GSK Reports Full Phase 3 B-Well Results for Hepatitis B Drug Bepirovirsen

GSK said on May 28 that bepirovirsen, its investigational antisense medicine for chronic hepatitis B, met the main response goal in 19% of treated participants across two Phase 3 trials, according to the company's announcement. The full results of the B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820) trials were published in the New England Journal of Medicine and presented at the European Association for the Study of the Liver (EASL) congress, the company said.

GSK first reported in January that both trials had met their primary endpoint, ConsultantLive reported at the time, without releasing the figures. The May data give the rates for the first time.

The B-Well results

B-Well 1 and B-Well 2 are randomized, double-blind, placebo-controlled trials run in 29 countries. They enrolled adults with chronic hepatitis B who were already taking nucleos(t)ide analogue antiviral therapy and had a hepatitis B surface antigen (HBsAg) level of 3,000 IU/mL or less. Participants received six months of bepirovirsen or placebo on top of standard care.

The primary endpoint was what GSK calls "functional cure," defined as HBsAg not detected and hepatitis B virus DNA below the limit of quantification, sustained for at least 24 weeks after stopping all treatment. In pooled data, 233 of 1,220 bepirovirsen recipients (19%) met that endpoint, compared with 0 of 614 in the placebo groups, with p<0.001 in both trials, according to GSK.

In a key secondary endpoint, among participants with a baseline HBsAg level of 1,000 IU/mL or less, the response rate was 26% (200 of 768 versus 0 of 393 on placebo). In an exploratory analysis, 49% of bepirovirsen recipients had an HBsAg level of 100 IU/mL or less one year after the end of treatment, the company said.

GSK said the safety and tolerability profile was consistent with earlier studies of the drug. The most frequent adverse events were injection site redness, local pain and a temporary rise in a liver enzyme.

"For the first time, bepirovirsen offers the possibility of significantly better functional cure rates than the current standard of care," said Tony Wood, GSK's chief scientific officer. GSK says less than 1% of patients reach that outcome on current standard care, which typically requires lifelong therapy.

The drug and its review

Bepirovirsen is an antisense oligonucleotide designed to reduce production of hepatitis B virus RNA and proteins, lower HBsAg in the blood and stimulate the immune system. GSK licensed it from Ionis Pharmaceuticals in 2019, according to ConsultantLive.

The drug is under priority review by the FDA, where it holds breakthrough therapy and fast track designations, and is under review in Europe, Japan and China, GSK said. The company expects the first regulatory decisions in the third quarter of 2026. Bepirovirsen is not approved in any market.