Oct. 31, 2009 (Business Wire) -- Gilead Sciences, Inc. (Nasdaq:GILD) today announced the presentation of three-year (144-week) open label data from two pivotal Phase III clinical trials, Studies 102 and 103, evaluating the safety and efficacy of once-daily Viread^® (tenofovir disoproxil fumarate) among adult patients with chronic hepatitis B virus (HBV) infection. These data will be presented at the annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2009) being held this week in Boston, October 30-November 3.

These new data show that the majority of patients who received Viread for up to 144 weeks experienced sustained suppression of HBV DNA levels in the blood to below 400 copies/mL (87 percent in Study 102 and 71 percent in Study 103). Additionally, cumulatively over 144 weeks, 8 percent of all patients in Study 103 (HBeAg-positive) experienced “s” antigen (HBsAg) loss, which can contribute to resolution of chronic hepatitis B infection. Notably, no mutations associated with resistance to Viread developed in any patients up to 144 weeks of treatment.

“The development of resistance is a significant challenge for practitioners treating patients with chronic hepatitis B,” said Patrick Marcellin, MD, of Hôpital Beaujon in Clichy, France, and the principal investigator of Study 102. “The robust and comprehensive resistance surveillance in these studies provides important information for the medical community and shows that Viread offers a high barrier to resistance.”

Clinical practice guidelines recommending Viread as a first-line therapy for the treatment of chronic hepatitis B were issued earlier this year by both the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. The U.S. Food and Drug Administration (FDA) approved Viread for chronic hepatitis B in adults in 2008 based on earlier (48-week) results from Studies 102 and 103, and recently approved the inclusion of 96-week data in the product’s label.

“These data underscore the rationale for Viread’s position as a recommended first-line therapy for chronic hepatitis B infection,” said Jenny Heathcote, MD, of the University of Toronto, Canada, and the principal investigator for Study 103. “In particular, the loss of the hepatitis B ‘s’ antigen in 8 percent of patients, which is associated with resolution of HBV infection, is significant from a clinical perspective.”

Nine additional presentations examining the efficacy of Viread across a variety of patient populations, including treatment-experienced patients, patients new to therapy, patients of Asian descent, pregnant women and patients with decompensated liver disease, also will be presented during The Liver Meeting.

About Studies 102 and 103

Studies 102 and 103 were multi-center, randomized, double-blind Phase III clinical trials comparing Viread to Hepsera^® (adefovir dipivoxil) among HBeAg-negative presumed pre-core mutant (n=375) and HBeAg-positive (n=266) chronic hepatitis B patients with compensated liver disease, respectively. The majority of patients were treatment-naïve upon study initiation, although some patients were lamivudine-experienced.

Patients originally randomized to Hepsera in both studies rolled over to open-label Viread (n=196) at week 48, while patients originally randomized to Viread continued open-label Viread treatment (n=389). After 72 weeks, patients with confirmed viremia (HBV DNA levels at or above 400 copies/mL on two consecutive visits) had the option of adding emtricitabine treatment by substituting Truvada^® (emtricitabine and tenofovir disoproxil fumarate) for Viread. By 144 weeks, 87 percent of patients remained in Study 102 (n=328) and 80 percent of patients remained in Study 103 (n=214).

Study 102 Results (Poster Presentation #481)

HBeAg-negative patients

A long-term evaluation algorithm through 144 weeks showed that 87 percent of patients achieved virologic suppression (HBV DNA levels below 400 copies/mL), and similar efficacy was observed between patients who received Viread monotherapy throughout (206/238, 87 percent) compared to those who initially received Hepsera and then rolled over to Viread (107/121, 88 percent).

Three patients receiving Viread had HBV DNA of 400 copies/mL or more at week 144, and one additional viremic patient discontinued Viread during year three. Three patients in Study 102 added emtricitabine treatment at or after week 72 due to confirmed viremia, and all three achieved HBV DNA levels below 400 copies/mL at week 144.

Levels of alanine aminotransferase (ALT, an enzyme that serves as a measure of liver damage), which had been high at baseline, remained at normal levels through 144 weeks of treatment (overall mean ALT value of 33 U/L).

Viread was well tolerated by study subjects during open-label treatment through 144 weeks. The incidence of serious adverse events considered drug-related was low, with one event (mild renal impairment) reported in the Viread group and none reported in the Hepsera-to-Viread group. The incidence of grade 3-4 laboratory abnormalities was similar between groups; 14 percent for Viread and 15 percent in the Hepsera-to-Viread group. During the study, three patients on Viread discontinued treatment due to adverse events (hepatocellular carcinoma, dizziness/fatigue/lack of concentration and septic shock). No patients experienced a confirmed 0.5 mg/dL increase in serum creatinine or a decrease in creatinine clearance to less than 50 mL/min. There were three deaths during open-label treatment, but the causes (nasopharyngeal cancer, metastatic liver cancer and cervical cancer) were not considered related to study drug.

No resistance to Viread developed among patients who received Viread for up to three years.