GSK posts latest data showing bepirovirsen producing functional cure for up to 19% of hep B patients

GSK (NYSE: GSK) has reported pivotal Phase III data showing that bepirovirsen, its antisense oligonucleotide (ASO) for chronic hepatitis B, achieved functional cure in 19% of treated patients versus 0% on standard of care alone. The result indicate that bepirovirsen is on course to become the first therapy capable of delivering meaningful functional cure rates if gaining market approval, in a disease affecting more than 240 million people worldwide. Bepirovirsen is currently under FDA Priority Review following NDA acceptance in April 2026, with a PDUFA date of October 26, 2026.

Pooled results from the randomized, double-blind, placebo-controlled B-Well 1 and B-Well 2 trials enrolled 1,834 nucleos(t)ide analogue (NUC)-treated adults with chronic hepatitis B and baseline hepatitis B surface antigen (HBsAg) ≤3,000 IU/mL across 29 countries. Both arms received background standard of care; the treatment arm added six months of bepirovirsen. The primary endpoint — functional cure, defined as undetectable HBsAg and HBV DNA below the limit of quantification for at least 24 weeks after stopping all treatment — was assessed at week 72. In the overall population, 19% of bepirovirsen recipients (233 of 1,220) achieved functional cure versus 0% on placebo (p < 0.001 in both trials). In patients with baseline HBsAg ≤ 1,000 IU/mL, a group representing roughly 45% of diagnosed chronic hepatitis B cases globally, the functional cure rate reached 26% (200 of 768 versus 0 of 393; p < 0.001). An exploratory analysis found that 49% of bepirovirsen recipients achieved quantitative HBsAg of ≤100 IU/mL one year after end of treatment, a threshold associated in the medical literature with increased immune control.

The safety profile was consistent with prior bepirovirsen studies; the three most common adverse events were injection site erythema, local pain, and a transient rise in liver enzyme levels.

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Bepirovirsen works by binding all HBV mRNA transcripts and promoting their degradation via RNase H-mediated cleavage, reducing viral protein expression including HBsAg and stimulating immune-mediated control. The chronic hepatitis B treatment landscape has long been dominated by oral NUCs — including Gilead Sciences’ Vemlidy (tenofovir alafenamide) and Bristol Myers Squibb’s Baraclude (entecavir) — which suppress viral replication effectively but rarely achieve HBsAg loss, with functional cure rates below 1% annually. Roche’s Pegasys (peginterferon alfa-2a) offers finite-duration therapy with modestly higher HBsAg loss rates but carries tolerability limitations.

Among pipeline agents, Johnson & Johnson’s JNJ-3989, an RNAi therapeutic targeting HBV mRNAs, has demonstrated HBsAg reductions in Phase II, though functional cure data at the scale of B-Well have not been reported. Cross-trial comparisons are limited by differences in patient populations, baseline viral activity, and endpoint definitions. Bepirovirsen is currently under priority review by the US FDA, with Breakthrough Therapy and Fast Track designations; regulatory reviews are also under way in the EU, Japan, and China, with first decisions anticipated in Q3 2026.


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