Preliminary Evidence of Rapid HBsAg Seroconversion in Patients with Chronic Hepatitis B (CHB) Treated with a DNA-based Amphipathic Polymer
Mamun Al-Mahtab1, Michel Bazinet2, Andrew Vaillant2 1Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, 2REPLICor Inc, Laval, Canada
Background: REP9AC is a DNA-based amphipathic polymer whose antiviral activity is linked to targeting viral glycoproteins important for viral entry and/or release. The preclinical evaluation of 28 days of REP 9AC therapy in ducks persistently infected with DHBV demonstrated rapid clearance of DHBV DNA, DHBsAg and rapid appearance of anti-DHBs antibodies in 55% of ducks whose blood had no detectable evidence of DHBV infection 16 weeks after cessation of REP 9AC therapy. The ability of REP 9AC to treat human patients with CHB is currently being evaluated in a proof of concept trial. Methods: Patients with CHB were subjected to REP9AC therapy administered by slow continuous infusion. Safety and virologic response (HBV DNA, HBsAg, anti-HBs) were assessed weekly, either at the trial site or by confirmatory testing (HBsAg, HBeAg, anti-HBs, anti-HBe) of frozen serum samples at a separate location using the ArchitectTM testing platform. Results: Interim data has shown that all patients treated to date have cleared HBsAg and developed protective immunity. Clearance of HBsAg and development of protective levels of anti-HBs occurred as early as 7 days following initiation of treatment at higher doses. At the time of abstract submission, one patient has already exhibited clear signs of a sustained virologic response (HBV DNA -, HBsAg -, HBeAg -, anti-HBs +, anti-HBe +) for 8 continuous weeks off treatment after receiving only 23 weeks of treatment with REP9AC. Conclusions: These results demonstrate that amphipathic polymers are effective in rapidly reducing HBsAg levels in CHB patients which allows patients to seroconvert. The rapid appearance of anti-HBs and anti-HBe antibodies in these patients, the best predictors of SVR in patients with CHB, suggest that amphipathic polymers could become an important new tool in the treatment of CHB.
