Assembly Biosciences Reports Positive Phase 1b Results for Next-Generation Hepatitis B Capsid Assembly Modulator ABI-4334
核心洞察
Assembly Biosciences presented positive Phase 1b data for ABI-4334, a next-generation capsid assembly modulator targeting chronic hepatitis B infection, at the AASLD Liver Meeting.
The study demonstrated favorable safety and tolerability profiles with multi-log declines in HBV DNA (搜索) and pregenomic RNA (搜索) at both 150 mg and 400 mg doses over 28 days.
ABI-4334 achieved exposures multiple folds above levels required for inhibition of cccDNA (搜索) formation, supporting engagement of both CAM mechanisms of action.
Assembly Biosciences has unveiled promising Phase 1b clinical data for ABI-4334, its next-generation capsid assembly modulator (CAM) designed to treat chronic hepatitis B virus (HBV) infection. The data, presented at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting in Washington, D.C., demonstrated potent antiviral activity and favorable safety profiles in patients with chronic hepatitis B infection.
Study Design and Patient Population
The randomized, blinded Phase 1b study evaluated ABI-4334 in two cohorts of predominantly HBeAg-negative subjects with chronic hepatitis B infection not suppressed on nucleoside analogues. Patients received either 150 mg or 400 mg oral doses of ABI-4334 administered once-daily over 28 days.
Safety and Tolerability Profile
ABI-4334 demonstrated a favorable safety and tolerability profile at both dose levels evaluated in the study. The treatment was well tolerated across both the 150 mg and 400 mg dosing cohorts, with no significant safety concerns reported during the 28-day treatment period.
Antiviral Activity Results
The study revealed multi-log declines in both hepatitis B virus DNA and pregenomic RNA (搜索) (pgRNA) for both doses tested. These substantial reductions are consistent with the increased in vitro potency of ABI-4334 compared to first-generation CAMs, supporting full engagement of the first CAM mechanism of action through suppression of viral replication.
Notably, the study achieved exposures multiple folds above levels anticipated to be required for inhibition of cccDNA (搜索) formation, the second CAM mechanism of action, at both dose levels. This finding suggests ABI-4334's potential to target multiple aspects of HBV replication and persistence.
As expected in predominantly HBeAg-negative patients with a short dosing interval, reductions in HBsAg were not observed during the study period.
Clinical Significance and Development Strategy
"We are pleased to highlight positive data from our Phase 1b study for ABI-4334 with the scientific community," said Anuj Gaggar, MD, PhD, chief medical officer of Assembly Biosciences. "These data demonstrate the very high potency we set out to achieve for ABI-4334 and support its potential to maximize antiviral activity as a component of multi-drug combination regimens targeting cures for chronic hepatitis B infection."
The results support ABI-4334's development as a component of multi-drug combination regimens aimed at achieving functional cures for chronic hepatitis B infection, addressing a significant unmet medical need in the treatment landscape.
Partnership and Future Development
Under the collaboration agreement between Assembly Biosciences and Gilead Sciences, Gilead has the right to opt in to an exclusive license for further development and commercialization of ABI-4334 after reviewing an option data package following completion of this Phase 1b study. This partnership structure provides Assembly Biosciences with a potential pathway for advancing ABI-4334 through later-stage development with a major pharmaceutical partner.
ABI-4334 remains an investigational product candidate that has not been approved anywhere globally, and its safety and efficacy have not been established. The company continues to evaluate the compound's potential as part of its broader pipeline targeting serious viral diseases including herpesvirus, hepatitis B virus, and hepatitis delta virus infections.