SAN DIEGO, Dec. 17 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced preliminary results from a planned interim analysis of data at four weeks for the first dose cohort, 200 mg bid, in an ongoing Phase II study of ANA598 in combination with pegylated interferon and ribavirin (SOC) in HCV patients. 56% of patients receiving ANA598 plus SOC achieved undetectable levels of virus (<15 IU/ml) at week 4, known as Rapid Virological Response or RVR, compared to 20% of patients receiving placebo plus SOC.
ANA598 was well tolerated through four weeks, with no serious adverse events reported. An independent Data Monitoring Committee (DMC) has endorsed escalating to the second dose level, 400 mg bid, and this cohort is now open for enrollment. Anadys expects to initiate dosing in this cohort in January 2010.
"We are very pleased with the 4-week antiviral response and safety for this first dose cohort," said Steve Worland, Ph.D., President and CEO. "We look forward to the upcoming 12-week data, including antiviral response known as cEVR, for the 200 mg bid cohort in the first quarter of 2010 as well as RVR and cEVR data for the 400 mg bid cohort in the second quarter of 2010. With this additional data and results of subsequent trials, 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."
"This first Phase II data clearly demonstrates the ability of ANA598 to improve antiviral response at week 4 above what is seen with current standard of care alone," said James L. Freddo, M.D., Senior Vice President, Drug Development and Chief Medical Officer. "The RVR rate combined with a good safety and tolerability profile to date is encouraging for the prospects of ANA598 contributing to improved long-term treatment outcomes as measured by SVR."
In the ongoing Phase II study, patients are to receive ANA598 or placebo, added to SOC, for 12 weeks, after which they are to continue receiving SOC alone for 12 or 36 additional weeks. The results announced today are from a scheduled interim analysis following four weeks of dosing in the first of two planned dose cohorts. 44 patients in the first cohort (34 genotype 1a and 10 genotype 1b) received at least one dose of study medications, 29 receiving ANA598 and 15 receiving placebo. Two patients who withdrew consent during the first week of dosing for reasons unrelated to ANA598 are excluded from the analysis of antiviral response but included in the safety database. Reported antiviral response data is as of week 4. Reported safety data is as of an interim analysis date which was reached shortly after the last enrolled patient completed four weeks of dosing, and includes information through week 4 for all patients plus information subsequent to week 4 for those patients who had earlier enrollment dates.
Preliminary Antiviral Response Assessment total genotype 1a genotype 1b patients patients patients ANA598 Placebo ANA598 Placebo ANA598 Placebo +SOC +SOC +SOC +SOC +SOC +SOC --------------------------------------------------------- RVR --- Percentage of Patients with Undetectable 56% 20% 50% 17% 71% 33% HCV RNA (15/27) (3/15) (10/20) (2/12) (5/7) (1/3) (<15 IU/ml) at Week 4 VIRAL LOAD CHANGE ---------- Mean Decline in HCV RNA (log10 IU/ml) at Week 4 4.1 2.7 4.2 2.4 3.7 3.9
No patient experienced viral rebound (defined as >1 log10 increase from a prior measurement) through week 4. In accordance with the study protocol, four patients (three genotype 1a patients receiving placebo plus SOC and one genotype 1b patient receiving ANA598 plus SOC) discontinued either ANA598 or placebo at week 4 due to failing to reach at least 1 log10 viral load decline.
Preliminary Safety Assessment
Safety and tolerability from the interim analysis appeared similar between the active and placebo arms, with reported adverse events generally typical for interferon and ribavirin, although conclusions regarding longer-term safety and tolerability cannot be made until additional results over longer duration from this trial and future clinical trials in more patients are known. There were no discontinuations due to adverse events. Eight patients reported rash through the interim analysis date, seven mild and one moderate. For the six of twenty-nine patients (21%) receiving ANA598 plus SOC who reported rash, all cases were mild. For the two of fifteen patients (13%) receiving placebo plus SOC who reported rash, one case was mild and one case was moderate. There were no clinically meaningful changes in safety laboratory values and no changes in safety monitoring were recommended by the DMC in association with escalation to 400 mg bid.
Phase II Combination Study
In the ongoing Phase II study, treatment-naïve 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. An independent DMC is responsible for reviewing the safety data in the trial and has endorsed escalating to the second dose level of 400 mg bid. This cohort is now open for enrollment and Anadys expects to initiate dosing in January 2010.
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, 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.
Conference Call Webcast and Slides
Anadys will host a conference call today, December 17, 2009 at 8:30 a.m. Eastern Standard Time (5:30 a.m. Pacific Standard Time) to discuss the 4-week results from the first cohort of the ongoing Phase II clinical trial of ANA598 in combination with SOC. 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 75270153. The webcast and telephone replay will be available through December 31, 2009.
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 expected timing for enrolling the next cohort in the ANA598 Phase II study and for receiving 12 week data from the 200 mg bid cohort and 4 and 12 week data from the 400 mg bid cohort; (ii) the prospects of ANA598 being able to contribute to long-term treatment outcome as measured by SVR and the hope that ANA598 will be established as the leading non-nucleoside in HCV, suitable for combination with current SOC as well as with other direct antivirals currently in development; (iii) the ability for patients to achieve EVR and SVR in the ANA598 Phase II study; and (iv) assessments of the safety and tolerability profile of ANA598 based on the interim 4 week analysis. 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.
|SOURCE Anadys Pharmaceuticals, Inc.|
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