Second Phase III Study Confirms Tenofovir (Viread) Works as Well as Adefovir (Hepsera) for Treatment of Chronic Hepatitis B

As previously reported, in early June Gilead Sciences announced data from a Phase III trial (Study 102) showing that its nucleotide analog tenofovir (Viread) was as effective as adefovir (Hepsera) for the treatment of patients with "e" antigen (HBeAg)-negative chronic hepatitis B.

On June 25, the company announced that a second Phase III trial (Study 103) demonstrated that tenofovir was also non-inferior to adefovir in patients with HBeAg-positive chronic hepatitis B.

Adefovir is currently approved as a treatment for hepatitis B. Tenofovir is approved for treatment of HIV, but not yet for HBV; it is also a component of the fixed-dose combination pills Truvada (tenofovir/emtricitabine) and Atripla (tenofovir/emtricitabine/efavirenz).

Based on the data from these 2 studies, Gilead plans to file for regulatory approval of tenofovir as a treatment for chronic hepatitis B in the U.S. and the European Union by the end of 2007.

Below is an excerpt from Gilead's press release announcing the results from Study 103:

Second Phase III Study Evaluating Gilead's Viread for the Treatment of Chronic Hepatitis B Virus Meets Primary Endpoint

Foster City, CA -- June 25, 2007 - Gilead Sciences, Inc. (Nasdaq: GILD) today announced that Study 103, a Phase III clinical trial evaluating the company's once-daily anti-HIV drug Viread (tenofovir disoproxil fumarate or tenofovir DF) 300 mg as a potential treatment for chronic hepatitis B virus (HBV) infection, met its primary efficacy endpoint. The data show that Viread is non-inferior to the company's once-daily antiviral drug Hepsera (adefovir dipivoxil) among patients with "e" antigen (HBeAg)-positive chronic hepatitis B.

The primary efficacy endpoint, the proportion of patients with a complete response at week 48, was defined by serum HBV DNA levels below 400 copies/mL and histologic improvement characterized by at least a two point reduction in the Knodell necroinflammatory score (a measure of necro-inflammation -- an inflammatory process in the liver including or leading to death of liver cells) with no concurrent worsening of fibrosis (scarring of liver tissue).

At 48 weeks, 66.5 percent of patients in the Viread arm (n=176) had a complete response compared to 12.2 percent in the Hepsera arm (n=90; p<0.001). The most commonly observed treatment-emergent adverse events of moderate intensity or higher were abdominal pain, back pain, headache, respiratory infections and transaminase elevations. The incidence of these events was comparable between the Viread and Hepsera arms of the study. In addition, the most frequently observed grade 3 or 4 laboratory abnormalities were elevations in transaminase and serum amylase and were comparable between the two arms.

Full study results will be submitted for presentation at an upcoming scientific meeting. Study 103 is the second of two Phase III pivotal studies evaluating the efficacy, safety and tolerability of Viread for the treatment of chronic hepatitis B to have met its primary efficacy endpoint. Earlier this month, the company announced that the first study (Study 102) met its primary 48-week efficacy endpoint showing that Viread is non-inferior to Hepsera among patients with HBeAg-negative/anti-HBe positive (presumed pre-core mutant) chronic hepatitis B.

"The preliminary data observed in both Phase III trials evaluating Viread as a potential treatment option for chronic hepatitis B are very encouraging," said Franck Rousseau, MD, Vice President, Clinical Research, Gilead Sciences. "We look forward to reviewing these data with regulatory authorities and are working quickly to file a New Drug Application in the United States and Marketing Authorisation Application in Europe in the fourth quarter of this year."

The active ingredient in Viread, tenofovir DF, is currently the most prescribed molecule in the United States for combination HIV therapy. Viread received approval as an anti-HIV medication from the U.S. Food and Drug Administration (FDA) in October 2001 and from the European Commission in February 2002. Viread is not approved as a treatment for chronic hepatitis B, and data from this analysis have not been reviewed by the FDA.

Study Design

Study 103 is a multi-center, randomized, double-blind Phase III clinical trial that compares the efficacy, safety and tolerability of Viread and Hepsera over 48 weeks among patients with HBeAg-positive chronic hepatitis B. Two hundred and sixty-six patients were randomized in a 2:1 ratio to receive either Viread (300 mg once daily; n=176) or Hepsera (10 mg once daily; n=90).

06/29/07

Source
Gilead Sciences. Second Phase III Study Evaluating Gilead's Viread for the Treatment of Chronic Hepatitis B Virus Meets Primary Endpoint. Press release. June 25, 2007.