Cohort Dosing Completed in Clinical Trial of HCV Polymerase Inhibitor
Anadys Pharmaceuticals announced this month that investigators
have completed dosing for the first patient cohort in
an ongoing Phase 2 clinical trial of ANA598,
the company's experimental non-nucleoside hepatitis
C virus (HCV) polymerase inhibitor. The study is testing
2 different doses of ANA598 in combination with pegylated
interferon plus ribavirin in previously untreated genotype
1 chronic hepatitis C patients.
is an excerpt from a company press release describing the trial
Pharmaceuticals Provides Progress Update on
Phase II Study of ANA598 in Hepatitis C Patients
ANA598 dosing completed in the 200 mg bid cohort
Enrollment completed in the 400 mg bid cohort
Diego, CA -- January 22, 2010 -- Anadys Pharmaceuticals,
Inc. (Nasdaq: ANDS) today announced that ANA598 dosing has
been completed in the first dose cohort, 200 mg bid [twice
daily], in an ongoing Phase II study of ANA598 in combination
with pegylated interferon and ribavirin (SOC) in HCV patients.
Anadys expects to receive 12-week safety and antiviral response
data for the 200 mg bid cohort in the first quarter of 2010.
Anadys also announced that all patients have commenced dosing
in the second dose cohort, 400 mg bid. With patient enrollment
in this cohort completed, Anadys has accelerated the expected
timing to receive 4-week safety and antiviral response at
400 mg bid to the end of the first quarter of 2010 and continues
to expect 12-week safety and antiviral response data in
the second quarter of 2010.
"We are very pleased with the rapid progress of this
study and appreciate the commitment of everyone involved
in the trial," said Steve Worland, PhD, President and
Chief Executive Officer of Anadys. "With continuing
positive data, we hope to see ANA598 established as the
leading non-nucleoside in HCV, suitable for combination
with current standard of care as well as with other direct
antivirals currently in development."
Phase II Combination Study
Anadys recently reported positive initial antiviral response
and safety results from the 200 mg bid dose cohort based
on a planned interim analysis of data at four weeks. In
the group receiving ANA598 added to SOC, there was a steady
increase in the percentage of patients with undetectable
levels of virus from week 1 through week 4, with 56% of
patients achieving undetectable levels of virus at week
4 (defined as Rapid Virological Response or RVR), compared
to 20% of patients receiving placebo plus SOC achieving
an RVR. No patient receiving ANA598 experienced viral rebound
(defined as >1 log(10) increase from a prior measurement)
through week 4. ANA598 also demonstrated a favorable safety
profile through four weeks. There were no serious adverse
events reported and the profile of adverse events reported
was as expected for patients receiving SOC alone, with comparable
rates observed between the ANA598 and placebo arms.
In the ongoing Phase II study, treatment-naive genotype
1 patients are to receive ANA598 or placebo in combination
with Pegasys (peginterferon alfa-2a) and Copegus (ribavirin,
USP) for 12 weeks at dose levels of 200 mg or 400 mg both
given twice daily (bid), each with a loading dose of 800
mg bid on day one. After week 12, patients are to continue
receiving SOC alone. Patients who achieve undetectable levels
of virus at weeks 4 and 12 will be 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 are planned to be enrolled in this study --
with approximately 30 patients receiving ANA598 and 15 receiving
placebo at each dose level. The study is being managed by
the Duke Clinical Research Institute (DCRI) under the leadership
of John McHutchison, MD, and is being conducted at a number
of clinical sites in the United States.
ANA598 is a non-nucleoside inhibitor of the HCV RNA polymerase
and is wholly owned by Anadys. In a Phase I study in HCV
patients, ANA598 demonstrated potent antiviral activity
when dosed as monotherapy over three days. Anadys has also
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
Anadys has presented in vitro data supporting the use of
ANA598 in combination with interferon-alpha as well as with
direct antivirals currently in development. In particular,
data has shown that ANA598 is synergistic in vitro with
interferon-alpha as well as representative HCV protease
and polymerase inhibitors. In vitro combination treatment
at clinically relevant concentrations of interferon-alpha
and ANA598 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, and 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 about Anadys, see www.anadyspharma.com.
Pharmaceuticals. Anadys Pharmaceuticals Provides Progress Update
on Phase II Study of ANA598 in Hepatitis C Patients. Press release.
January 22, 2010.