J Viral Hepat. 2018 Nov 19. doi: 10.1111/jvh.13044. [Epub ahead of print]
Variants of hepatitis B virus surface antigen observed during therapy with nucleic acid polymer REP 2139-Ca have no influence on treatment outcome and its detection by diagnostic assays.
Mijočević H1, Karimzadeh H1,2, Seebach J1, Usman Z3, Mamun AM4, Bazinet M5, Vaillant A5, Roggendorf M1.
Author information
1
Institute of Virology, Technische Universität München, Munich, Germany.
2
Department of Medicine II, University Hospital Munich-Grosshadern, Munich, Germany.
3
Department of Bioinformatics, Wissenschaftszentrum Weihenstephan, Technische Universität München, Munich, Germany.
4
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
5
Replicor Inc, Montreal, Canada.
Abstract
The treatment of patients suffering from HBeAg positive chronic hepatitis B with REP 2139-Ca resulted in potent reductions in HBsAg and HBV DNA, seroconversion to anti-HBs and the establishment of functional control of infection. In this cohort of 12 patients, we investigated whether differences between HBsAg sequences might explain lack of response to REP 2139-Ca observed in 3 of 12 patients. We also assessed if the reduction or complete loss of HBsAg in serum observed during therapy were caused by mutations in the "a" determinant preventing the detection of HBsAg by standard diagnostic assays. The complete pre-S/S open reading frame (ORF) was sequenced and pre-S1, pre-S2 and S amino acid sequences were analysed. We found no major differences between pre-S1, pre-S2 and S sequences in responders and non-responders correlated with low reduction of HBsAg. In addition, we found no mutations in the "a" determinant that would significantly affect the reactivity of HBsAg in diagnostic assays. These results demonstrate that the amino acid sequence of complete pre-S/S ORF has no direct influence on response to REP 2139-Ca therapy. This article is protected by copyright. All rights reserved.
KEYWORDS:
HBsAg; Mutation; hepatitis B virus; nucleic acid polymer; therapy
Replicor announces publication of new study validating HBsAg responses driven by REP 2139
MONTREAL, November 21st, 2018 – Replicor Inc., a privately held biopharmaceutical company targeting a cure for patients with chronic hepatitis B virus (HBV) and chronic HBV and hepatitis delta virus (HDV) co-infection, announces the publication of new data validating the clearance of HBsAg in response to NAP therapy in the Journal of Viral Hepatitis (https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvh.13044).
The article is entitled “Variants of hepatitis B virus surface antigen observed during therapy with nucleic acid polymer REP 2139‐Ca have no influence on treatment outcome and its detection by diagnostic assays.” This study adds to data previously published from Replicor’s ongoing collaboration with Dr. Michael Roggendorf at the Technical University of Munich (TUM), Germany, confirming that the HBsAg reductions and loss of HBsAg which uniquely occur in a high proportion of patients receiving REP 2139 are real.
Dr. Andrew Vaillant, CSO at Replicor commented, “From the initiation of our first clinical study, NAP-based combination therapy was the first, and, is still the only therapeutic approach that consistently demonstrates high rates of rapid serum HBsAg reduction and loss and restoration of control of HBV and HDV infection in the absence of therapy. Understandably, these results led to some skepticism concerning the validity of the HBsAg losses occurring with REP 2139. Early on in the clinical development of NAPs, we turned to Dr. Roggendorf and the virology group at TUM to demonstrate that these HBsAg losses are real and this publication is the second from this ongoing collaboration to show that REP 2139-mediated HBsAg loss is real.”
Previously published data in The Lancet Gastroenterology & Hepatology (https://www.thelancet.com/journals/langas/article/PIIS2468-1253(17)30288-1/fulltext) demonstrated that REP 2139 does not interfere with a broad suite of protein and nucleic acid-based assays for HBV and HDV. In the current study, HBsAg strains which cannot be detected by the industry standard HBsAg test platforms used in Replicor’s clinical studies were not observed at any time during REP 2139 exposure. These data confirm the validity of HBsAg responses observed in all clinical studies with REP 2139-Ca or REP 2139-Mg.
Dr. Vaillant added, “This study also showed that HBsAg sequences present in different participants at baseline had no influence on their HBsAg response to REP 2139, consistent with our data showing that NAPs effect the assembly and secretion of subviral particles by interfering with a host protein involved in their formation.”
About Replicor
Replicor is a privately held biopharmaceutical company with the most advanced animal and human 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 co-infection. For further information about Replicor please visit our website at www.replicor.com.作者: StephenW 时间: 2018-11-22 14:36
Replicor的CSO Andrew Vaillant博士评论说:“从我们的第一次临床研究开始,基于NAP的联合治疗是第一次,并且仍然是唯一一种能够持续证明血清HBsAg快速降低和丢失率的治疗方法。在没有治疗的情况下恢复对HBV和HDV感染的控制。可以理解的是,这些结果导致对REP 2139中HBsAg损失的有效性产生了一些怀疑。在NAP的临床开发早期,我们转向Roggendorf博士和TUM的病毒学组,以证明这些HBsAg损失是真实的,该出版物是此次合作中的第二份,表明REP 2139介导的HBsAg损失是真实的。“