Assembly Biosciences announced positive topline results from a Phase 1b study of ABI-4334, a next-generation capsid assembly modulator (CAM), in patients with chronic hepatitis B (HBV). The 400 mg dose showed similar antiviral activity to the 150 mg dose over 28 days, suggesting saturation of viral replication inhibition at the lower dose. The trial completion triggers an opt-in decision point for Gilead Sciences regarding further development and commercialization of ABI-4334.
These findings represent a potentially significant advancement in HBV treatment. Current therapies rarely cure chronic HBV, leaving patients at risk of long-term complications like cirrhosis and liver cancer. ABI-4334’s dual mechanism of action, inhibiting both viral replication and the formation of the viral reservoir (cccDNA), offers a potential pathway to a functional cure, a significant unmet need. The confirmation that the lower 150mg dose achieves saturated inhibition of viral replication is also crucial, as it allows for the potential use of higher doses (such as the 400mg dose tested) to focus on inhibiting cccDNA formation without compromising efficacy against viral replication. This strategic dosing flexibility may enhance the chances of achieving a functional cure.
Both the 150 mg and 400 mg doses demonstrated potent antiviral activity, with mean HBV DNA reductions of 2.9 and 3.2 log10 IU/mL, respectively. The drug also exhibited a favorable safety and tolerability profile in both cohorts, supporting once-daily oral dosing. Pharmacokinetic data confirmed that both doses achieved plasma concentrations significantly exceeding the levels required for antiviral activity and cccDNA formation inhibition.
The positive Phase 1b results and Gilead’s impending opt-in decision mark a pivotal moment for ABI-4334 and the HBV field. A positive decision from Gilead could propel ABI-4334 into later-stage clinical trials, bringing this promising therapeutic closer to patients and potentially reshaping the HBV treatment landscape. A combination therapy approach, leveraging ABI-4334’s unique mechanism, may ultimately prove crucial in achieving a functional cure for chronic HBV.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
