Below is an excerpt from a press release issued by Anadys
describing the interim findings.
Demonstrates SVR12 in 100% of First Group of HCV Patients Randomized
to Stop All Treatment at Week 24
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
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.
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
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
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.
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.