Gilead Sciences announced that the company has begun enrolling patients in its Phase III clinical program evaluating the oral nucleotide analogue (NRTI) drug tenofovir disoproxil fumarate (tenofovir DF) for the treatment of chronic hepatitis B.  Tenofovir (brand name Viread) is already FDA-approved for the treatment of HIV infection, and has been shown to have potent anti-HBV activity as well.

Two Phase III clinical trials (Studies 102 and 103) will evaluate tenofovir DF among patients with either hepatitis B “e” antigen (HBeAg)-positive chronic hepatitis B or HBeAg-negative/anti-hepatitis B “e” positive (anti-HBe positive) chronic hepatitis B. Following is an edited version of the Gilead announcement about these studies:

“Gilead has already brought to market adefovir dipivoxil (Hepsera), an important antiviral for the treatment of chronic hepatitis B,” said Norbert Bischofberger, PhD, Executive Vice President, Research and Development, Gilead Sciences. “We are pleased to now initiate our second clinical program in this therapeutic area, underscoring our dedication to and investment in exploring new treatment options for hepatitis B.”

Study Design

Studies 102 and 103 are randomized, double-blind trials that will compare the efficacy, safety and tolerability of tenofovir DF versus Gilead’s Hepsera^® (adefovir dipivoxil) over a 48-week period at more than 100 centers in 14 countries. 

Study 102 will enroll approximately 300 patients with HBeAg-negative/anti-HBe positive (presumed pre-core mutant) chronic hepatitis B, with 200 patients receiving tenofovir DF (300 mg once daily) and 100 patients receiving Hepsera (10 mg once daily). 

Study 103 is designed to enroll approximately 240 patients with HBeAg-positive chronic hepatitis B, with 160 patients receiving tenofovir DF (300 mg once daily) and 80 patients receiving Hepsera (10 mg once daily).

The primary endpoint of both trials is the proportion of patients with a complete response at week 48, defined as a serum HBV DNA level below 400 copies/mL, and improvement in liver histology scores, which is defined as at least a two-point reduction in the Knodell necroinflammatory score without worsening in fibrosis.

About Tenofovir DF

Tenofovir DF is an oral, once-daily nucleotide analogue approved by the U.S. Food and Drug Administration in October 2001 for use in combination with other antiretroviral agents for the treatment of HIV infection, and is currently in development as a treatment for chronic hepatitis B.  Tenofovir DF is believed to work by inhibiting HBV DNA polymerase, an enzyme involved in the replication of the virus in the body.

About Hepsera

Hepsera, a nucleotide analogue for the treatment of chronic hepatitis B, works by inhibiting HBV DNA polymerase, an enzyme involved in the replication of the virus in the body.

In the United States, Hepsera is indicated for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

The adverse reactions considered at least possibly related to treatment reported in 3 percent or greater of patients in the first 48 weeks in Hepsera pivotal clinical studies were asthenia, headache, abdominal pain, nausea, flatulence, diarrhea and dyspepsia. With extended treatment, mild to moderate increases in serum creatinine were observed uncommonly in patients with chronic hepatitis B and compensated liver disease treated with Hepsera for a median of 49 weeks up to a maximum of 109 weeks.

Changes in serum creatinine were observed very commonly in patients pre- and post-transplantation with lamivudine-resistant liver disease and multiple risk factors for changes in renal function who were treated with Hepsera for up to 129 weeks, with a median time on treatment of 19 and 56 weeks, respectively. Clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of treatment with antiviral therapies for hepatitis B, including Hepsera.

Special warnings and precautions for use are included in the package insert regarding monitoring of renal function, post-treatment exacerbations of hepatitis, and the occurrence of lactic acidosis and severe hepatomegaly with steatosis.  Dosing instructions for patients with underlying renal impairment and for patients co-infected with HIV are also provided in the package insert, which is available for download online at www.hepsera.com.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia.