Eiger BioPharmaceuticals公布正面2期LIMT研究结束治疗数据与聚乙二

StephenW

Eiger BioPharmaceuticals Announces Positive Phase 2 LIMT Study End of Treatment Data with Pegylated Interferon Lambda Monotherapy in Hepatitis Delta Virus (HDV) Infection

- Lambda Antiviral Activity Demonstrated in HDV Infection

- Currently Dosing Lambda in Combination with Lonafarnib in HDV Infection
Eiger BioPharmaceuticals (PRNewsFoto/Eiger BioPharmaceuticals, Inc.)

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PALO ALTO, Calif., Oct. 17, 2018 /PRNewswire/ -- Eiger BioPharmaceuticals, Inc., (NASDAQ: EIGR) today announced positive data with Pegylated Interferon Lambda (Lambda) in the Phase 2 LIMT HDV (Lambda Interferon MonoTherapy in Hepatitis Delta Virus) Study.  LIMT HDV enrolled a total of 33 patients, randomized to Lambda 180 μg (N=16) or Lambda 120 μg (N=17), respectively, with weekly subcutaneous injections for 48 weeks in patients with chronic HDV.  Lambda is a first in class, type III interferon, in development for the treatment of HDV.

At Week 48, patients in the 180 μg Lambda treated group experienced a -2.4 log10 mean decline in HDV-RNA, with 6 of 10 (60%) experiencing ≥2 log10 decline, 4 of 10 (40%) patients were HDV-RNA negative at end of treatment.  At Week 48, patients in the 120 μg Lambda treated group experienced a -1.5 log10 mean decline in HDV RNA, with 6 of 14 (42.9%) experiencing ≥2 log10 decline, 2 of 14 (14.3%) patients were HDV-RNA negative at end of treatment.  The most common adverse events included mild to moderate flu-like symptoms and elevated transaminase levels.

"Lambda interferon demonstrated better tolerability in HDV-infected patients who were previously treated with Alfa interferon," said LIMT HDV Study Co-Lead Investigators, Ohad Etzion, MD, Director in the Department of Gastroenterology and Liver Diseases at Soroka University Medical Center and Saeed Hamid, MD, Chairman and Professor in Section of Gastroenterology, Department of Medicine, Aga Khan University.  "Fewer episodes of cytopenia, flu-like symptoms, and psychiatric events in this study make Lambda interferon particularly attractive for further development as a monotherapy or in combination with other treatments for HDV."

"Lambda is the second proprietary product in the Eiger pipeline for development as a monotherapy or combination therapy in HDV," said David Apelian, COO and Executive Medical Officer at Eiger.  "Lambda is now dosing in combination with Lonafarnib boosted with Ritonavir in HDV-infected patients in the Phase 2 LIFT study at the National Institutes of Health (NIH).  We look forward to end of treatment data from this proprietary Lambda-Lonafarnib combination in 2019."  

The company plans to share additional details from the Lambda LIMT study at the following AASLD 2018 events in San Francisco in November:

    Liver Institute and Foundation for Education and Research (L.I.F.E.R.) Meeting: The Search for HBV/HDV Cure: Challenges for Industry; "Eiger Phase 3 HDV Lonafarnib 'D-LIVR' Study and Phase 2 HDV Lambda 'LIFT' Study," November 9
    Eiger Phase 3 D-LIVR Study Investigator Reception, November 9
    Hepatitis Delta International Network (HDIN) Meeting; "HDV Program Update: Lonafarnib Boosted with Ritonavir and Pegylated Interferon Lambda"; November 10

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 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.

About LIMT (Lambda Monotherapy) Study
LIMT HDV is a 1:1 randomized, open-label study of Lambda 120 or 180 μg subcutaneous injections administered weekly for 48 weeks in 33 patients with chronic HDV.  End of treatment will be followed by a treatment-free 24-week observation period.  The primary objective of the Phase 2 study is to evaluate the safety, tolerability, and efficacy of treatment with two dose levels of Lambda monotherapy in patients with chronic HDV infection.  All patients are administered an anti-hepatitis B virus nucleos(t)ide analog throughout the study.  LIMT HDV is an international study with sites in New Zealand, Israel and Pakistan.

About LIFT (Lambda Combo Therapy) Study
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 is being conducted within the National Institutes of Health (NIH) at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

StephenW

Eiger BioPharmaceuticals公布正面2期LIMT研究结束治疗数据与聚乙二醇干扰素Lambda单药治疗肝炎三角洲病毒（HDV）感染

- 在HDV感染中表现出的Lambda抗病毒活性

- 目前在HDV感染中与Lonafarnib联合给药Lambda
Eiger BioPharmaceuticals（PRNewsFoto / Eiger BioPharmaceuticals，Inc。）

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加利福尼亚州帕洛阿尔托，2018年10月17日/美通社-PR Newswire / - Eiger BioPharmaceuticals，Inc。（纳斯达克股票代码：EIGR）今天宣布在第2阶段LIMT HDV中使用Pegylated干扰素Lambda（Lambda）的正面数据（Lambda Interferon MonoTherapy in Hepatitis） Delta病毒研究。 LIMT HDV共招募了33名患者，分别随机分为180μg（N = 16）或Lambda120μg（N = 17），每周皮下注射48周治疗慢性HDV患者。 Lambda是一种先进的III型干扰素，用于治疗HDV。

在第48周，180μgRambda治疗组的患者HDV-RNA平均下降-2.4 log10，其中6名（60％）经历≥2log10下降，10名中有4名（40％）患者为HDV-RNA治疗结束时阴性。在第48周，120μgRambda治疗组的患者HDV RNA平均下降-1.5 log10，其中14例（42.9％）经历≥2log10下降，14例（14.3％）患者中有2例为HDV-RNA阴性在治疗结束时。最常见的不良事件包括轻度至中度流感样症状和转氨酶水平升高。

“Lambda干扰素在以前接受过阿尔法干扰素治疗的HDV感染患者中表现出更好的耐受性，”LIMT HDV研究共同首席研究人员，Ohad Etzion医学博士，Soroka大学医学中心和Saeed消化内科和肝病科主任哈米德，医学博士，阿加汗大学医学系消化内科主任和教授。 “本研究中较少发生的血细胞减少，流感样症状和精神事件使得Lambda干扰素特别适合作为单一疗法或与其他HDV治疗相结合的进一步发展。”

“Lambda是Eiger管道中用于HDV单药治疗或联合治疗的第二个专利产品，”Eiger首席运营官兼执行医疗官David Apelian说。 “在美国国立卫生研究院（NIH）的2期LIFT研究中，Lambda现在与Lonafarnib联合使用Ritonavir在HDV感染患者中加强治疗。我们期待2019年该专有Lambda-Lonafarnib组合的治疗数据结束“。

该公司计划在11月的旧金山举行的以下AASLD 2018年活动中分享Lambda LIMT研究的其他细节：

    肝脏研究所和教育与研究基金会（L.I.F.E.R。）会议：寻找HBV / HDV治疗：对工业的挑战; “Eiger Phase 3 HDV Lonafarnib'D-LIVR'研究和第2阶段HDV Lambda'LIFT'研究，”11月9日
    艾格尔3期D-LIVR研究调查员招待会，11月9日
    三角洲国际网络（HDIN）会议; “HDV计划更新：Lonafarnib与Ritonavir和Pegylated Interferon Lambda一起推动”; 11月10日

关于Pegylated Interferon Lambda（Lambda）
Lambda是一种充分表征的晚期，一流的III型干扰素（IFN），可刺激免疫反应，这对病毒感染期间宿主保护的发展至关重要。 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度表达，在造血和中枢神经系统细胞上表达有限，这降低了脱靶效应并改善了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的Jak-STAT信号转导级联的激活。

2016年4月，Eiger从Bristol-Myers Squibb获得Lambda的全球版权.Lambda已经在涉及3,000多名受试者的HBV / HCV临床试验中进行了管理。 Lambda尚未获得任何适应症的批准。 Eiger已获得HDV Lambda的孤儿指定和快速指定。

关于LIMT（Lambda Monotherapy）研究
LIMT HDV是一项1：1的随机，开放标签研究，对33名慢性HDV患者进行Lambda 120或180μg皮下注射，每周一次，共48周。治疗结束后将进行无治疗的24周观察期。第2阶段研究的主要目的是评估两种剂量水平的Lambda单药治疗慢性HDV感染患者的安全性，耐受性和疗效。在整个研究中，所有患者都给予抗乙型肝炎病毒核苷（酸）类似物。 LIMT HDV是一项国际研究，在新西兰，以色列和巴基斯坦设有分支机构。
关于LIFT（Lambda Combo Therapy）研究
LIFT（Lambda InterFeron组合疗法）是一项开放标签的2期研究，评估约26名HDV感染患者的Lambda + LNF + RTV。 患者将服用24周+接受随访24周。 治疗结束时，HDV RNA的主要终点≥2log对数下降。 次要终点将包括治疗结束时的组织学（组织学活性指数> 2点改善，纤维化无进展）。 LIFT正在美国国立卫生研究院（NIH）的国家糖尿病和消化和肾脏疾病研究所（NIDDK）进行。