Bepirovirsen Delivers a Functional Cure in About One in Five Chronic Hepatitis B Patients in Phase 3 Trials
GSK's antisense drug bepirovirsen cleared chronic HBV in 20% and 19% of patients across two Phase 3 trials, versus none on placebo, the NEJM reports.
Overview
An investigational drug from GSK cleared chronic hepatitis B in roughly one in five treated patients across two large Phase 3 trials, a result that, if confirmed by regulators, would mark the first oral-and-injectable regimen to push meaningful numbers of patients toward a so-called functional cure rather than indefinite suppression. According to Healio, 20% of the bepirovirsen group achieved functional cure at week 72 in the trial known as B-Well 1, as did 19% in B-Well 2, while no patients in the placebo groups achieved functional cure. The results were simultaneously presented at the EASL Congress and published in The New England Journal of Medicine in June 2026.
What We Know
Bepirovirsen is an investigational antisense oligonucleotide that targets HBV transcripts and reduces levels of HBV DNA and HBsAg, Healio reported. CIDRAP describes the mechanism in more detail: the drug can achieve a functional cure — when the virus becomes undetectable without continuous therapy — by breaking down HBV RNA, inhibiting viral replication, and priming the immune system. GSK co-developed the drug.
The program comprised two replicate, randomized, placebo-controlled Phase 3 trials, B-Well 1 and B-Well 2, enrolling 1,838 adults with noncirrhotic chronic HBV infection across 29 countries in Europe, the Asia-Pacific region, and the Americas, according to CIDRAP. Patients were randomly assigned in a 2:1 ratio to receive 300 mg of bepirovirsen or placebo as weekly subcutaneous injections over 24 weeks, per Healio, with the primary endpoint assessed at week 72.
The headline efficacy numbers were consistent across the two trials. In B-Well 1, 127 of 650 patients (20%) in the bepirovirsen arm reached functional cure versus 0 of 328 on placebo; in B-Well 2, 106 of 570 patients (19%) responded versus 0 of 286 on placebo, CIDRAP reported. Response was more common in patients who started with lower viral antigen levels: among those with baseline HBsAg of 1,000 IU/mL or less, functional cure rates reached 25% in B-Well 1 and 28% in B-Well 2, according to Healio.
Why It Matters
Chronic hepatitis B is one of the largest unsolved problems in infectious disease. The World Health Organization estimates that 240 million people were living with chronic hepatitis B infection in 2024, with 0.9 million new infections each year and an estimated 1.1 million deaths, mostly from cirrhosis and hepatocellular carcinoma. Existing antiviral therapy suppresses the virus but rarely eliminates it, and the WHO notes that most people who start hepatitis B treatment must continue it for life.
That lifelong-therapy reality is what makes a functional cure — durable loss of the surface antigen without ongoing drugs — the field’s central goal. A regimen that delivers it in roughly a fifth of patients after a finite course of injections, and in more than a quarter of those with lower baseline antigen, would represent a categorical shift from the suppression-only standard rather than an incremental gain.
Safety
The trials reported a tolerability profile weighted toward injection-related and liver-enzyme effects. Across the bepirovirsen group, 91% of patients experienced adverse events, with 7% classified as serious, and the predominant grade 3 adverse event was elevated alanine aminotransferase, occurring in 6% of patients, Healio reported. CIDRAP reported that 16% of bepirovirsen recipients had adverse events of grade 3 or higher, versus 3% of the placebo group, and that adverse events led to discontinuation of treatment in 3% of the bepirovirsen group. Transient liver-enzyme elevations are a known feature of HBV therapies that provoke an immune response against the virus, and the data place that pattern in the foreground for clinicians weighing the regimen.
What We Don’t Know
The published results establish week-72 outcomes but leave open how durable the functional cures prove over longer follow-up, and what fraction of responders eventually relapse. The trials excluded patients with cirrhosis, so the regimen’s performance in more advanced liver disease is not addressed by these data. Neither the regulatory timeline nor any pricing has been resolved by the trial readout itself; a functional cure achieved in about one in five patients still leaves the large majority on the existing suppression-only standard, and the publications do not characterize which patients beyond the low-antigen subgroup are most likely to benefit.
The Machine Herald has tracked adjacent developments in viral hepatitis, including the FDA’s accelerated approval of Gilead’s Hepcludex for chronic hepatitis delta, a distinct virus that depends on co-infection with hepatitis B. Bepirovirsen’s target is the far larger chronic hepatitis B population itself, and its Phase 3 readout will now move the cure question from proof-of-concept toward a regulatory decision.