HCV Polymerase Inhibitor Setrobuvir Looks Safe and Effective in Interim Analysis

The investigational hepatitis C virus (HCV) polymerase inhibitor setrobuvir (ANA598) has demonstrated good efficacy to date in an ongoing Phase 2b trial, producing viral suppression in more than three-quarters of prior non-responders and relapsers. About 70% of treatment-naive patients were eligible for short-duration treatment based on early virological response.

Below is an edited except from a press release issued by Anadys Pharmaceuticals describing the study and its findings.

Anadys Announces Positive 12-Week Data for Setrobuvir in Phase 2b Hepatitis C Study

• Favorable Safety Data with AE Profile Comparable to Control Group
• High Barrier to Resistance Confirmed

San Diego -- October 13, 2011 -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today released interim antiviral response and safety data from an ongoing Phase IIb study of setrobuvir in combination with pegylated interferon and ribavirin (P/R) in genotype 1 hepatitis C patients. Setrobuvir is the Company’s direct-acting antiviral being developed for the treatment of chronic hepatitis C, or HCV.

"We are pleased with today’s data, which we believe demonstrate a compelling profile for setrobuvir in significantly more patients," said Steve Worland, PhD, President and CEO of Anadys. "The antiviral response in patients who had failed prior treatment is a particularly encouraging benchmark of setrobuvir’s potency and high barrier to resistance. Coupled with a favorable safety profile to date, we believe today’s data position setrobuvir as a very attractive agent to be included in future DAA combination regimens."

78% of treatment-naive patients and 76% of patients who had responded inadequately to, or relapsed after, prior treatment with P/R had undetectable virus at week 12 (cEVR) while receiving setrobuvir plus P/R, compared to 56% and 44%, respectively, for patients who received placebo plus P/R. 71% of treatment-naive patients who received setrobuvir plus P/R had undetectable virus at week 8 and met the initial response-guided criteria for shortening treatment in this study to 28 weeks from the traditional 48 weeks for treatment with P/R alone. 29% of patients who had no appreciable response to prior treatment with P/R (null responders) achieved cEVR with setrobuvir plus P/R, and the percentage of patients with undetectable virus continued to climb in this hard-to-treat population to 36% at week 18. No prior null responders received placebo plus P/R in this trial.

The viral breakthrough rate through 12 weeks on setrobuvir plus P/R was low in both treatment-naive patients (2.9%) and patients who had responded inadequately to, or relapsed after, prior treatment with P/R (3.6%). The Company believes this low incidence of viral breakthrough exhibited to date in a larger patient population further characterizes setrobuvir’s high barrier to resistance.

Setrobuvir has been generally well-tolerated in the study. Safety data for patients receiving setrobuvir plus P/R, and comparison to the control group that received placebo plus P/R, are being reported through a time period that reflects a median dosing duration of 19 weeks. The rate of discontinuing treatment in the study due to adverse events has been similar in patients receiving setrobuvir plus P/R (5.6%) or P/R alone (5.9%). The profile of adverse events has been similar between the setrobuvir and control groups, with reported adverse events being typical for patients treated with interferon and ribavirin. In the setrobuvir group, 39% of patients (84/215) developed a rash while 22% (15/68) of patients in the control group developed a rash. 98% of the rashes in the setrobuvir group were mild or moderate (grade 1 or grade 2), compared to 93% in the control group. There were no Grade 4 rashes in either group. The incidence of rash in the setrobuvir group is consistent with prior reports of rash due to interferon and ribavirin through 19 weeks of treatment.

Phase 2b Protocol Design

283 patients were dosed in this study. Patients received either setrobuvir 200 mg twice a day (bid) in combination with Pegasys (peginterferon alfa-2a) and Copegus (ribavirin, USP) (P/R)with a loading dose of setrobuvir 800 mg bid on day 1, or placebo plus P/R. Patients who had a prior null response to P/R, defined as less than a 1 log10 decline in viral load at week 4 or less than a 2 log10 decline at week 12 during prior treatment, were not randomized to receive placebo. All other patients were stratified by IL28B genotype (CC/non-CC) between setrobuvir and placebo groups. The interim antiviral response data is being reported as the proportion of patients with undetectable virus (< 15 IU/mL) using the Roche COBAS HCV TaqMan assay. The primary endpoint of the study is Sustained Virological Response 24 weeks after patients conclude all treatment, known as SVR24. In addition to the interim data released today, data through 24weeks of dosing are expected around year-end. The study is being conducted at sites in the United States, Canada, Australia and New Zealand.

Treatment-Naive Group

• 102 treatment-naive patients received setrobuvir plus P/R
• 36 treatment-naive patients received placebo plus P/R
• Treatment-naive patients who achieved undetectable levels of virus by Week 8 and maintain undetectable levels of virus are scheduled to conclude all treatment at Week 28
• For treatment-naive patients with detectable virus at Week 8, treatment with setrobuvir or placebo and P/R is scheduled to continue through Week 48

Treatment-Experienced Group (including prior null responders)

• 82 patients who were partial responders during, or relapsers after, a prior course of therapy with P/R alone received setrobuvir plus P/R
• 32 corresponding patients received placebo plus P/R
• 31 prior null responder patients received setrobuvir plus P/R
• All treatment-experienced patients are scheduled to be treated for 48 weeks

About Setrobuvir

Setrobuvir is an HCV RNA polymerase inhibitor that belongs to a chemical class referred to as non-nucleosides. Setrobuvir has a well-characterized safety database in which more than 350 subjects have received the agent to date. Setrobuvir has received Fast Track Status from the FDA for the treatment of chronic hepatitis C. Earlier this year, Anadys announced a cross-company clinical trial agreement with a large, commercial-stage biopharmaceutical company to study setrobuvir in combination with another DAA in healthy volunteers.

10/25/11

Source

Anadys Pharmaceuticals.Anadys Announces Positive 12-Week Data for Setrobuvir in Phase 2b Hepatitis C Study. Press release. October 13, 2011.