Patients who are stable on Hepsera, will probably not switch so I'd expect GILD to promote Viread mainly in first line HBV where Hepsera’s use is limited anyway.
Gilead Reports 72-Week Data from Phase-3 Viread Studies in HBV
[Viread for HBV is already approved in the EU and will almost certainly be approved by the FDA later this year. (The PDUFA date is 8/11/08.) GILD previously reported 48-week data from these two studies, which were the basis for the European and US submissions (#msg-24255644). The 72-week data reported here were from open-label extensions of the two phase-3 studies in which patients originally randomized to Hepsera switched to Viread. Also reported in this PR are interim data from a head-to-head study of Viread vs Truvada in first-line HBV.]
- Oral Presentations at EASL Following Recent CHMP Positive Opinion Support Viread as Potential New Treatment for Life-Threatening Liver Disease -
MILAN, Italy--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD ) today announced the presentation of detailed 72-week 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 Friday, April 25, at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL) currently taking place in Milan, Italy (April 23-27).
Studies 102 and 103 were designed to evaluate treatment with Viread over 240 weeks among patients with HBeAg-negative (presumed pre-core mutant) and HBeAg-positive chronic hepatitis B, respectively. Patients in both studies were originally randomized to receive Viread or Gilead’s Hepsera® (adefovir dipivoxil). The studies’ primary efficacy endpoints were reached at 48 weeks, at which time Viread demonstrated superior efficacy over Hepsera. After the completion of 48 weeks of randomized blinded therapy, all eligible patients were offered open-label Viread monotherapy.
The 72-week data demonstrate that the majority of patients in each study who were originally randomized to receive Viread had a virologic response below 400 copies/mL through week 72 (91 percent and 79 percent, respectively). The studies also show that all 88 Hepsera-treated patients who achieved HBV DNA levels below 400 copies/mL at week 48 maintained viral suppression after switching to Viread. Additionally, Hepsera-treated patients with HBV DNA levels above 400 copies/mL at week 48 experienced rapid viral suppression after switching to Viread in each study (94 percent and 78 percent, respectively). Viread was generally well tolerated through week 72.
“These 72-week data indicate that Viread has the potential to produce a significant and sustained effect on HBV DNA suppression,” said Patrick Marcellin, MD, PhD, Hôpital Beaujon University of Paris and the principal investigator for Study 102. “When considered alongside its well-established safety profile, including more than one million patient years of experience in HIV, I believe Viread will be an important new treatment option for patients living with chronic hepatitis B.”
Study 102
Study 102 is a multi-center, randomized, double-blind Phase III clinical trial evaluating the efficacy, safety and tolerability of Viread among patients with HBeAg-negative presumed pre-core mutant chronic hepatitis B. Study participants were either new to HBV therapy (treatment-naive), or had previous experience with lamivudine (treatment-experienced). Three hundred seventy-five patients were originally randomized in a 2:1 ratio to receive either Viread (300 mg once daily; n=250) or Hepsera (10 mg once daily; n=125) for 48 weeks. Baseline characteristics were similar between patients in both study arms. After the completion of 48 weeks of randomized blinded therapy, all eligible patients were offered open-label Viread monotherapy.
At week 72, 91 percent of patients who were originally randomized to receive Viread had a virologic response below 400 copies/mL. For Hepsera-treated patients who switched to Viread after week 48, 88 percent achieved HBV DNA levels below 400 copies/mL by week 72. Notably, through week 72, viral suppression was maintained among all patients who switched to Viread and who were previously virologically controlled with Hepsera (n=76). Additionally, rapid viral suppression to less than 400 copies/mL was achieved by week 72 in 94 percent of viremic Hepsera-treated patients who switched to Viread.
At week 72, normal alanine aminotransferases (ALT, a measure of liver damage) was observed in 79 percent of patients who were originally randomized to receive Viread and in 77 percent of Hepsera-treated patients who switched to Viread after Week 48.
Viread was generally well tolerated through week 72. In Study 102, treatment-related serious adverse events occurred in less than 1 percent of patients who were originally randomized to receive Viread and less than 1 percent of patients originally randomized to receive Hepsera. The incidence of Grade 3/4 laboratory abnormalities was comparable in each arm (14 percent versus 13 percent for Grade 3 abnormalities and 5 percent versus 2 percent for Grade 4 abnormalities). No patient had a confirmed creatinine clearance of less than 50 mL/minute.
Resistance surveillance through week 72 did not detect any tenofovir-associated mutations. Two patients exhibited loss of viral response as defined by study investigators with documented non-adherence and were evaluated via genotypic analysis. Neither developed mutations associated with Viread resistance.
Study 103
Study 103 is a multi-center, randomized, double-blind Phase III clinical trial evaluating the efficacy, safety and tolerability of Viread among treatment-naive patients with HBeAg-positive chronic hepatitis B. Two hundred sixty-six patients were originally randomized in a 2:1 ratio to receive either Viread (300 mg once daily; n=176) or Hepsera (10 mg once daily; n=90). Baseline characteristics were similar between patients in both study arms. As with Study 102, after the completion of 48 weeks of randomized blinded therapy, all eligible patients were offered open-label Viread monotherapy.
At week 72, 79 percent of patients who were originally randomized to receive Viread had a virologic response below 400 copies/mL. Among Hepsera-treated patients who switched to Viread after Week 48, 76 percent achieved HBV DNA below 400 copies/mL by week 72. Through week 72, viral suppression was maintained among all patients who switched to Viread and who were previously virologically controlled with Hepsera (n=12). Additionally, rapid viral suppression to less than 400 copies/mL was achieved by week 72 in 78 percent of viremic Hepsera-treated patients who switched to Viread after week 48.
At week 72, normal ALT levels were observed in 77 percent of patients who were originally randomized to receive Viread and 61 percent of Hepsera-treated patients who switched to Viread.
Among patients for whom seroconversion data was available through week 64, 26 percent of patients who were originally randomized to receive Viread “e” antigen seroconverted, compared to 21 percent of Hepsera-treated patients who switched to Viread. Seroconversion is defined as both the disappearance of the hepatitis B “e” antigen (HBe-antigen negative), a marker of HBV replication, and the appearance of antibodies specific for this antigen (HBe-antibody positive). In addition, 5 percent of patients who were originally randomized to receive Viread compared to zero percent of Hepsera-treated patients who switched to Viread after week 48 experienced “s” antigen (HBsAg) loss (p=0.004), which can indicate that a patient has cleared chronic hepatitis B infection.
As with Study 102, Viread was generally well tolerated. At week 72, treatment-related serious adverse events occurred in 4 percent of patients who were originally randomized to receive Viread and 7 percent of Hepsera-treated patients. The incidence of Grade 4 laboratory abnormalities was comparable in each arm (12 percent versus 11 percent). Grade 3 laboratory abnormalities, excluding ALT elevations, were 18 and 10 percent, respectively. Grade 3 ALT elevations were 15 and 10 percent, respectively, in the Viread and Hepsera arms. No patient had a confirmed creatinine clearance of less than 50 mL/minute.
The most common adverse reactions among patients receiving Viread for chronic hepatitis B in Studies 102 and 103 were headache, diarrhea, vomiting, abdominal pain, nausea, abdominal distension, flatulence, ALT increase and fatigue.
In terms of resistance surveillance, between weeks 48 and 72 no patients experienced a loss of virologic response.
Additional Oral Presentations at EASL
Three additional oral presentations, one of which features the first data to be presented from Study 106, will be highlighted at EASL. Study 106 is an ongoing, randomized, double-blind Phase II study of individuals with chronic hepatitis B infection randomized in a 1:1 ratio to receive monotherapy with Viread (n=53) or combination therapy with Truvada (emtricitabine and tenofovir disoproxil fumarate), a fixed-dose combination of Viread and Emtriva® (emtricitabine) (n=52). At study entry, participants were experiencing suboptimal virological response (HBV DNA levels greater than or equal to 1,000 copies/mL) with Hepsera therapy (for greater than 24 weeks but less than 96 weeks). The majority of study participants (58 percent) had previously been treated with lamivudine and 22 percent (n=23) had developed resistance mutations to lamivudine or Hepsera.
Through week 48, there were no statistically significant differences between the Viread and Truvada arms, with 81 percent of patients in both groups achieving HBV DNA suppression below 400 c/mL. Virologic response was independent of pre-existing lamivudine or adefovir-associated mutations. The study is ongoing and will continue to assess the best long-term treatment strategy for these difficult-to-treat patients.
Also being presented Friday are two sub-set analyses examining the efficacy of Viread in cirrhotic patients, as well as in lamivudine-experienced and treatment-naive patients. <<
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