--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
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.
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