Session Title: Category 13. LATE-BREAKERS
Presentation Date: Apr 15, 2010
SAFETY AND ANTIVIRAL ACTIVITY OF ANA598 IN COMBINATION WITH PEGYLATED INTERFERON α2A PLUS RIBAVIRIN IN TREATMENT-NAÏVE GENOTYPE-1 CHRONIC HCV PATIENTS
E. Lawitz1*, M. Rodriquez-Torres2, V.K. Rustgi3, T. Hassanein4, M.H. Rahimy5, C.A. Crowley5, J.L. Freddo5, A. Muir6, J. McHutchison6
1Alamo Medical Research, San Antonio, TX, 2Fundación de Investigación de Diego, Santurce, PR, 3Metropolitan Research, Fairfax, VA, 4SCTI Research Foundation, Liver Center, San Clemente, 5Anadys Pharmaceuticals, Inc, San Diego, CA, 6Duke Clinical Research Institute, Durham, NC, USA. *email@example.com
Background: ANA598 is a potent non-nucleoside inhibitor of HCV polymerase. ANA598 was well tolerated in HCV patients at 200mg, 400mg and 800mg bid for 3 days, and resulted in rapid reduction in HCV RNA (median EOT range 2.3 to 2.9log10). This study evaluates safety and antiviral activity of ANA598 with PEG-IFN and ribavirin (SOC). 12-week results for the first cohort (200mg bid) are reported here; 400mg bid cohort is in progress and will be presented.
Methods: ANA598-504 is an ongoing double-blind, placebo-controlled Phase2 study to assess safety, antiviral activity and PK of ANA598 in genotype-1 patients. Patients receive ANA598 or placebo with SOC for 12 weeks at 200mg bid or 400mg bid, both given with a loading dose of 800mg q12h on day 1. Patients who achieve undetectable virus at weeks 4 and 12 are randomized to SOC alone for 12 or 36 additional weeks.
Results: 44 patients received at least one dose in the first cohort (29 received ANA598 and 15 placebo). Four patients voluntarily withdrew from the study. One patient discontinued ANA598 and 3 patients discontinued placebo due to failure to reach a 1 log10 decline in HCV RNA by Week 4, but continued to receive SOC. Forty patients (30 1a and 10 1b) completed 12 weeks of treatment. No serious AEs were reported. The most common AEs were those associated with SOC. Occurrence of rash was similar between ANA598 (12/29, 41%) and placebo (5/15, 33%). Only one patient discontinued ANA598 due to an AE (Grade 3 rash at Week 8). All other rashes reported in ANA598-treated patients were Grade 1. Table shows a summary of antiviral activity. No patient demonstrated viral breakthrough (>1 log increase). ANA598 plasma levels also achieved steady state by Week 1.
[Table 1; * N=26 for ANA598 & 14 for Placebo]
|Patients (%) with Undetectable Virus (<15 IU/mL) by Week |
| ||Week 4 (RVR) ||Week 6 ||Week 8 ||Week 10 ||Week 12* (cEVR) |
|ANA598+SOC ||56 ||65 ||69 ||73 ||73 |
|Placebo+SOC ||20 ||27 ||47 ||54 ||71 |
Conclusions: The combination of ANA598 with SOC was well tolerated and ANA598 accelerated the rate of achieving undetectable virus in genotype-1 patients.