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Combination Therapy with HCV Polymerase Inhibitor ANA598 Produces 12-week Sustained Response in Small Study

SUMMARY: A combination regimen consisting of Anadys Pharmaceuticals' investigational hepatitis C virus (HCV) polymerase inhibitor ANA598 plus pegylated interferon and ribavirin taken for 24 weeks produced continued viral suppression 12 weeks after completing therapy in a small Phase 2 trial of previously untreated genotype 1 patients, Anadys announced this week. Participants who stopped ANA598 and continued on pegylated interferon/ribavirin for the standard duration also showed good outcomes.


Below is an excerpt from a press release issued by Anadys describing the interim findings.

ANA598 Demonstrates SVR12 in 100% of First Group of HCV Patients Randomized to Stop All Treatment at Week 24

Benefit of ANA598 Post Therapy with IFN/RBV Persists in 6 of 6 Patients
San Diego -- July 29, 2010 -- Anadys Pharmaceuticals, Inc. (NASDAQ:ANDS) today announced that six of six patients (100%) in the ANA598 200 mg twice daily (bid) arm who were randomized to stop all treatment at Week 24 in an ongoing Phase II trial maintained undetectable levels of virus 12 weeks after stopping treatment, referred to as Sustained Virological Response 12, or SVR12.

The company also reported that all available patients from the ANA598 200 mg arm who were previously reported to have undetectable levels of virus at Week 24 and continued on pegylated interferon and ribavirin (current standard of care, or SOC) also maintained undetectable levels of virus at Week 36. In addition, all patients from the ANA598 400 mg arm who were previously reported to have undetectable levels of virus at Week 12 and continued on SOC maintained undetectable levels of virus at Week 24. ANA598, Anadys' direct-acting antiviral or DAA, is being developed to treat hepatitis C and is in an ongoing Phase II trial in combination with pegylated interferon and ribavirin.

"The SVR12 data reported today for ANA598 are highly encouraging," said Steve Worland, PhD, President and CEO of Anadys. "These data illustrate the potential for HCV patients to be successfully treated with shortened courses of treatment, reflecting the continuing benefit of ANA598 post-therapy. We believe these data, coupled with the excellent barrier to resistance demonstrated in this trial as well as the favorable safety and tolerability, confirm ANA598's position as one of the most attractive agents in Phase II HCV development today."

The six patients who stopped all treatment at Week 24 were part of an investigation of response-guided treatment duration for ANA598 in which patients who had achieved undetectable levels of virus (< 15 IU/mL) at Weeks 4 and 12 were randomized 1:1 to stop all treatment at Week 24 or Week 48. In addition to the six patients who stopped treatment at Week 24, six patients in the 200 mg bid arm are continuing to receive SOC alone through Week 48 for comparison purposes. Additionally, 14 patients from the ANA598 400 mg bid arm and 4 patients from the control arm (receiving placebo plus SOC) met the stopping criteria and have been randomized to stop all treatment at Week 24 or 48. The initial post-treatment results from these latter arms are expected later this year for those patients who stopped therapy at Week 24.

Phase II Combination Study?


In the ongoing Phase II study, approximately 90 treatment-naive genotype 1 HCV patients have received ANA598 or placebo in combination with Pegasys (peginterferon alfa-2a) and Copegus (ribavirin, USP) for 12 weeks at dose levels of 200 mg bid or 400 mg bid, each with a loading dose of 800 mg bid on day one. After week 12, patients are to continue receiving SOC. Patients who achieved undetectable levels of virus at weeks 4 and 12 were randomized to stop all treatment at week 24 or 48. The primary endpoint of the study is the proportion of patients who achieve undetectable levels of virus at week 12 (defined as complete Early Virological Response, or cEVR). Additional endpoints include safety and tolerability as well as the proportion of patients with undetectable levels of virus at week 4 (defined as Rapid Virological Response, or RVR). Patients will be followed for 24 weeks after stopping therapy to determine the rate of Sustained Virological Response, or SVR. Approximately 90 patients have been enrolled in this study - with approximately 30 patients receiving ANA598 plus SOC at each dose level and 30 patients receiving placebo plus SOC. The study is being managed by the Duke Clinical Research Institute (DCRI) and is being conducted at a number of clinical sites in the United States.

About ANA598

ANA598, a direct-acting antiviral or DAA, is a non-nucleoside inhibitor of the HCV RNA polymerase and is wholly owned by Anadys. In an ongoing Phase II study in which HCV patients received ANA598 at 200 mg bid or 400 mg bid in combination with interferon and ribavirin for twelve weeks, both dose levels showed comparable cEVR rates of 73-75% and a favorable safety profile. In a previous Phase I study, ANA598 demonstrated potent antiviral activity, including median end-of-treatment declines in viral load ranging from 2.4 to 2.9 log10 in a three day monotherapy study in treatment-naive genotype 1 patients. ANA598 has also demonstrated a very favorable resistance profile.

Anadys has completed two long-term chronic toxicology studies of ANA598 (26 weeks duration in rats and 39 weeks duration in monkeys). The No Observed Adverse Effect Level, or NOAEL, is 1000 mg/kg, the highest dose tested, in both the rat and monkey. The completed toxicology studies support the ongoing Phase II clinical study as well as future clinical studies of longer duration.

Anadys has presented in vitro data supporting the use of ANA598 in combination with interferon-alpha as well as with other anti-HCV agents currently in development that act through diverse mechanisms. In particular, data has shown that ANA598 is synergistic in vitro with interferon-alpha as well as representative HCV protease inhibitors, polymerase inhibitors, NS5A inhibitors and cyclophilin inhibitors. In vitro combination treatment at clinically relevant concentrations of ANA598 with interferon-alpha as well as DAAs from multiple classes results in clearance of HCV RNA from cells rather than selection of resistant isolates. Furthermore, ANA598 retains full activity in vitro against mutations conferring resistance to protease inhibitors, nucleoside polymerase inhibitors and non-nucleoside polymerase inhibitors that act at binding sites distinct from that of ANA598, while protease and nucleoside polymerase inhibitors retain full activity in vitro against mutations conferring resistance to ANA598.

ANA598 has received Fast Track Status from the FDA for the treatment of chronic hepatitis C.

For more information, see www.anadyspharma.com.

8/3/10

Source
Anadys Pharmaceuticals, Inc. ANA598 Demonstrates SVR12 in 100% of First Group of HCV Patients Randomized to Stop All Treatment at Week 24. Press release. July 29, 2010.


 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


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