The antisense oligonucleotide was even more effective in patients with relatively low viral activity. More than one-quarter of these individuals had undetectable levels of the virus in the blood for at least six months after stopping treatment.
GSK and Ionis Pharmaceuticals’ investigational antisense oligonucleotide led to a functional cure in almost one-fifth of treated patients with chronic hepatitis B infection.
That’s according to data from the Phase 3 B-Well 1 and B-Well 2 studies, which together enrolled 1,200 patients who were randomly assigned to be treated with the drug candidate bepirovirsen or placebo. All patients remained on background therapy with a nucleoside or nucleotide analogue, the current standard of care.
Results, disclosed in a news release Thursday morning, showed that across both B-Well studies, 19% of patients on bepirovirsen achieved functional cure, defined as having undetectable levels of the virus DNA and surface antigen in the blood for at least six months after stopping treatment. None of the placebo comparators met this bar.
Bepirovirsen’s benefits were stronger in patients who had relatively low viral activity (at most 1,000 U/L of the hepatitis B surface antigen), in whom 26% reached functional cure. According to GSK, around 45% of all patients with chronic hepatitis B fall under this category.
The findings were simultaneously published in The New England Journal of Medicine.
GSK and Ionis had previously toplined the B-Well trials, announcing in January that bepirovirsen yielded a “statistically significant and clinically meaningful functional cure rate” in patients—though the companies did not provide specific data at the time.
Nevertheless, William Blair in a Jan. 7 note argued that investors are probably underestimating the opportunity for bepirovirsen. “Buy-side expectations for the HBV program have been low,” the analysts wrote, contending that bepirovirsen “is likely an underappreciated opportunity” for Ionis. Gilead’s Vemlidy—an antiviral therapy for chronic hepatitis B—hit blockbuster status in 2025 with $1.07 billion in worldwide sales.
GSK has already filed for bepirovirsen’s approval and the FDA has designated the application for priority review. The drug is also under review in Japan and Europe, with the first regulatory verdicts expected to arrive in the third quarter. GSK is already gearing up for the drug’s launch, according to its Thursday release.
Bepirovirsen works by binding to the genetic material of the hepatitis B virus, in turn tagging it for destruction. Aside from preventing viral replication, bepirovirsen boosts the immune system’s activity, improving its ability to fight against the infection. GSK licensed the asset from Ionis in August 2019 for $25 million upfront plus up to $262 million in milestones.
