Eiger在2020數字國際肝臟大會（TM）的晚期斷路器會議上宣布Peg

StephenW

PALO ALTO, Calif., Aug. 31, 2020 /PRNewswire/ -- Eiger BioPharmaceuticals, Inc. (Nasdaq:EIGR), focused on the development and commercialization of targeted, first-in-class therapies for serious rare and ultra-rare diseases, today announced results from a late-breaker poster presentation at The Digital International Liver Congress™ 2020 of end of treatment results of the Phase 2 LIFT Lambda – Lonafarnib combination study in patients infected with hepatitis delta virus (HDV).  The LIFT (Lambda InterFeron combo-Therapy) study is being conducted within the National Institutes of Health (NIH) at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).  Lambda is a first-in-class type III interferon in clinical development for HDV, the most severe form of human viral hepatitis. "We have previously presented promising results from multiple studies at NIDDK that Lonafarnib reduces HDV RNA viral load in patients infected with HDV," said Christopher Koh, MD, Principal Investigator at the NIDDK.  "Lambda and Lonafarnib combination Week 24 end of treatment results from the ongoing LIFT study represent a potential foundational combination treatment for HDV.  We will present Week 48 end of follow-up results from the LIFT study in the future."
LIFT is a Phase 2a open-label study of 26 adult patients with chronic HDV treated with Lambda 180 mcg once weekly in combination with Lonafarnib 50 mg boosted with ritonavir 100 mg twice daily for 24 weeks.  Primary efficacy endpoint is > 2 log decline in HDV RNA at end of treatment.  Median baseline evaluations included: ALT (64 IU/mL), AST (47 IU/mL), Ishak Fibrosis (3), modified HAI inflammation (9), HBV DNA (< 20 IU/mL) and log HDV RNA (4.74 IU/mL).
At Week 24 end of treatment, 25 of 26 patients (96%) achieved the Primary Endpoint of > 2 log decline in HDV RNA, 58% of patients were either Below Limit of Quantitation or Undetectable, and median HDV RNA decline was 3.2 log IU/mL (CI: 2.50-3.93, p<0.0001).  Combination therapy with Lambda and Lonafarnib in chronic HDV patients appears to be well tolerated for up to 6 months in most patients.  LIFT end of treatment results support continued exploration of this therapeutic combination in HDV.
Adverse events were mostly mild to moderate and included GI-related side effects, weight loss, hyperbilirubinemia, and anemia.  Per-protocol dose reductions occurred in 3 patients and discontinued in 4 patients, and were mostly due to known side effects related to peginterferon lambda.
About Peginterferon 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, resulting in activation of the same Jak-STAT signal transduction cascade.  Lambda 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.
Eiger licensed worldwide rights to Lambda from Bristol-Myers Squibb.  Eiger is developing Lambda as a monotherapy and in combination with Lonafarnib boosted with ritonavir.  Lambda is an investigational agent and not yet approved for any indication.  Eiger has received Orphan Designation by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), and Fast Track and Breakthrough Therapy Designation by FDA for Lambda in HDV.
About Lonafarnib
Lonafarnib is a well-characterized, late-stage, orally active, first-in-class inhibitor of farnesyl transferase, an enzyme involved in modification of proteins through a process called prenylation, a vital process in the life cycle of HDV.  Blocking prenylation of the large delta hepatitis antigen (LDHAg) reduces HDV replication.   
Lonafarnib has been dosed in over 120 HDV-infected patients across international academic centers and is in Phase 3 with a single, international, pivotal trial (D-LIVR Study).  Lonafarnib has been granted Orphan Drug designation by the U.S. FDA and European Medicines Agency (EMA), Fast Track and Breakthrough Therapy Designation by the U.S. FDA and PRIME designation by the EMA.  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 LIFT Study
LIFT (Lambda InterFeron combo-Therapy) is an open-label, Phase 2 study evaluating Lambda + Lonafarnib + Ritonavir in 26 HDV-infected patients.  Patients with quantifiable HDV RNA in serum (lower limit of quantitation < 40 IU/mL) were dosed for 24 weeks with follow up for 24 weeks.  Primary endpoint is > 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 follow-up.  Tenofovir or Entecavir was started prior to therapy.  Serial assessments of safety parameters, liver tests, pharmacokinetics, histology, and virologic (HDV RNA and HBV DNA) markers were collected.  LIFT is being conducted within the National Institutes of Health (NIH) at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
About Hepatitis Delta Virus (HDV)
Hepatitis Delta is caused by infection with the hepatitis delta virus and leads to the most severe form of viral hepatitis.  Hepatitis delta occurs only as a co-infection in individuals harboring hepatitis B virus (HBV).  Hepatitis delta leads to more severe liver disease than HBV alone and is associated with accelerated liver fibrosis, liver cancer, and liver failure.  Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not affect HBsAg and have no impact on HDV.
Hepatitis delta is a disease with a significant impact on global health, which may affect up to 15-20 million people worldwide.  The prevalence of HDV varies among different parts of the world.  Globally, HDV infection is reported to be present in approximately 4.3% to 5.7% of chronic Hepatitis B carriers.

StephenW

Eiger在2020數字國際肝臟大會（TM）的晚期斷路器會議上宣布Peginterferon Lambda-Lonafarnib聯合治療結果來自2期LIFT HDV研究的晚期治療
加利福尼亞州帕洛阿爾托，2020年8月31日，美國/美通社/-艾格生物製藥有限公司（Nasdaq：EIGR），致力於針對嚴重罕見和超罕見疾病的靶向，一流療法的開發和商業化，今天宣布了在2020年數字國際肝病大會上最新發布的海報結果，該結果顯示了LIFT 2期LIFT Lambda – Lonafarnib聯合研究對感染了肝炎三角洲病毒（HDV）的患者的治療結局。 LIFT（Lambda InterFeron聯合療法）研究正在美國國立糖尿病與消化暨腎病研究所（NIDDK）的國立衛生研究院（NIH）內進行。 Lambda是HDV（人類病毒性肝炎最嚴重的形式）臨床開發中的一流III型乾擾素。

NIDDK首席研究員克里斯托弗·柯說：“我們以前在NIDDK的多項研究中提出了令人鼓舞的結果，即Lonafarnib可以降低HDV感染患者的HDV RNA病毒載量。” “ Lambda和Lonafarnib聯合治療正在進行中的LIFT研究的治療結果在第24週結束時表示可能對HDV進行基礎聯合治療。我們將在將來介紹LIFT研究的第48週隨訪結果。”

LIFT是一項2a期開放標籤研究，研究對像是26名成年慢性HDV患者，每週接受Lambda 180 mcg聯合Lonafarnib 50 mg聯合利托那韋100 mg加強治療，每週兩次，持續24週。主要療效終點是治療結束時HDV RNA的> 2 log下降。中位數基線評估包括：ALT（64 IU / mL），AST（47 IU / mL），Ishak纖維化（3），改良的HAI炎症（9），HBV DNA（<20 IU / mL）和log HDV RNA（4.74 IU） / mL）。

在治療的第24週結束時，26名患者中的25名（96％）達到HDV RNA下降> 2 log的主要終點，58％的患者低於定量限或未檢測到，中位HDV RNA下降為3.2 log IU / mL（CI：2.50-3.93，p ＜0.0001）。在大多數患者中，對於慢性HDV患者，使用Lambda和Lonafarnib的聯合治療似乎可以耐受長達6個月。 LIFT治療的最終結果支持繼續探索HDV中的這種治療組合。

不良事件多為輕度至中度，包括胃腸道相關的副作用，體重減輕，高膽紅素血症和貧血。依照協議減少的劑量在3例患者中發生，並在4例患者中終止，這主要是由於已知的與聚乙二醇干擾素λ相關的副作用。

關於培根干擾素Lambda（Lambda）
Lambda是一種特徵明確的晚期晚期一流的III型乾擾素（IFN），可刺激免疫反應，這對於病毒感染期間宿主保護的發展至關重要。 Lambda靶向III型IFN受體，該受體不同於IFN alfa靶向的I型IFN受體，導致相同的Jak-STAT信號轉導級聯反應被激活。 Lambda III型受體在肝細胞中高度表達，而在造血和中樞神經系統細胞中表達有限，這可能會降低脫靶效應並提高Lambda的耐受性。

艾格峰（Eiger）從百時美施貴寶（Bristol-Myers Squibb）獲得了Lambda的全球版權。 Eiger正在開發Lambda作為單一療法，並與利托那韋加強的Lonafarnib聯合使用。 Lambda是研究人員，尚未獲得任何適應症的批准。艾格（Eiger）已獲得美國食品藥品管理局（FDA）和歐洲藥品管理局（EMA）的“孤兒”稱號，以及FDA為HDV中的Lambda獲得快速通道和突破性療法的稱號。

關於洛納法尼布
Lonafarnib是法尼基轉移酶的特徵鮮明，晚期，口服活性的同類抑製劑，法尼基轉移酶是一種通過稱為烯丙基化的過程參與蛋白質修飾的酶，該過程是HDV生命週期中的重要過程。阻斷大三角洲肝炎抗原（LDHAg）的異戊二烯化可減少HDV複製。

Lonafarnib已在國際學術中心的120多名受HDV感染的患者中使用，並處於第3期的一項國際，關鍵性臨床研究（D-LIVR研究）中。 Lonafarnib已被美國FDA和歐洲藥品管理局（EMA）授予“孤兒藥”稱號，被美國FDA授予“快速通道和突破性療法”稱號，並被EMA授予PRIME稱號。 Lonafarnib未經許可用於任何適應症，並已獲得默克·夏普（Merck Sharp＆Dohme Corp。）（在美國和加拿大以外被稱為MSD）的許可。
關於LIFT研究
LIFT（Lambda InterFeron聯合療法）是一項開放標籤的2期研究，評估了26名受HDV感染的患者中的Lambda + Lonafarnib + Ritonavir。對血清中可量化的HDV RNA（定量下限<40 IU / mL）的患者給藥24週，並隨訪24週。主要終點是治療結束時HDV RNA的> 2 log下降。次要終點包括隨訪結束時的組織學檢查（組織學活動指數提高2分以上且纖維化無進展）。在治療之前開始使用替諾福韋或恩替卡韋。收集安全性參數，肝試驗，藥代動力學，組織學和病毒學（HDV RNA和HBV DNA）標記的系列評估。 LIFT正在美國國立糖尿病與消化與腎臟疾病研究所（NIDDK）的國立衛生研究院（NIH）內進行。

關於肝炎三角洲病毒（HDV）
肝炎三角洲是由肝炎三角洲病毒感染引起的，並導致最嚴重的病毒性肝炎形式。乙型肝炎僅在合併乙型肝炎病毒（HBV）的個體中作為共同感染髮生。三角洲肝炎比單獨的HBV導致更嚴重的肝臟疾病，並與加速的肝纖維化，肝癌和肝衰竭有關。批准的HBV核苷酸治療只能抑制HBV DNA，不影響HBsAg，也不會對HDV產生影響。

三角洲肝炎是一種對全球健康產生重大影響的疾病，可能影響全球15-20百萬人。 HDV的患病率在世界各地有所不同。在全球範圍內，據報導HDV感染約佔慢性乙型肝炎攜帶者的4.3％至5.7％。