艾格生物制药公司在FDA召开D肝病毒注册计划后宣布积极指导

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Eiger BioPharmaceuticals Announces Positive Guidance Following FDA Meeting on Hepatitis Delta Virus Registration Program

- Phase 3 D-LIVR Trial Planned to Initiate in Second Half 2018
Eiger BioPharmaceuticals (PRNewsFoto/Eiger BioPharmaceuticals, Inc.)

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Eiger BioPharmaceuticals, Inc.

Mar 21, 2018, 08:00 ET

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PALO ALTO, Calif., March 21, 2018 /PRNewswire/ -- Eiger BioPharmaceuticals, Inc. (Nasdaq: EIGR), focused on the development and commercialization of targeted therapies for rare diseases, announced today positive FDA guidance from a face to face discussion on the Hepatitis Delta Virus (HDV) program in February, including agreement that a single, registration trial in HDV can support an NDA filing.

D-LIVR (Delta Liver Improvement and Virologic Response in HDV) is expected to be an international, multi-center, Phase 3 study of approximately 300 patients to evaluate an all-oral arm of lonafarnib (LNF) + ritonavir (RTV) and a combination arm of LNF + RTV + pegylated interferon-alfa (PEG IFN-α), with each arm to be compared to a placebo arm (background HBV nucleos(t)ide only), in HDV-infected patients.  A PEG IFN-α alone arm will be dosed to demonstrate contribution of effect only.  The LNF containing arms will not be required to demonstrate superiority over PEG IFN-α alone.  The company is currently defining primary and secondary endpoints with the FDA.

"We are very pleased by the collaborative discussion with FDA and look forward to our planned advancement of the Phase 3 program for chronic HDV later this year," said David Apelian, MD, PhD, MBA, Chief Operating Officer and Executive Medical Officer.

The Agency discussion also supported the development of pegylated interferon lambda (Lambda) in HDV infection and based on that discussion Eiger plans a Phase 2 study of Lambda in combination with LNF and RTV.  LIFT (Lambda InterFeron combo-Therapy) is an open-label, Phase 2 study evaluating Lambda + LNF + RTV in approximately 26 HDV-infected patients.  Patients will be dosed for 24 weeks + undergo follow up for 24 weeks.  Primary endpoint will be ≥ 2 log decline in HDV RNA at end of treatment.  Secondary endpoints will include histology (>2 point improvement in histological activity index and no progression in fibrosis) at end of treatment.  LIFT will be conducted within the National Institutes of Health (NIH) at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and enrollment is planned for 2Q 2018.

"We look forward to advancing a single pivotal trial in HDV using a lonafarnib-based regimen," said David Cory, President and Chief Executive Officer.  "We are executing on our goal to develop the first approved therapy for HDV patients, with opportunities for label expansion and increased therapeutic options in the future.  We expect to share additional information on the planned registration program in 2Q 2018."

About Lonafarnib
Lonafarnib is a well-characterized, late-stage, orally active inhibitor of farnesyl transferase, an enzyme involved in modification of proteins through a process called prenylation.  HDV uses this host cell process inside liver cells to complete a key step in its life cycle.  Lonafarnib inhibits the prenylation step of HDV replication inside liver cells and blocks the virus life cycle at the stage of assembly.  Lonafarnib has been dosed in over 120 HDV-infected patients across international academic centers and is in Phase 2 development for HDV.  Lonafarnib has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), and Fast Track Designation by U.S. FDA.  Lonafarnib is not approved for any indication, and is licensed from Merck Sharp & Dohme Corp. (known as MSD outside of the United States and Canada).

About Pegylated Interferon Lambda (Lambda)
Lambda is a well-characterized, late-stage, first in class, type III interferon (IFN) that stimulates immune responses that are critical for the development of host protection during viral infections.  Lambda targets type III IFN receptors which are distinct from the type I IFN receptors targeted by IFN alfa.  These type III receptors are highly expressed on hepatocytes with limited expression on hematopoietic and central nervous system cells, which may reduce off-target effects and improve tolerability of Lambda.  Although Lambda does not use the IFN alfa receptor, signaling through either the IFN Lambda or IFN alfa receptor complexes results in the activation of the same Jak-STAT signal transduction cascade.

Eiger licensed worldwide rights to Lambda from Bristol-Myers Squibb in April 2016.  Lambda has been administered in HBV / HCV clinical trials involving over 3,000 subjects.  Lambda has not been approved for any indication.  Eiger has received Orphan Designation and Fast Track Designation for Lambda in HDV.

StephenW

艾格生物制药公司在FDA召开肝炎三角洲病毒注册计划后宣布积极指导
艾格生物制药公司在FDA召开肝炎三角洲病毒注册计划后宣布积极指导

- 计划于2018年下半年启动的3期D-LIVR试验
艾格生物制药公司（PRNewsFoto / Eiger BioPharmaceuticals，Inc.）

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艾格生物制药有限公司

2018年3月21日，东部时间08:00

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Eiger BioPharmaceuticals，Inc.（纳斯达克代码：EIGR）专注于罕见疾病靶向治疗的开发和商业化，今天宣布了面对面讨论的积极FDA指导意见在二月份的肝炎三角洲病毒（HDV）计划中，包括一项单一的HDV注册试验可以支持NDA申请的协议。

D-LIVR（三角洲肝脏改善和HDV病毒学应答）预计将是约300名患者的国际多中心3期临床试验，用于评估洛尼那韦（LNF）+利托那韦（RTV）在HDV感染的患者中，将LNF + RTV +聚乙二醇化干扰素-α（PEG IFN-α）的组合臂与每个手臂与安慰剂组（仅背景HBV核苷（t）ide）进行比较。仅PEG-IFN-α单独给药以证明仅有作用。含有LNF的臂不需要单独显示优于PEG IFN-α的优势。该公司目前正在与FDA确定主要和次要终点。

“我们对与FDA的合作性讨论感到非常高兴，并期待今年晚些时候我们计划推进慢性HDV第3期计划，”医学博士，工商管理硕士，首席运营官兼执行医学官David Apelian说。

该机构的讨论还支持聚乙二醇化干扰素λ（λ）在HDV感染中的发展，并基于该讨论，艾格计划将Lambda与LNF和RTV结合进行2期研究。 LIFT（Lambda InterFeron组合疗法）是一项开放标签的2期临床研究，评估约26名HDV感染患者的Lambda + LNF + RTV。患者将服药24周+接受随访24周。在治疗结束时，主要终点将HDV RNA降低≥2 log。次要终点包括组织学（治疗结束时组织学活性指数改善> 2分，纤维化无进展）。 LIFT将在美国国立卫生研究院（NIH）内的全国糖尿病和消化和肾脏疾病研究所（NIDDK）内进行，并计划在2018年第二季度注册。

“我们期待着使用基于洛那法尼的方案推进HDV单一关键试验，”总裁兼首席执行官David Cory说。 “我们正在执行我们的目标，即为HDV患者开发首个批准的治疗方案，未来有机会扩大标签并增加治疗选择。我们预计将在2018年第二季度分享有关计划注册计划的更多信息。”

关于Lonafarnib
Lonafarnib是一种很好的特征性的晚期口服活性法尼基转移酶抑制剂，它是一种通过称为戊二酰化的过程参与蛋白质修饰的酶。 HDV利用肝细胞内的这种宿主细胞过程完成其生命周期的关键步骤。 Lonafarnib抑制肝细胞内HDV复制的异戊烯化步骤，并在组装阶段阻断病毒生命周期。 Lonafarnib已经在国际学术中心为120多名HDV感染患者服药，目前正处于HDV的第二阶段开发阶段。 Lonafarnib已被美国食品和药物管理局（FDA）和欧洲药品管理局（EMA）授予孤儿药品名称，并获得美国FDA的快速通道指定。 Lonafarnib未被批准用于任何适应症，并且由Merck Sharp＆Dohme Corp.（在美国和加拿大以外称为MSD）许可。

关于聚乙二醇化干扰素Lambda（Lambda）
Lambda是一种特征良好的晚期第一类III型干扰素（IFN），可刺激对病毒感染期间宿主保护发展至关重要的免疫应答。 λ靶向III型IFN受体，其不同于IFNα靶向的I型IFN受体。这些III型受体在肝细胞上高表达，对造血和中枢神经系统细胞的表达有限，这可减少脱靶效应并提高Lambda的耐受性。尽管Lambda不使用IFNα受体，但通过IFNλ或IFNα受体复合物的信号传导导致相同Jak-STAT信号转导级联的活化。

艾格于2016年4月授权Bristol-Myers Squibb从Lambda获得世界范围的权利.Lambda已经应用于涉及3,000多个科目的HBV / HCV临床试验。 Lambda尚未被批准用于任何指示。艾格在HDV获得Lambda的孤儿指定和快速通道指定。