.2 percent of patients treated with triple combination therapy (arm B) achieved HCV PCR-negativity, compared to 61.5 percent of patients treated with the standard of care (arm C). There were three discontinuations from the study, all due to adverse events (AEs), one of which was attributed by the clinical investigator to valopicitabine-related gastrointestinal toxicity. The two other AEs, including a serious adverse event (SAE), were attributed by the clinical investigators to pegylated interferon or pegylated interferon/ribavirin. All of the discontinuations occurred in the triple combination arm (arm B).
At the end of 12 weeks, patients were permitted to roll over to pegylated interferon plus ribavirin for up to 48 weeks of total treatment; all eligible patients elected to do so.
"These results support our hypothesis that valopicitabine can be administered in combination with pegylated interferon and ribavirin," said Douglas Mayers, M.D., executive vice president and chief medical officer of Idenix Pharmaceuticals. "We are very pleased with the viral kinetics and HCV RNA clearance rates observed in patients treated with triple combination therapy in this study and look forward to further development of this combination."
About Valopicitabine
Valopicitabine is an investigational nucleoside polymerase inhibitor being evaluated in ongoing clinical trials for the treatment of hepatitis C. The most common adverse events reported in valopicitabine clinical trials to date include nausea, vomiting, fatigue, diarrhea, headache, flu-like symptoms and depression. 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.(1) 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.(2) Hepatitis C-related liver failure is the most common indication for liver transplantation in the United States.(2) 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.(3)
Conference Call Information
Idenix will hold a conference call today at 8:30 a.m. EDT. To access the call please dial (800) 774-5358 U.S./Canada or (706) 758-9475 International and enter passcode 3143678 or to listen to a live webcast of the call, go to "Calendar of Events" in the Idenix Investor Center at http://www.idenix.com/. Please log in approximately 10 minutes before the call to ensure a timely connection. A replay of the conference call and webcast will be available until June 26, 2007. To access the replay, please dial (800) 642-1687 U.S./Canada or (706) 645-9291 International and enter the passcode 3143678.
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 HIV. For further information about Idenix, please refer to http://www.idenix.com/.
Forward-looking Statements
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 "will," "can be," "expect," "anticipates," "advance," "significant achievement," "pending," "encouraging," "believe," or similar expressions and implied statements with respect to the regulatory success of valopicitabine or the Idenix clinical development program in hepatitis C, or any potential pipeline candidates and expectations with respect to the size of the market for Hepatitis C. 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. In particular, management's expectations could be affected by unexpected regulatory actions or delays; results of clinical trials, including additional data relating to the ongoing or future clinical trials evaluating its 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; the company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries and the Company's ability to accurately assess the market. 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, the Company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2007 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.
(1) Center For Disease Control National Prevention Strategy.
(2) Center for Disease Control. Hepatitis C Fact Sheet accessed online at http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm.
(3) Davis, G. et al., Projecting Future Complications of Chronic Hepatitis C in the United States. Liver Transplantation, April 2003.
Idenix Pharmaceuticals' Contacts: Media: Teri Dahlman (617) 995-9905 Investors: Amy Sullivan (617) 995-9838 Idenix Pharmaceuticals, Inc.
CONTACT: Media, Teri Dahlman +1-617-995-9905, or Investors, Amy
Sullivan, +1-617-995-9838, both of Idenix Pharmaceuticals, Inc.
Web site: http://www.idenix.com/
http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm