What clinops professionals need to know
The Phase II B-SUPREME trial is evaluating ALG-000184, a first-in-class oral capsid assembly modulator, in approximately 200 treatment-naïve adults with chronic hepatitis B, including both HBeAg-positive and HBeAg-negative patients. The study compares ALG-000184 monotherapy to tenofovir disoproxil fumarate over 48 weeks, with primary endpoints focused on HBV DNA suppression below quantifiable limits. Secondary measures include safety, pharmacokinetics, and changes in HBV antigen levels. Interim results are expected in 2026, and topline data in 2027. Earlier Phase I studies demonstrated sustained antiviral activity, favorable safety, and no new safety signals, supporting the therapy’s potential for improved long-term viral suppression.
Aligos Therapeutics has announced that dosing in the Phase II B-SUPREME clinical trial (NCT06963710) of its investigational ALG-000184 for the treatment of patients with chronic hepatitis B virus (HBV) infection has begun.1
Phase II B-SUPREME trial overview
The B-SUPREME study is a randomized, double-blind, active-controlled, multicenter trial enrolling approximately 200 treatment-naïve adults with chronic HBV infection, both HBeAg-positive and HBeAg-negative.
- Participants will receive either ALG-000184 monotherapy or tenofovir disoproxil fumarate for 48 weeks.
- The primary endpoint for HBeAg-positive patients is achieving HBV DNA below the lower limit of quantification (10 IU/mL) with target detected or target not detected.
- The primary endpoint for HBeAg-negative patients is achieving HBV DNA below the lower limit of quantification (10 IU/mL) with target not detected.
- Secondary and exploratory endpoints include safety, pharmacokinetics, and changes in HBV antigens and other virologic markers.
Aligos expects to have interim results in 2026, with topline data anticipated in 2027.
In a press release, Nezam Afdhal, MD, DSc, chief of gastroenterology, hepatology, and nutrition at Beth Israel Deaconess Medical Center and Charlotte & Irving Rabb Distinguished Professor of Medicine at Harvard Medical School, said: “Despite available treatments for chronic HBV infection, better therapies are needed to stem the progression to end-stage liver disease and liver cancer. I am pleased that therapies such as Aligos’ ALG-000184 are continuing to progress. The impressive antiviral activity seen in clinical trials to date provides hope for patients in need.”
Lawrence Blatt, PhD, MBA, chairman, president, and chief executive officer at Aligos Therapeutics, added: “Dosing the first subjects in our Phase II B-SUPREME study is an important milestone for Aligos. We are pleased by the engagement of the clinicians and subjects, as they recognize the need for improved treatment regimens for chronic HBV infection. We believe that ALG-000184 has first/best-in-class potential based on the exciting data seen across viral markers of HBV to date. We look forward to continuing to advance ALG-000184 for patients in need of better outcomes.”
Mechanism and prior study results
ALG-000184 is a potential first-in-class oral small molecule capsid assembly modulator (CAM-E). In October 2024, Aligos announced the FDA had cleared its Investigational New Drug (IND) for a Phase I Drug-Drug Interaction (DDI) study evaluating ALG-000184.2
The DDI study was designed to assess the effect of a cytochrome P450 inhibitor and inducer on ALG-000184 pharmacokinetics.
Earlier data of ALG-000184 showed:
- In single- and multiple-dose Phase I studies, ALG-000184 was well tolerated with no observed safety signals.
- The drug demonstrated linear pharmacokinetics and strong antiviral activity.
- Longer-term Phase I studies using ALG-000184 300 mg once daily for up to 96 weeks, with or without entecavir, showed sustained reductions in HBV DNA, HBV RNA, HBsAg, HBeAg, and HBcrAg.
Future data presentations
According to Aligos, Phase I 96-week dosing of ALG-000184 has been completed, and expects to share final and post-treatment follow up data at the American Association for the Study of Liver Disease’s The Liver Meeting in 2025.
In a press release from the time of when the IND designation was announced, Blatt said: “The acceptance of our third US IND is an important milestone for Aligos. This IND clearance allows us to begin the next stages of our clinical development for ALG-000184, including the advancement of the compound into Phase II clinical trials. ALG-000184 is the first novel, oral drug candidate for the treatment of HBV infection that can inhibit multiple components of the viral lifecycle, leading to more complete suppression of the virus compared to other therapeutic modalities.”
References
1. Aligos Therapeutics Announces First Subject Dosed in the Phase 2 B-SUPREME Study of ALG-000184 in Subjects with Chronic HBV Infection. News release. August 13, 2025. Accessed August 14, 2025. https://investor.aligos.com/news-releases/news-release-details/aligos-therapeutics-announces-first-subject-dosed-phase-2-b
2. Aligos Therapeutics Announces U.S. FDA Clearance of IND Application for ALG-000184. News release. October 22, 2024. Accessed August 14, 2025. https://investor.aligos.com/news-releases/news-release-details/aligos-therapeutics-announces-us-fda-clearance-ind-application
