PRINCETON, N.J., July 8 /PRNewswire-FirstCall/ -- The French National Agency for Research on AIDS and Viral Hepatitis (ANRS), with the support of Pharmasset, Inc. and Gilead Sciences, Inc. , has initiated the first head-to-head study of clevudine and Viread(R) (tenofovir disoproxil fumarate) administered separately, versus their combination, for the treatment of chronic hepatitis B virus (HBV) infection in non-cirrhotic patients. The study treatments include clevudine 30mg/day, tenofovir 300mg/day or the combination of both drugs administered to 150 treatment-naive hepatitis B e-antigen negative HBV-infected patients for 96 weeks. At that time, all therapy will be discontinued, and patients will be monitored for sustained virologic response (SVR) after being off of therapy for 24 weeks, the primary endpoint of the study.
Clevudine is an oral, once-daily pyrimidine nucleoside analog that has been evaluated in 18 clinical trials in more than 800 individuals. Phase 3 studies are currently being conducted in approximately 140 global clinical sites to support the registration of clevudine in the Americas and Europe. Pharmasset licensed clevudine for these territories from Bukwang Pharm. Co., Ltd, who has received South Korean regulatory approval and is currently marketing clevudine in South Korea under the brand name Levovir.
“Clevudine’s unique mechanism of action as a non-chain terminating nucleoside analog HBV polymerase inhibitor may demonstrate additive antiviral benefit in combination with tenofovir’s recently demonstrated antiviral potency in HBV,” stated Dr. Michelle Berrey, Pharmasset’s Chief Medical Officer. “We also plan to reproduce the results from earlier studies demonstrating clevudine’s ability to provide a sustained virologic response in patients with eAg negative chronic HBV infection, as either monotherapy or in combination, offering infected individuals and their physicians an important new treatment option.”
Ongoing Registration Studies for New Drug Application (NDA)
The ongoing clevudine Phase 3 registration program includes two 48-week clinical trials designed to demonstrate the superiority of clevudine 30mg over Hepsera(R) (adefovir dipivoxil) 10mg, each administered once-daily as monotherapy. Pharmasset plans to submit the 48-week data from these studies to the FDA as the basis for the clevudine marketing approval. Please see www.clinicaltrials.gov or e-mail clinicaltrials@pharmasset.com for more information about the clevudine registration studies.
South Korean Registration Studies for Clevudine
Bukwang received marketing approval for clevudine from the South Korean FDA based on two 24-week, placebo-controlled, double-blind, randomized, multi-center South Korean Phase 3 registration trials in 337 patients. Study 301 enrolled 248 HBeAg+ patients who received clevudine 30 mg or a placebo once-daily, and Study 302 enrolled 89 HBeAg- patients who received clevudine 30 mg or a placebo once-daily. All patients were evaluated for an additional 24 weeks of follow-up care without clevudine treatment.
At 24 weeks on treatment with clevudine, 59% of HBeAg+ patients achieved undetectable HBV DNA and 92% of HBeAg- patients achieved undetectable HBV DNA. These results were statistically significant compared to placebo. In addition to the potent antiviral suppression, 16% of the HBeAg- patients who received clevudine demonstrated a sustained virologic response (SVR) 24 weeks after stopping therapy, versus 0% of the patients who had received the placebo. In Study 303, a South Korean open-label, follow-on study of clevudine, Bukwang observed similar findings. 80% of HBeAg- patients had undetectable HBV DNA 12 weeks after completing a 48-week course of therapy.
Clevudine was generally safe and well-tolerated by patients with chronic HBV. There was no meaningful difference between clevudine and placebo in the incidence of serious adverse events during treatment in Studies 301 and 302 and during follow-up except that a higher percentage of placebo-treated patients had elevated liver enzyme levels than patients treated with clevudine.
About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing and commercializing novel drugs to treat viral infections. Pharmasset’s primary focus is on the development of oral therapeutics for the treatment of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV).
Pharmasset is currently developing three product candidates. Clevudine, for the treatment of chronic HBV infection, is in Phase 3 clinical trials for registration in the Americas and Europe. Clevudine is already approved for HBV in South Korea and marketed by Bukwang Pharmaceuticals in South Korea under the brand name Levovir. R7128, an oral treatment for chronic HCV infection, is in a Phase 1/2 clinical trial through a strategic collaboration with Roche. Racivir, which is being developed for the treatment of HIV in combination with other approved HIV drugs, has completed a Phase 2 clinical trial.
Forward-Looking Statements
Pharmasset “Safe Harbor” Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release regarding our business that are not historical facts are “forward-looking statements” that involve risks and uncertainties, including without limitation the risk that Clevudine will not demonstrate any additive antiviral benefit in combination with tenofovir in the head-to-head study, the risk that Clevudine will not demonstrate superiority over Hepsera in Clevudine’s ongoing Phase 3 registration study, the risk that adverse events could cause the cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of these risks and uncertainties, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section of our Annual Report on Form 10-K for the fiscal year ended September 30, 2007 filed with the Securities and Exchange Commission entitled “Risk Factors” and discussions of potential risks and uncertainties in our subsequent filings with the Securities and Exchange Commission.
Viread and Hepsera are registered trademarks of Gilead Sciences, Inc.
CONTACT: Kurt Leutzinger, Chief Financial Officer, Pharmasset, Inc.,
+1-609-613-4110, kurt.leutzinger@pharmasset.com
Web site: http://www.pharmasset.com/
http://www.clinicaltrials.gov/
