FOSTER CITY, Calif. — Gilead Sciences, Inc. (Nasdaq:GILD) today announced that Study 102, a Phase III clinical trial evaluating the company’s once-daily anti-HIV drug Viread([R]) (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 study shows that Viread is non-inferior to the company’s once-daily antiviral drug Hepsera([R]) (adefovir dipivoxil) among patients with HBeAg-negative/anti-HBe positive (presumed pre-core mutant) chronic HBV infection. 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, 70.8 percent of patients in the Viread arm (n=250) had a complete response compared to 48.8 percent in the Hepsera arm (n=125; p<0.001). The most commonly observed treatment-emergent adverse events of moderate intensity or higher were abdominal pain, back pain, headache, respiratory infections, creatinine phosphokinase and transaminase elevations. The incidence of these events was comparable between the Viread and Hepsera arms of the study. In addition, the incidence of grade 3 or 4 laboratory abnormalities was comparable between the two arms. Full study results will be submitted for presentation at an upcoming scientific meeting.
"Chronic hepatitis B remains a serious disease that impacts more than one million people in the United States and an estimated 400 million people worldwide," said Franck Rousseau, MD, Vice President, Clinical Research, Gilead Sciences. "We believe Viread has the potential to be an important treatment option for patients with chronic hepatitis B and look forward to sharing detailed data from this study at a scientific conference later this year."
Study 102 is one of two Phase III pivotal studies evaluating the efficacy, safety and tolerability of Viread for the treatment of chronic hepatitis B. The second study (Study 103), a 48-week trial among patients with hepatitis B "e" antigen (HBeAg)-positive chronic hepatitis B, is expected to be complete later 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 102 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-negative/anti-HBe positive (presumed pre-core mutant) chronic hepatitis B. Three hundred and seventy-five patients were randomized in a 2:1 ratio to receive either tenofovir DF (300 mg once daily; n=250) or Hepsera (10 mg once daily; n=125).
About Viread (tenofovir disoproxil fumarate)
In the United States, Viread is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Viread should not be used in combination with the fixed-dose combination products Truvada([R]) or Atripla([TM]) because they already contain Viread.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals. Viread is not approved for the treatment of chronic hepatitis B and the safety and efficacy of Viread have not been established in patients coinfected with HBV and HIV. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued Viread. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are co-infected with HIV and HBV and discontinue Viread. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
Renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported in association with the use of Viread. It is recommended that creatinine clearance be calculated in all patients prior to initiating therapy with Viread and as clinically appropriate during therapy. Coadministration of Viread and didanosine should be undertaken with caution. Patients should be monitored closely for didanosine-associated adverse events, and didanosine should be discontinued if these occur. Patients on atazanavir and lopinavir/ritonavir plus Viread should be monitored for Viread-associated adverse events, and Viread should be discontinued if these occur. When co-administered with Viread, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg. Atazanavir without ritonavir should not be co-administered with Viread.
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