Assembly Biosciences has discontinued the clinical development of ABI-H2158, an investigational hepatitis B virus therapy, after elevated alanine transaminase (ALT) levels consistent with drug-induced hepatotoxicity were observed in a phase 2 trial.
ABI-H2158 is part of an investigational class of core inhibitors that are designed to disrupt the viral replication cycle. The multicenter, randomized, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT04398134) was evaluating the effects of ABI-H2158 in 88 treatment-naïve patients with HBeAg (hepatitis B e antigen) positive or HBeAg negative chronic hepatitis B infection without cirrhosis. Patients were randomly assigned 3:1 to receive either ABI-H2158 or placebo, in addition to entecavir, for up to 72 weeks.
During the study, 2 patients treated with ABI-H2158 developed grade 4 elevations in ALT leading to drug discontinuation. Two other patients treated with ABI-H2158 developed grade 3 ALT elevations. No alternative causes for the ALT elevations could be identified.
The Company has voluntarily chosen to discontinue the phase 2 study as well as the development of ABI-H2158. Subsequently, the Food and Drug Administration (FDA) placed ABI-H2158 on clinical hold.
“Patient safety is always our priority, which is why we have elected to discontinue the development of [ABI-H2158],” said John McHutchison, AO, MD, CEO and president of Assembly Bio. “[…] 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.”
The Company is currently evaluating other investigational core inhibitor candidates, including vebicorvir (ABI-H0731) for the treatment of chronic hepatitis B virus.
Assembly Bio announces decision to discontinue clinical development of ABI-H2158. News release. Assembly Biosciences, Inc. September 1, 2021. https://www.globenewswire.com/news-release/2021/09/01/2290389/16259/en/Assembly-Bio-Announces-Decision-to-Discontinue-Clinical-Development-of-ABI-H2158.html.