Biotech Values

[DewDiligence]

ANDS is proceeding with a phase-2 ANA598 combination study,
but it will be on the company’s own dime insofar as the severe
rash seen in the ANA598 monotherapy study evidently scared
off prospective partners (#msg-37263272). As ANDS said on
a CC in June, the combination study will consist of 200mg BID
and 400mg BID cohorts, and each arm will have a first-day loading
dose of 800mg BID. Although not stated in this PR, ANDS confirmed
on today’s CC that no patients will be dosed in the 400mg arm
until patients in the 200mg arm have been evaluated for rash
and other AE’s. This implies that the FDA is indeed concerned about
the severe rash seen in the monotherapy study.

(The actual trial design differs in one respect from what ANDS had
discussed on its CC in June: Following 12 weeks of ANA598+SoC,
patients who had RVR and EVR will be randomized a second time
to receive either 12 weeks or 36 weeks of SoC alone [i.e. 24 or 48
weeks of total therapy]. In the prior guidance, ANDS said the
treatment following 12 weeks of combination therapy would be
left to the clinicians’ discretion.)

Is ANA598 now a serious drug candidate after all? Maybe.
To attract a partner, ANDS will IMO have to show unusually
strong and clean data in the combination study to erase the
stain from the monotherapy study and ANDS’ dismal overall
track record in drug development.

http://finance.yahoo.com/news/Anadys-Pharmaceuticals-prnews-1602708947.html?x=0&.v=1

›Anadys Pharmaceuticals Receives FDA Clearance of Phase II Protocol to Study ANA598 in Combination With Interferon-Alpha and Ribavirin in HCV Patients

ANA598 To Be Dosed for 12 Weeks in Triple Combination

Thursday July 30, 2009, 4:05 pm EDT

SAN DIEGO, July 30 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS ) today announced finalization of the protocol for the Company's Phase II trial of ANA598 in combination with pegylated interferon-alpha and ribavirin in hepatitis C patients. Allowance of the protocol has been received from the United States Food and Drug Administration (FDA), and patient dosing is expected to commence within the next several weeks.

In the Phase II study, naive genotype 1 patients will receive ANA598 or placebo in combination with Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin, USP) (a current standard of care, or SOC) for 12 weeks at dose levels of 200 mg or 400 mg twice daily (bid), each with a loading dose of 800 mg bid on day one. After week 12, patients will continue to receive SOC. Patients who achieve undetectable levels of virus at weeks 4 and 12 [i.e. those who achieve RVR and EVR, also known as a “durable RVR” or a “complete EVR”] will be randomized to stop all treatment at week 24 or 48. The primary endpoint of the study is the proportion of patients with undetectable 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 virus at week 4 (defined as Rapid Virological Response, or RVR), weeks 24 and 48, and 24 weeks after stopping all treatment (defined as Sustained Virological Response, or SVR).

Ninety patients are planned to be enrolled in this study - thirty patients receiving ANA598 and fifteen receiving placebo at each dose level. The study will be conducted at a number of clinical sites in the United States. Anadys expects to receive 28-day safety and response (RVR) data from the 200 mg dose level by year-end [because patients in the 400mg arm don’t start treatment until patients in the 200mg arm have been valuated for rash] and additional on-treatment safety and response data from both cohorts during the first two quarters of 2010.

"ANA598 has demonstrated potent antiviral activity and good tolerability as a single agent in Phase I, as well as preclinical properties indicative of likely synergy when used clinically in combination regimens," said Steve Worland, Ph.D., President and CEO of Anadys. "We are now in a position to demonstrate the value of ANA598 when used in combination in a Phase II trial to treat hepatitis C patients. This trial incorporates several attractive features designed to further enhance the competitive position of ANA598, including twelve weeks of triple combination treatment and a randomized exploration of shortening the overall duration of HCV therapy in conjunction with ANA598 treatment."

About ANA598

ANA598 is a non-nucleoside inhibitor of the HCV RNA polymerase. Anadys has completed three Phase I clinical studies of ANA598 that have demonstrated potent antiviral activity and good tolerability. In a monotherapy study in naive genotype 1 patients, treatment with ANA598 for three days led to median 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.

Anadys has completed dosing in two long-term chronic toxicology studies of ANA598 (26 weeks duration in rats and 39 weeks duration in monkeys). At the 13-week interim, the toxicology profile of ANA598 in both species was very favorable. A preliminary assessment of the results from the 26-week study in rats indicates a similar profile to that seen in rats at 13 weeks, in which the only adverse finding was a marginal decrease in the rate of weight gain in females at 1000 mg/kg, the highest dose tested. Complete results from both studies, including 39-week data from the monkey study, are expected at the end of the third quarter 2009.

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. 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 against mutations conferring resistance to ANA598.

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

About Anadys

Anadys Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to improving patient care by developing novel medicines for the treatment of hepatitis C. The Company believes hepatitis C represents a large unmet medical need in which meaningful improvements in treatment outcomes may be attainable with the introduction of new medicines. The Company is developing ANA598, a non-nucleoside polymerase inhibitor for the treatment of hepatitis C. The Company has also investigated the potential of ANA773, an oral, small-molecule inducer of endogenous interferons that acts via the Toll-like receptor 7, or TLR7, pathway in hepatitis C.‹