The FINANCIAL — Gilead Sciences, Inc. (Nasdaq:GILD) on November 1 announced the presentation of two-year (96-week) data from two Phase III pivotal clinical trials, Studies 102 and 103, evaluating the safety and efficacy of once-daily Viread(R) (tenofovir disoproxil fumarate) among adult patients with chronic hepatitis B virus (HBV) infection.
These data will be presented during oral sessions at the annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2008) being held this week in San Francisco (October 31-November 4).
Studies 102 and 103 will evaluate treatment with Viread for up to eight years among patients with HBeAg-negative and HBeAg-positive chronic hepatitis B, respectively, with compensated liver disease. Patients in both studies were originally randomized to receive Viread or Hepsera(R) (adefovir dipivoxil). After the completion of 48 weeks of randomized blinded therapy, all eligible patients were rolled over to open-label Viread monotherapy.
According to Gilead, these new data show that patients who received Viread for up to 96 weeks experienced sustained suppression of HBV levels in the blood (91 percent and 78 percent for Studies 102 and 103, respectively). The studies also show that all Hepsera-treated patients whose HBV levels were suppressed at week 48 maintained viral suppression after rolling over to Viread, while Hepsera-treated patients with HBV DNA levels above 400 copies/mL at week 48 experienced significant viral suppression after rolling over to Viread. Additionally, by week 96 of Study 103, 6 percent of all patients continuing treatment in both groups experienced "s" antigen (HBsAg) loss, which contributes to resolution of chronic hepatitis B infection (HBsAg seroconversion rates were 4 percent among patients originally randomized to receive Viread and 5 percent for patients who rolled over from Hepsera).
Notably, no mutations associated with resistance to Viread were reported among patients receiving Viread monotherapy for up to 96 weeks or in Hepsera-treated patients who rolled over to Viread.
"In this study, Viread produced a significant and sustained effect over two years of treatment with no evidence of resistance, which is a substantial clinical finding," said Patrick Marcellin, MD of Hopital Beaujon in Clichy, France, the principal investigator of Study 102. "Additionally, patients in this study taking Hepsera were rolled over to Viread without new safety signals and without compromising the efficacy of anti-HBV treatment."
The U.S. Food and Drug Administration (FDA) approved Viread for chronic HBV in adults in August 2008 based on earlier (48-week) results from these studies. Viread and Hepsera are both manufactured by Gilead.
"One of the most important considerations in treating chronic hepatitis B is resistance. It is reassuring to see that no patients from either arm of the study demonstrated resistance to Viread at 96 weeks of treatment," said Jenny Heathcote, MD of the University of Toronto, Canada, the principal investigator for Study 103. "It is also notable that 6 percent of HBeAg-positive patients experienced "s" antigen loss."
Chronic HBV affects an estimated 400 million people worldwide, including two million people in the United States. Many are unaware that they are infected because the disease may not produce obvious symptoms.
One in four people with chronic hepatitis B die from complications such as cirrhosis and liver cancer. In the United States, Asian Americans are disproportionately affected: Foreign-born Asians are 100 times more likely to have the disease compared to non-Asians in the U.S. population. In September 2008, partly in response to advances in HBV therapy, the U.S. Centers for Disease Control and Prevention (CDC) published new HBV screening guidelines recommending that all individuals from Asian countries be tested for the disease.
In addition to its indication for HBV, Viread is also indicated in combination with other antiretroviral agents for the treatment of HIV infection in adults, and is currently the most-prescribed molecule in antiretroviral therapy in the United States.