Assembly Biosciences' investigational capsid assembly modulator (CAM), ABI-4334, has shown encouraging interim results in a Phase 1b trial for chronic hepatitis B virus (HBV) infection. The study, evaluating the safety, pharmacokinetics, and antiviral activity of ABI-4334, demonstrated a significant mean decline in HBV DNA levels in participants receiving a 150 mg oral, once-daily dose over a 28-day treatment period.
The trial, identified as ABI-4334-102 (NCT06384131) on clinicaltrials.gov, is a randomized, blinded, placebo-controlled, dose-ranging study. It enrolled treatment-naive or off-treatment participants with HBeAg positive or negative chronic HBV infection. The first cohort, receiving 150 mg of ABI-4334, showed a mean decline in HBV DNA of 2.9 log10 IU/mL. Among participants with detectable HBV RNA at baseline, a mean decline of 2.5 log10 U/mL for HBV RNA was observed.
Safety and Tolerability
Safety data from both the 150 mg and 400 mg cohorts indicated that ABI-4334 was well-tolerated, with a favorable safety profile. No serious adverse events or adverse events leading to study drug discontinuation were reported. Two grade three lab abnormalities, one alanine aminotransferase (ALT) elevation and one total bilirubin elevation, were observed in the 150 mg cohort, but both resolved with continued dosing of ABI-4334 or placebo.
Pharmacokinetic Profile
ABI-4334 exhibited a half-life supportive of once-daily oral dosing. Furthermore, pharmacokinetic data from the 150 mg cohort and preclinical studies showed that daily minimum plasma trough concentrations (Cmin) at the 150 mg dose achieved double-digit multiples over protein-adjusted EC50 for both antiviral activity and cccDNA formation.
Future Development
Enrollment is ongoing for the second cohort, which is evaluating a 400 mg oral once-daily dose of ABI-4334. Assembly Bio anticipates releasing data from this cohort in the first half of 2025. Under a collaboration agreement with Gilead Sciences, Inc., Gilead has the option to further develop and commercialize ABI-4334 after Assembly Bio delivers a data package following completion of this Phase 1b study.
Expert Commentary
"We are pleased to see strong antiviral activity in this first Phase 1b cohort for ABI-4334, our most potent CAM," said Anuj Gaggar, MD, PhD, chief medical officer of Assembly Bio. "While this is an early read, these interim data reinforce the potential of ABI-4334 to achieve our target clinical profile."
