Enanta Pharmaceuticals宣布其乙型肝炎病毒的主要核心抑制剂EDP-514

StephenW

Enanta Pharmaceuticals Announces Clinical Trial Progress for EDP-514, its Lead Core Inhibitor for Hepatitis B Virus

    Initiated Phase 1b Study Evaluating EDP-514 in Viremic HBV Patients; Preliminary Data Anticipated in 1H 2021
    Resumed Phase 1b Study Assessing Safety and Antiviral Activity of EDP-514 in NUC-Suppressed HBV Patients; Topline Results Anticipated in 2Q 2021

July 09, 2020 07:01 AM Eastern Daylight Time

WATERTOWN, Mass.--(BUSINESS WIRE)--Enanta Pharmaceuticals, Inc., (NASDAQ: ENTA), a clinical-stage biotechnology company dedicated to creating small molecule drugs for viral infections and liver diseases, today announced advancements in its hepatitis B virus (HBV) program evaluating EDP-514 across different patient populations. Enanta initiated, as planned, a Phase 1b clinical trial in viremic HBV patients, and resumed its ongoing Phase 1b study in HBV patients treated with a nucleos(t)ide reverse transcriptase inhibitor (NUC-suppressed patients), which was previously paused due to the COVID-19 pandemic. EDP-514 is a novel class II HBV core inhibitor that has Fast Track Designation from the FDA.

“HBV is a potentially life-threatening liver infection, affecting over 250 million people worldwide for which there is no functional cure. We are pleased to continue to advance our HBV program with two clinical studies evaluating EDP-514 in chronic HBV patients – one in viremic patients not currently on therapy and the second in patients with HBV infection that is NUC-suppressed,” said Jay R. Luly, President and Chief Executive Officer of Enanta Pharmaceuticals. “EDP-514, a novel core inhibitor of HBV replication, leverages our strength in compound optimization and targeted rational design, enabling potent anti-HBV activity at multiple steps in the HBV lifecycle. We are excited to further investigate EDP-514 in viremic HBV patients, and look forward to reporting preliminary safety and virologic data in the first half of 2021, while also completing our study in NUC-suppressed patients with topline data expected in the second quarter of 2021. As we look toward these catalysts, we are continuing to monitor any impact of the COVID-19 pandemic on our clinical progress.”

The randomized, double-blind, placebo-controlled Phase 1b study in viremic chronic HBV subjects not currently on therapy is designed to evaluate the safety, tolerability, pharmacokinetics and antiviral activity of orally administered EDP-514 over a 28-day period. The study is planned to enroll 24 subjects who will be randomized to receive one of three multiple ascending doses of EDP-514 or placebo.

The randomized, double-blind, placebo-controlled Phase 1b study in NUC-suppressed subjects with chronic HBV infection is Part 2 of a Phase 1a/1b study. Part 2 of the study is designed to evaluate the safety, tolerability, pharmacokinetics and antiviral activity of orally administered EDP-514 over a 28-day period. The study is planned to enroll 24 subjects who will be randomized to receive one of three multiple ascending doses of EDP-514 or placebo.

In Part 1 of the Phase 1a/1b study, EDP-514 was studied in healthy subjects who received single or multiple doses for up to 14 days. EDP-514 was well tolerated with a favorable safety profile. Treatment-emergent adverse events were infrequent and mild in intensity. No patients discontinued EDP-514 due to an adverse event. Additionally, the pharmacokinetic profile was supportive of once-daily dosing. Enanta plans on presenting additional data from Part 1 of the Phase 1a/1b study in healthy volunteers in a poster presentation at the European Association for the Study of the Liver’s (EASL) Digital International Liver Congress, August 27-29, 2020.

About EDP-514
EDP-514, a novel class II hepatitis B virus (HBV) core inhibitor, is Enanta’s lead core inhibitor candidate. Core inhibitors, also known as capsid assembly modulators or core protein allosteric modulators, are a novel class of HBV replication inhibitors that have been shown to act at multiple steps in the HBV lifecycle. Preclinical data demonstrate that EDP-514 is a potent inhibitor of HBV replication and prevents the denovo formation of new cccDNA in primary human hepatocytes when given early during HBV infection. In vitro data also show that EDP-514 is pan-genotypic, and that combinations of EDP-514 with a nucleos(t)ide reverse-transcriptase inhibitor (NRTI), the current anti-viral therapy for HBV, or with a class I core inhibitor, result in additive to synergistic antiviral effects. ln vivo models of EDP-514 demonstrate excellent efficacy with >4-log viral load reduction in HBV-infected PXB mice.

About Hepatitis B Virus
Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease. The virus is most commonly transmitted from mother to child during birth and delivery, as well as through contact with blood or other body fluids. It is estimated that over 250 million people have chronic HBV infection. According to the World Health Organization, there are approximately 887,000 deaths from HBV infection per year mostly from cirrhosis and hepatocellular carcinoma or primary liver cancer. As of 2016, of the people living with HBV infection, only 27 million were aware of their infection, and only 4.5 million of those received treatment.1

Current approaches to treatment include interferon therapy and/or inhibitors of HBV reverse transcriptase. Treatment with interferon offers poor cure rates and is accompanied by serious side effects. Reverse transcriptase inhibitors can be very effective at suppressing the virus but rarely result in full eradication of the virus from the liver.

About Enanta
Enanta is using its robust, chemistry-driven approach and drug discovery capabilities to become a leader in the discovery and development of small molecule drugs for the treatment of viral infections and liver diseases. Enanta’s research and development efforts have produced clinical candidates for the following disease targets: respiratory syncytial virus (RSV), non-alcoholic steatohepatitis (NASH), hepatitis B virus (HBV), human metapneumovirus (hMPV) and SARS-CoV-2 (COVID-19).

Enanta’s research and development activities are funded by royalties from hepatitis C virus (HCV) products developed under its collaboration with AbbVie. Glecaprevir, a protease inhibitor discovered by Enanta, is sold by AbbVie in numerous countries as part of its leading treatment for chronic HCV infection under the tradenames MAVYRET® (U.S.) and MAVIRET® (ex-U.S.) (glecaprevir/pibrentasvir). Please visit www.enanta.com for more information.

StephenW

Enanta Pharmaceuticals宣布其乙型肝炎病毒的主要核心抑制剂EDP-514的临床试验进展

    开始1b期研究，评估病毒性HBV患者的EDP-514； 2021年1H预期的初步数据
    评估EDP-514在NUC抑制的HBV患者中的安全性和抗病毒活性的1b阶段恢复研究；预计2021年第二季度的主要业绩

2020年7月9日，东部夏令时间上午07:01

马萨诸塞州沃特敦-（美国商业资讯）-临床阶段生物技术公司Enanta Pharmaceuticals，Inc.（纳斯达克股票代码：ENTA）致力于生产用于病毒感染和肝病的小分子药物，该公司今天宣布其乙型肝炎取得了进展病毒（HBV）计划，可评估不同患者人群的EDP-514。 Enanta按计划启动了针对病毒血症性HBV患者的1b期临床试验，并继续进行了接受核苷酸（t）逆转录酶抑制剂治疗的HBV患者（NUC抑制患者）的1b期临床研究，该试验先前因COVID-19大流行。 EDP​​-514是一种新颖的II类HBV核心抑制剂，具有FDA的快速通道认证。

HBV是一种潜在的威胁生命的肝脏感染，影响了全球超过2.5亿无法治愈的人。 Jay R说：“我们很高兴通过两项针对慢性HBV患者的EDP-514评价EDP-514的临床研究来继续推进HBV计划–一项是目前未接受治疗的病毒血症患者，另一项是被NUC抑制的HBV感染患者。” Enanta Pharmaceuticals总裁兼首席执行官Luly。 “ EDP-514是一种新型的HBV复制核心抑制剂，它利用我们在化合物优化和针对性合理设计方面的优势，在HBV生命周期的多个步骤中实现了强大的抗HBV活性。我们很高兴能进一步研究EDP-514在病毒性HBV患者中的应用，并期待在2021年上半年报告初步的安全性和病毒学数据，同时也完成了对NUC抑制患者的研究，并有望在第二季度获得顶线数据2021年，当我们期待这些催化剂时，我们将继续监测COVID-19大流行对我们临床进展的任何影响。”

针对目前尚未接受治疗的病毒性慢性HBV受试者进行的随机，双盲，安慰剂对照1b期研究旨在评估28天口服EDP-514的安全性，耐受性，药代动力学和抗病毒活性。该研究计划招募24名受试者，这些受试者将被随机分配接受EDP-514或安慰剂的三种多次递增剂量之一。

在NUC抑制的慢性HBV感染受试者中进行的随机，双盲，安慰剂对照1b期研究是1a / 1b期研究的第二部分。该研究的第2部分旨在评估28天口服EDP-514的安全性，耐受性，药代动力学和抗病毒活性。该研究计划招募24名受试者，这些受试者将被随机分配接受EDP-514或安慰剂的三种多次递增剂量之一。

在1a / 1b期研究的第1部分中，EDP-514在接受单次或多次剂量长达14天的健康受试者中进行了研究。 EDP​​-514具有良好的耐受性，并具有良好的安全性。突发性治疗不良事件很少见，强度轻。没有患者因不良事件而停用EDP-514。另外，药代动力学特征支持每天一次给药。 Enanta计划在2020年8月27日至29日举行的欧洲肝病研究协会（EASL）数字国际肝病大会上的海报展示中，向健康志愿者提供1a / 1b期研究的第1部分的其他数据。

关于EDP-514
EDP​​-514是一种新型的II类乙型肝炎病毒（HBV）核心抑制剂，是Enanta的主要核心抑制剂候选产品。核心抑制剂，也称为衣壳装配调节剂或核心蛋白变构调节剂，是一类新型的HBV复制抑制剂，已显示在HBV生命周期的多个步骤中起作用。临床前数据表明，在HBV感染早期给予EDP-514是有效的HBV复制抑制剂，并防止在原代人肝细胞中新的cccDNA的树突状形成。体外数据还显示EDP-514具有泛基因型，并且EDP-514与核苷酸（t）逆转录酶抑制剂（NRTI），当前的HBV抗病毒疗法或I类药物联合使用核心抑制剂，可产生协同抗病毒作用。 EDP​​-514的体内模型在HBV感染的PXB小鼠中表现出了卓越的功效，病毒载量减少了> 4-log。
关于乙型肝炎病毒
乙型肝炎是一种病毒感染，会侵袭肝脏并导致急性和慢性疾病。该病毒最常见的是在出生和分娩期间以及与血液或其他体液接触时从母亲传播给孩子。据估计，超过2.5亿人患有慢性HBV感染。根据世界卫生组织的数据，每年约有887，000例HBV感染死亡，主要死于肝硬化和肝细胞癌或原发性肝癌。截至2016年，在HBV感染者中，只有2700万人知道自己的感染，只有450万人接受了治疗1。

当前的治疗方法包括干扰素治疗和/或HBV逆转录酶抑制剂。干扰素治疗的治愈率低，并伴有严重的副作用。逆转录酶抑制剂在抑制病毒方面非常有效，但很少导致从肝脏完全消灭病毒。

关于Enanta
Enanta正在使用其强大的，化学驱动的方法和药物发现能力来成为发现和开发用于治疗病毒感染和肝病的小分子药物的领导者。 Enanta的研究和开发成果为以下疾病目标提供了临床候选药物：呼吸道合胞病毒（RSV），非酒精性脂肪性肝炎（NASH），乙型肝炎病毒（HBV），人间质肺炎病毒（hMPV）和SARS-CoV-2（COVID -19）。

Enanta的研发活动由与AbbVie合作开发的丙型肝炎病毒（HCV）产品的特许权使用费资助。由Enanta发现的蛋白酶抑制剂Glecaprevir被AbbVie在许多国家出售，作为其领先的慢性HCV感染治疗方法的一部分，商品名为MAVYRET®（美国）和MAVIRET®（ex-U.S。）（glecaprevir / pibrentasvir）。有关更多信息，请访问www.enanta.com。