76 A MOLECULAR SIGNATURE AND ALGORITHM FOR THE DIAGNOSIS AND PROGNOSIS OF HEPATOCELLULAR TUMORS

Abstract

Background: HBsAg plays a role in suppressing the immune system and may allow maintenance of chronic liver infection. REP 9AC inhibits the release of HBsAg from infected hepatocytes. In preclinical studies surface antigen seroclearance occurred after two weeks of treatment and four weeks of treatment resulted in 55% of animals achieving a durable SVR. REP 9AC is currently being evaluated in patients with chronic HBV in a proof of concept clinical trial. An updated report on interim clinical trial data will be presented. Methods: Patients were HBsAg+ with pre-treatment HBVDNA titers between 10 and 10 copies/ml and had significant liver fibrosis. Safety and virologic response (HBVDNA, HBsAg, anti-HBs) were assessed at the trial site and by confirmatory testing (HBsAg, HBeAg, anti-HBs, anti-HBe) of frozen serum samples using the ArchitectTM testing platform. Results: At the time of abstract submission, 5 of 8 patients treated have cleared serum HBsAg as early as 7 days and no later than 15 weeks following initiation of treatment at higher doses. AntiHBsAg antibodies have been observed in 7 out of 8 patients. Six, patients have achieved a 3 to 7 log reduction in their HBVDNA titers from pre-treatment levels after 7–13 weeks of treatment and three of these patients have achieved complete control of their infection after 20–27 weeks of treatment (HBVDNA−, HBsAg−, HBeAg−, antiHBs +, anti-HBe +) and are being followed off treatment. These 3 patients are currently maintaining control over their infections 14, 27 and 52 weeks after stopping treatment. Conclusions: REP 9AC can rapidly clear serum HBsAg in infected patients which appears to allow the restoration of an effective immune response, leading to the achievement of SVRs in three patients to date. These results suggest that REP 9AC may become an important new tool in the treatment of chronic hepatitis B.