ANA598 Demonstrates 73% cEVR in Combination With Interferon and Ribavirin
No Viral Rebound Observed During 12 Weeks of ANA598 Dosing Positive Safety Data with AE Profile Comparable to Control Group Company to Review Data During Q4 Conference Call at 5:00 PM EST Today
SAN DIEGO, Feb. 24 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (NASDAQ:ANDS) today announced preliminary results from an ongoing Phase II study demonstrating that 73% of hepatitis C patients treated with 200 mg ANA598 twice daily in combination with pegylated interferon and ribavirin (SOC) achieved undetectable levels of virus (<15 iu>
No patient experienced viral rebound on ANA598. ANA598 was well
tolerated through twelve weeks, with no serious adverse events
reported and a profile of adverse events in the ANA598 group
comparable to the group receiving SOC alone.
"The 73% cEVR demonstrated by ANA598 is comparable to the most
advanced protease inhibitors currently in development for HCV,"
said Steve Worland, Ph.D., President and CEO of Anadys. "The
durability of antiviral response through twelve weeks reflects
ANA598's potency and long plasma half-life and suggests that
resistance is unlikely to be a challenge to the use of ANA598 in
appropriate combinations. Coupled with a very favorable safety
profile to date, these results position ANA598 as an attractive
candidate to advance in development, especially in combination with
other direct antivirals."
Preliminary Antiviral Response Assessment
Proportion of Patients with Undetectable Levels of Virus
(<15 iu>
*At week 12, N=26 for the ANA598 group and 14 for the placebo
group. One patient receiving ANA598 who had undetectable levels of
virus at last measurement (week 4) and one patient receiving
placebo who had a viral load of 150,000 IU/mL at last measurement
(week 10) became unavailable and are excluded from weeks subsequent
to their last measurement. The placebo values represent
approximately half the overall placebo group, with the remainder of
the placebo group being dosed presently, concurrently with patients
receiving ANA598 400 mg bid.
ANA598 demonstrated comparable potency against genotypes 1a and
1b at twelve weeks, with cEVR rates of 74% and 71% respectively. No
patient receiving ANA598 experienced viral rebound (defined as
>1 log10 increase from a prior measurement) through week 12 and
all patients who achieved undetectable levels of virus at any time
during the 12 week period remained at undetectable levels at week
12.
Preliminary Safety Assessment
ANA598 at 200 mg given twice daily (bid) demonstrated a
favorable safety and tolerability profile through 12 weeks,
although conclusions regarding safety and tolerability cannot be
made until additional results in more patients and potentially over
longer duration are known. The incidence of all adverse events was
similar between the active and placebo groups, with reported
adverse events being typical for patients treated with interferon
and ribavirin. There were no serious adverse events reported. The
incidence of rash was comparable between groups and consistent with
historical reports of rash rates due to interferon and ribavirin.
In the ANA598 group 41% of patients (12/29) developed a rash while
33% (5/15) of patients in the placebo group developed a rash.
Eleven of the twelve instances of rash in the ANA598 group were
mild. One patient in the ANA598 group experienced a grade 3 rash
which began resolving rapidly upon stopping all study medication.
Per protocol, this patient resumed interferon/ribavirin alone and
continued in the study. The five instances of rash in the placebo
group were mild. 44 patients in the first cohort received at least
one dose of study medications and are included in the safety
database. Safety information for patients receiving placebo
represents approximately half the overall placebo group, with the
remainder of the placebo group being dosed presently, concurrently
with patients receiving ANA598 400 mg bid.
Phase II Combination Study
In December 2009, Anadys 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 log10 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.
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, M.D. and is being
conducted at a number of clinical sites in the United States.
About ANA598
ANA598 is a non-nucleoside inhibitor of the HCV RNA polymerase
and is wholly owned by Anadys. Anadys has completed three Phase I
clinical studies of ANA598 that have demonstrated potent antiviral
activity and good tolerability. In a monotherapy study in
treatment-naïve genotype 1 patients, treatment with ANA598 for
three days led to median end-of-treatment declines in viral load
ranging from 2.4 to 2.9 log10 in three separate dose groups. No
patient at any dose level showed evidence of viral rebound while on
ANA598, and there were no serious adverse events. Those patients
from the monotherapy study who subsequently received pegylated
interferon and ribavirin all exhibited further viral load decline,
demonstrating that viral variants revealed by brief treatment with
ANA598 remain susceptible to current SOC, consistent with prior in
vitro results.
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 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, 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.
Conference Call Webcast and Slides
Anadys will hold a conference call and webcast today, Wednesday,
February 24, 2010 at 5:00 p.m. Eastern Standard Time to discuss its
fourth quarter and year end 2009 financial results and to discuss
the 12 week safety and antiviral response data for the 200 mg bid
cohort in the ongoing Phase II combination trial. A live webcast of
the call, including accompanying slides, will be available online
at www.anadyspharma.com. A telephone replay with slides will also
be available approximately one hour after completion of the call.
To access the telephone replay, dial 888-286-8010 (domestic) or
617-801-6888 (international), passcode 92658014. The webcast and
telephone replay will be available through March 10, 2010.
Safe Harbor Statement
Statements in this press release that are not strictly
historical in nature constitute "forward-looking statements." Such
statements include, but are not limited to, references to (i) the
belief that the durability of antiviral response through twelve
weeks reflects ANA598's potency and long plasma half-life and
suggests that resistance is unlikely to be a challenge to the use
of ANA598 in appropriate combinations; (ii) assessments of the
safety and tolerability profile of ANA598 based on the 200 mg bid
12 week results; (iii) future development activities with ANA598,
including combination trials with other direct antivirals; and (iv)
the ability for patients to achieve a SVR in the ANA598 study. Such
forward-looking statements involve known and unknown risks,
uncertainties and other factors, which may cause Anadys' actual
results to be materially different from historical results or from
any results expressed or implied by such forward-looking
statements. For example, the results of preclinical and early
clinical studies may not be predictive of future results, and
Anadys cannot provide any assurances that ANA598 will not have
unforeseen safety issues or will continue to have favorable results
as the Phase II trial progresses. In addition, Anadys' results may
be affected by competition from other biotechnology and
pharmaceutical companies, its effectiveness at managing its
financial resources, its ability to enter into transactions around
its product candidates, its ability to successfully develop and
market products, difficulties or delays in its preclinical studies
or clinical trials, difficulties or delays in manufacturing its
clinical trials materials, the scope and validity of patent
protection for its products, regulatory developments and its
ability to obtain additional funding to support its operations.
Risk factors that may cause actual results to differ are more fully
discussed in Anadys' SEC filings, including Anadys' Form 10-K for
the year ended December 31, 2008 and Anadys' Form 10-Q for the
quarter ended September 30, 2009. All forward-looking statements
are qualified in their entirety by this cautionary statement.
Anadys is providing this information as of this date and does not
undertake any obligation to update any forward-looking statements
contained in this document as a result of new information, future
events or otherwise.
Pegasys® and Copegus® are registered trademarks of
Hoffman-La Roche Inc.
Source: Anadys Pharmaceuticals,
Inc.
CONTACT: Investors, Amy Conrad of Anadys Pharmaceuticals,
Inc.,
+1-858-530-3607, aconrad@anadysphgroupa.com;
or Media, Ian Stone,
ian.stone@russopartnersllc.com,
or David Schull,
david.schull@russopartnersllc.com,
both of Russo Partners, LLC,
+1-619-528-2220, for Anadys Pharmaceuticals, Inc.
Web Site: http://www.anadyspharma.com/
Posted: February 2010
