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REP 9AC / REP 9AC’: Potent HBsAg release inhibitors that can rapidly elicit durable immunological control of infection in patients with chronic hepatitis B
Mamun-Al-Mahtab1, Michel Bazinet2 and Andrew Vaillant2
1Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
2REPLICor Inc., Montreal, Canada
BACKGROUND: HBsAg suppresses host immunity and permits chronicity of HBV infection. REP9AC / REP9AC’ are nucleic acid-based polymers (NAPs) that block HBsAg release from infected hepatocytes. The current clinical results with REP9AC and a 4th generation NAP (REP9AC’) are disclosed.
METHODS: Patients with pre-treatment HBV DNA titers between 106 and 1012 copies/ml were treated by IV infusion. Virologic response was assessed using the Cobas and Architect testing platforms.
RESULTS (REP9AC): > 99.5% reduction of HBsAg occurred in seven of eight patients within 7 days to 32 weeks of treatment. All responders achieved 3 - 7 log reductions in HBV DNA. Four responders achieved complete control of their infection with 20-44 weeks of treatment (HBV DNA < 500cpm). Off treatment, three patients had sustained immunological control of their infection (HBV DNA < 500cpm, and HBsAg < 10 IU) for 12-24 months. All other patients had partial immunological control of their infection (> 90% reductions in HBsAg and 2-7 log reductions in HBV DNA). Mild pro-inflammatory side-effects accompanied drug administration.
RESULTS (REP9AC’): REP9AC’ is more stable with reduced pro-inflammatory activity compared to REP9AC. Interim data show robust HBsAg reductions in all seven patients in the first 10 weeks of treatment. Three patients have already experienced a 3-4 log decline in HBV DNA. Pro-inflammatory side-effects during administration were substantially reduced.
CONCLUSIONS: NAPs can affect rapid clearance of HBsAg, allowing restoration of host immunity. These results suggest that NAPs may become an important new tool in the treatment of chronic hepatitis B.
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