Aligos Therapeutics has initiated its Phase 2 B-SUPREME trial of ALG-000184, an oral capsid assembly modulator (CAM-E), in patients with chronic hepatitis B (HBV). The study will compare ALG-000184 monotherapy to tenofovir disoproxil fumarate in approximately 200 untreated HBeAg-positive and HBeAg-negative adults with chronic HBV over 48 weeks. Primary endpoints are HBV DNA levels below the lower limit of quantitation (LLOQ), targeting undetectable levels in both HBeAg groups.
This Phase 2 initiation represents a significant step for Aligos in a competitive HBV treatment landscape where functional cures remain elusive. The company is betting on ALG-000184’s potential for best-in-class efficacy based on promising Phase 1 data showing sustained reductions across multiple viral markers, including HBV DNA, RNA, and surface antigens. Direct comparison against tenofovir, a standard-of-care nucleoside analog, allows Aligos to benchmark ALG-000184’s performance against an established treatment and demonstrate potential advantages in achieving functional cures.
The trial design reflects the growing emphasis on functional cure as the key target for HBV therapies. While current treatments suppress viral replication, they rarely eliminate the virus, necessitating long-term therapy and leaving patients at risk for disease progression. ALG-000184’s mechanism, aimed at disrupting viral capsid formation, offers a distinct approach that could complement or even supersede existing nucleoside/nucleotide analog therapies. This strategy aligns with broader industry efforts to develop combination regimens that target multiple stages of the HBV lifecycle.
For sites and CROs, the B-SUPREME trial’s complex endpoint criteria, including LLOQ and HBeAg status stratification, present operational challenges. Achieving accurate and consistent HBV DNA measurements at very low levels requires specialized laboratory capabilities. Patient recruitment and retention will also be crucial given the 48-week duration and the availability of alternative treatment options. The study’s success could influence how future HBV trials are designed and executed, particularly regarding the assessment of functional cure.
Interim data are expected in 2026, and topline results in 2027. These results will be critical for Aligos’ future strategy, determining whether ALG-000184 can advance to Phase 3 and potentially challenge the current HBV treatment paradigm. Market acceptance will hinge not only on demonstrating superior efficacy but also on establishing a favorable safety and tolerability profile compared to existing options, particularly given the long-term nature of HBV treatment. The company will also need to navigate potential pricing and reimbursement hurdles if ALG-000184 is positioned as a premium-priced therapy. Ultimately, the B-SUPREME trial represents a key test of whether CAM-E therapy can deliver on its promise to transform HBV treatment and move the field closer to a functional cure.
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.
