Aligos has enrolled 144 patients into its Phase 2 B-SUPREME study of pevifoscorvir sodium (ALG-000184) in chronic hepatitis B, hit both interim analysis triggers, and remains on a 2027 timeline for topline data. The first interim, covering about 60% (36 of 60) of the HBeAg-negative cohort after 12 weeks of therapy, is slated for the first half of 2026. A second interim, when roughly half (55 of ~110) of the HBeAg-positive cohort completes 24 weeks, is expected in the back half of 2026. In parallel, the company disclosed the resignation of its chief medical officer and initiated a search for a successor.
The randomized, double-blind, active-controlled multicenter trial compares pevifoscorvir monotherapy to tenofovir disoproxil fumarate over 48 weeks in approximately 200 untreated adult HBeAg-positive and -negative patients. The primary endpoint is virologic suppression to below 10 IU/mL, with target detected or not detected in HBeAg-positive patients and target not detected in HBeAg-negative patients. The protocol builds in Data Safety Monitoring Board oversight and the option for sample size re-estimation at each interim while keeping the sponsor blinded to subject-level data.
Strategically, Aligos is leaning into a pragmatic, chronic-suppressive path with a capsid assembly modulator as monotherapy, rather than pursuing a finite, functional-cure thesis through complex combinations. That choice lowers operational burden and regulatory variables versus multi-agent regimens, but it raises a differentiation bar against low-cost nucleotide analogs. Tenofovir already delivers high rates of DNA suppression; to justify a shift in standard practice, pevifoscorvir will need to show faster and deeper virologic knockdown and convincing antigen reductions on secondary endpoints such as HBsAg and HBcrAg, not simply non-inferiority on DNA at week 48. The interim-enabled option to resize the trial is a hedge against effect-size uncertainty in a comparator landscape where marginal gains are hard to prove and harder to commercialize.
For sites and CROs, the design concentrates operational risk in assay rigor and timing. Central-lab consistency to a 10 IU/mL LLOQ and clear adjudication of target detected versus target not detected will determine endpoint credibility. The 12- and 24-week interim clocks compress data cleaning and query turnaround, requiring close coordination on visit scheduling, lab logistics, and DSMB packet readiness. Any sample size re-estimation or protocol refinement after interims could cascade into budget re-sets, contract amendments, and recruitment adjustments across regions. Drug accountability and adherence monitoring over a 48-week blinded period will be scrutinized, given the monotherapy positioning.
The CMO transition mid-study adds execution and regulatory relationship risk. Continuity across medical monitoring, safety signal interpretation, and dialogue with FDA, EMA, and NMPA will matter if interims prompt design changes or if the program advances to Phase 3. Maintaining steady site engagement and preserving operational tempo through leadership change should be a near-term priority.
What to watch next are the qualitative signals from the DSMB: any recommendation to resize the study, comments on safety tolerability including ALT flares, and early trajectories in DNA and antigen decline. Absent a strong antigen story, payers and guideline bodies may view another chronic oral suppressive agent as incremental versus tenofovir. A positive interim could firm up a Phase 3 path in 2027; a flat read could push Aligos toward combination strategies or co-formulation. The operational tell will be whether the company moves quickly on protocol updates and leadership stabilization ahead of the second interim window.
