Updates in the REP 301 (HBV/HDV coinfection) and REP 401 (HBV infection) studies demonstrated important advances:
1. In the REP 301 study, previously reported functional control at 24 weeks follow-up of HBV (5/12 patients) and HDV (7/12 patients) was shown to be maintained at one year, demonstrating the durability of functional control established with NAP based therapy (poster LBP-507).
2. In the REP 401 study, 30 patients have received at least 12 weeks of NAP exposure and serum HBsAg response over time continues to improve: current reductions from baseline presented were >1log in 29 patients, >2logs in 25 patients, >4logs in 19 patients, with HBsAg loss in 14 patients. Improved efficacy of pegIFN (marked anti-HBs production and/or therapeutic transaminase flares) occurred in all patients with HBsAg reduction > 4 log (poster THU-154).
3. Surprisingly, analysis of serum HBsAg, HBeAg, HBcrAg, HBV RNA, HBV DNA and HDV RNA in both studies indicated that circulating HBsAg appears to be almost completely derived from integration.
“The notion that almost all circulating HBsAg is derived from integration has important therapeutic implications,” said CSO Dr. Andrew Vaillant. “As the primary immunosuppressive agent in HBV and HDV infections, HBsAg removal will be critical. It’s very likely that new investigational agents with other antiviral mechanisms will still require agents directly targeting HBsAg release like NAPs in order to achieve a high rate of functional control.” Dr. Bazinet, CEO, added “our continually expanding clinical data continues to demonstrate that significant rates of functional control of HBV and HDV can be achieved with currently approved drugs and NAPs.”
Deep sequencing of HBsAg in the previous REP 102 study showed no selection pressure with REP 2139, further validating the serum HBsAg response to NAP therapy (Poster THU-155). A recently developed tissue culture system now reproduces for the first time the post-entry effects of NAPs on secretion of HBV particles observed preclinically and clinically (Poster THU-156).
Dr. Vaillant remarked, “The ability to model the post-entry effects of NAPs in tissue culture is the culmination of more than 6 years of work which including various collaborators worldwide. With this tool finally in place, the host mechanisms targeted by NAPs can now begin to be explored.”
Replicor is a privately held biopharmaceutical company with the most advanced clinical data in the development of the cure for HBV and HDV. The company is dedicated to accelerating the development of an effective treatment for patients with HBV and HBV/HDV infection. www.replicor.com