REP2139证明HBV和HDV均可功能治愈

StephenW

REP2139 demonstrates functional cure in both HBV, HDV
December 26, 2019

Results from the REP 301 and REP 401 studies showed combination therapy with REP2139 and pegylated interferon led to high rates of hepatitis B seroconversion in patients coinfected with hepatitis B and hepatitis D with more than half of treated patients also achieving functional cure of hepatitis D, according to data presented at HEP DART 2019.

“The REP 301 and REP 401 studies are the only studies to date using an investigational agent — nucleic acid polymers or NAPs — which has demonstrated long-term functional cure of HBV, HBV/HDV coinfection, and normalization of liver function with reversal of inflammation and fibrosis,” Andrew Vaillant, PhD, chief scientific officer at Replicor, told Healio Gastroenterology and Liver Disease.

Vaillant and colleagues designed the REP 401 study to examine the safety and efficacy of combination therapy with tenofovir disoproxil fumarate (TDF), pegylated interferon alfa-2a (pegIFN) and two NAPs (REP 2139 and REP 2165) in 40 patients with chronic HBV who tested HBV e-antigen negative . Patients received treatment for 48 weeks.

Therapeutic outcomes from REP 401 showed seroconversion in 53% of patients, with 39% achieving virologic control and 39% achieving functional cure. Additionally, the investigators estimated that 78% achieved a clinical benefit including lowered risk for progression and risk for hepatocellular carcinoma.

Investigators of the REP 301-LTF study followed 12 HBeAg-negative patients coinfected with HBV/HDV who previously received treatment with REP 2139 for 15 weeks, REP 2139 with pegIFN for 15 weeks, then pegIFN for 33 weeks. Follow-up was approximately 3.5 years.

In this study, 64% of patients achieved functional cure of HDV and 82% achieved a 2 log 10 or more reduction in HDV RNA from baseline. More than half of the patients also achieved normal alanine aminotransferase (73%) and normal or declining liver stiffness (64%).

“Replicor believes that REP 2139-[magnesium] based combination therapy will become the new standard of care for the treatment of HBV and HBV/HDV infection,” Vaillant said. – by Talitha Bennett

Reference: Bazinet M, et al. Transaminase flares during HBsAg reduction to < 1 IU/mL are correlated with the establishment of functional cure of HBV following NAP-based combination therapy. Presented at: HEP DART 2019; Dec. 12-19, 2019; Kauai, Hawaii.

Disclosures: Vaillant reports being an employee and shareholder in Replicor.

StephenW

REP2139证明HBV和HDV均可功能治愈
2019年12月26日

REP 301和REP 401研究的结果表明，与REP2139和聚乙二醇化干扰素联合治疗可导致乙型肝炎和D型肝炎合并感染的患者发生乙型肝炎的血清转化率高，接受治疗的患者中有一半以上也能实现D型肝炎的功能性治愈。到在HEP DART 2019上展示的数据。

“ REP 301和REP 401研究是迄今为止仅有的使用研究剂（核酸聚合物或NAP）的研究，该研究剂已证明HBV，HBV / HDV合并感染的长期功能性治愈以及肝功能正常化以及炎症逆转与纤维化有关，” Replicor首席科学官Andrew Vaillant博士对Healio胃肠病学和肝病杂志表示。

Vaillant和同事设计了REP 401研究，以检查40例慢性HBV病人中联合替诺福韦富马酸替诺福韦酯（TDF），聚乙二醇干扰素α-2a（pegIFN）和两种NAP（REP 2139和REP 2165）联合治疗的安全性和有效性。测试的HBV电子抗原阴性。患者接受了48周的治疗。

REP 401的治疗结果显示53％的患者发生血清转化，其中39％实现了病毒学控制，39％实现了功能性治愈。此外，研究人员估计78％的患者获得了临床益处，包括降低了进展风险和肝细胞癌风险。

REP 301-LTF研究的研究者追踪了12例合并感染HBV / HDV的HBeAg阴性患者，他们先前曾接受REP 2139治疗15周，REP 2139接受pegIFN治疗15周，然后接受pegIFN治疗33周。随访时间约为3.5年。

在这项研究中，有64％的患者实现了HDV的功能性治愈，而82％的患者实现了HDV RNA从基线水平下降2 log 10或更多。超过一半的患者也达到了正常的丙氨酸转氨酶（73％）和正常或下降的肝硬度（64％）。

“复制者认为，基于REP 2139- [镁]的联合疗法将成为治疗HBV和HBV / HDV感染的新护理标准，” Vaillant说。 –塔利莎·贝内特（Talitha Bennett）

参考：Bazinet M等。在基于NAP的联合治疗后，HBsAg降低至<1 IU / mL期间的转氨酶耀斑与HBV功能性治愈的建立相关。呈现在：HEP DART 2019; 2019年12月12-19日;夏威夷考艾岛。

披露：Vaillant报告是Replicor的雇员和股东。

灵魂不屈

感谢分享，这药应该快揭开神秘面纱了吧。

齐欢畅

平凡之路123

这么好的药，既也没人合作，也没人收购。
原来资本市场里没有聪明人，都是瞎子啊。

zyren

两种NAP（REP 2139和REP 2165）的联合都有效吗？ REP 2165网上查好像是替诺？
也没有设置任何前置条件，大三小三不用区分吗？

StephenW

回复 zyren 的帖子

REP 2165与替诺无关.   REP 2165 是 REP2139 另一种形式, 改善组织(tissue)清除率.

计划是用 rep2139的皮下(SC)注射形式在将来的临床试验.