2021 年 9 月 1 日Assembly Bio 宣布決定停止 ABI-H2158 的臨床開發

StephenW

Assembly Bio 宣布決定停止 ABI-H2158 的臨床開發2021 年 9 月 1 日 16:02 ET |資料來源：Assembly Biosciences, Inc.    ...--在第 2 階段研究中觀察到丙氨酸轉氨酶 (ALT) 水平升高後做出決定--公司將專注於推進正在進行的三重組合研究和早期管道候選者加利福尼亞州南舊金山，2021 年 9 月 1 日（全球新聞通訊社）--Assembly Biosciences, Inc.（納斯達克股票代碼：ASMB）是一家臨床階段的生物技術公司，開發針對乙型肝炎病毒 (HBV) 的創新療法，今天宣布了其決定在正在進行的 2 期試驗中觀察到 ALT 水平升高與藥物誘導的肝毒性一致後，停止開發 ABI-H2158 (2158)。“患者安全始終是我們的首要任務，這就是我們選擇停止開發 2158 的原因，”Assembly Bio 首席執行官兼總裁、醫學博士、AO 約翰麥克哈奇森說。 “我們仍然致力於為慢性乙型肝炎患者開發有限的治愈性療法，我們的戰略保持不變。我們將繼續評估我們的核心抑製劑組合，最終選擇最好和最安全的候選藥物進行後期臨床試驗，因為我們相信這種機制將成為未來治愈方案的重要和關鍵組成部分。我們仍然專注於快速推進我們的其他臨床項目，包括兩項正在進行的 2 期三聯聯合研究，加速 3733 和 4334 的臨床開發，以及推進我們 HBV 產品組合中具有互補機制的其他研究項目。而且，與往常一樣，我們將繼續評估戰略機會，以在公司的管道中創造額外價值。”2158 的 2 期臨床研究是一項多中心、隨機、安慰劑對照試驗，針對 HBeAg 陽性或 HBeAg 陰性慢性乙型肝炎感染但無肝硬化的初治患者。共有 88 名患者被納入並隨機三比一接受 300 毫克 2158 加恩替卡韋或安慰劑加恩替卡韋，每天一次，持續長達 72 週。在該研究中，兩名接受 2158 治療的患者出現了 4 級 ALT 升高，導致停藥。另外兩名接受 2158 治療的患者出現了 3 級 ALT 升高。尚未確定 ALT 升高的其他原因，這四名患者繼續受到密切監測。該公司已與美國食品和藥物管理局 (FDA) 溝通了調查結果，並自願選擇停止開發 2158 和第 2 期研究。在將公司的決定傳達給 FDA 後，FDA 指出，2158 也將被置於臨床擱置狀態。Assembly Bio 保持著深入的研究核心抑製劑候選藥物管道。最先進的核心抑製劑候選藥物 vebicorvir (VBR) 已在第 2 階段計劃中治療長達 1.5 年的患者中顯示出良好的安全性和有效的抗病毒特性。 VBR 正在兩項正在進行的三聯聯合研究中進行評估，預計初始治療數據將在 2022 年進行。 ABI-H3733 (3733) 已完成其 1a 期研究，初始數據計劃在即將舉行的醫學會議上公佈。此外，該公司預計將在 2022 年將其最近選定的核心抑製劑候選藥物 ABI-4334 (4334) 推進臨床開發。4334 具有一流的臨床前概況，對新病毒的產生具有個位數的納摩爾效力，如以及共價閉合環狀 DNA (cccDNA) 的形成。重要的是，3733 和 4334 在結構上與 2158 不同。Assembly Bio 還將繼續推進一系列項目，重點關注核心抑制之外的 HBV 抗病毒機制。與 Door Pharma 合作，Assembly Bio 正在開發一類新型 HBV 核心蛋白調節劑，該調節劑有可能干擾病毒核酸，包括 cccDNA 轉錄。此外，該公司正在進行針對兩個新目標的專有內部研究計劃。通過重新分配公司之前為 2158 項目及其第 2 階段研究預留的資源，Assembly Bio 預計能夠更快地推進其下一代資產的開發，同時將其現金跑道延長至 2023 年下半年。

StephenW

Assembly Bio Announces Decision to Discontinue Clinical Development of ABI-H2158

September 01, 2021 16:02 ET | Source: Assembly Biosciences, Inc.

    ...

--Decision follows observation of elevated alanine transaminase (ALT) levels in Phase 2 study
--Company will focus on advancing ongoing triple combination studies and earlier pipeline candidates

SOUTH SAN FRANCISCO, Calif., Sept. 01, 2021 (GLOBE NEWSWIRE) -- Assembly Biosciences, Inc. (Nasdaq: ASMB), a clinical-stage biotechnology company developing innovative therapeutics targeting hepatitis B virus (HBV), today announced its decision to discontinue development of ABI-H2158 (2158) following the observation of elevated ALT levels consistent with drug-induced hepatotoxicity in an ongoing Phase 2 trial.

“Patient safety is always our priority, which is why we have elected to discontinue the development of 2158,” said John McHutchison, AO, MD, chief executive officer and president of Assembly Bio. “We remain committed to our pursuit of developing finite and curative therapies for individuals with chronic hepatitis B, and our strategy remains unchanged. We will continue to evaluate our core inhibitor portfolio, to ultimately choose the best and safest candidate to take forward into later stage clinical trials as we believe this mechanism will be an important and key component of future curative regimens. We remain focused on expeditiously advancing our additional clinical programs, including the two ongoing Phase 2 triple combination studies, accelerating the clinical development for 3733 and 4334, and progressing additional research programs in our HBV portfolio with complementary mechanisms. And, as always, we will continue evaluating strategic opportunities to build additional value in the company’s pipeline.”

The Phase 2 clinical study for 2158 is a multi-center, randomized, placebo-controlled trial in treatment-naïve patients with HBeAg positive or HBeAg negative chronic hepatitis B infection without cirrhosis. A total of 88 patients were enrolled and randomized three-to-one to receive either 300 mg 2158 plus entecavir or placebo plus entecavir once daily for up to 72 weeks. In the study, two patients receiving 2158 experienced Grade 4 elevations in ALT leading to drug discontinuation. Two additional patients also receiving 2158 developed Grade 3 ALT elevations. No alternate causes for the ALT elevations have been identified, and these four patients continue to be closely monitored. The company has communicated the findings with the U.S. Food & Drug Administration (FDA) and has voluntarily chosen to discontinue development of 2158 and the Phase 2 study. After communicating the company’s decision to the FDA, the FDA noted that 2158 would also be placed on clinical hold.

Assembly Bio maintains a deep pipeline of investigational core inhibitor candidates. The most advanced core inhibitor candidate, vebicorvir (VBR), has demonstrated favorable safety and a potent antiviral profile in patients treated for up to 1.5 years in the Phase 2 program. VBR is being evaluated in two ongoing triple combination studies for which initial on-treatment data are anticipated during 2022. ABI-H3733 (3733) has completed its Phase 1a study and initial data is planned to be announced at an upcoming medical meeting. Additionally, the company expects to advance its recently-selected core inhibitor candidate ABI-4334 (4334) into clinical development in 2022. 4334 has a best-in-class preclinical profile with single-digit nanomolar potency against the production of new virus, as well as the formation of covalently closed circular DNA (cccDNA). Importantly, 3733 and 4334 are structurally distinct from 2158.

Assembly Bio will also continue to advance a research pipeline of programs focusing on HBV antiviral mechanisms beyond core inhibition. In a collaboration with Door Pharma, Assembly Bio is developing a novel class of HBV core protein modulators that have the potential to interfere with viral nucleic acid including cccDNA transcription. Additionally, the company has proprietary internal research programs underway for two novel targets.

By redirecting the company’s resources previously reserved for the 2158 program and its Phase 2 studies, Assembly Bio expects to be able to advance development of its next-generation assets more quickly, while simultaneously extending its cash runway into the second half of 2023.