GSK eyes October FDA verdict on chronic hep B drug

GSK's antisense-based drug for chronic hepatitis B (CHB), bepirovirsen, has started a speedy FDA review that should deliver a verdict by 26th October.

If approved, bepirovirsen – which has priority, fast-track, and breakthrough designations from the US regulator – will become a first-in-class new treatment for CHB, a major health challenge that affects over 250 million people worldwide.

The review is based on the results of the B-WELL 1 and B-WELL 2 studies, which showed that bepirovirsen was able to achieve a statistically higher functional cure rate than placebo when added to standard care for CHB.

Bepirovirsen targets hepatitis B virus (HBV) messenger RNA (mRNA) and pregenomic RNA (pgRNA), tagging them to be denatured by cellular enzymes, which in turn interrupts the virus' ability to replicate itself and helps the patient's immune system to re-establish control of the infection.

In the B-WELL studies, significantly more patients treated with the antisense oligonucleotide (ASO) were able to clear a biomarker called hepatitis B surface antigen (HBsAg) from their blood and have it remain undetectable for at least 24 weeks after stopping treatment.

While not a complete cure that eradicates HBV from the body, achieving a functional cure is associated with a significant reduction in the risk of long-term liver complications, including liver cancer, as well as all-cause mortality.

CHB is the leading cause of liver cancer, accounting for more than half (56%) of all cases, and is implicated in around 1.1 million deaths a year worldwide.

GSK noted that the current standard of care – typically with nucleoside or nucleotide analogue drugs, such as Gilead's polymerase inhibitor Viread (tenofovir) – often requires lifelong therapy and functional cure rates remain low at around 1%. The company has high hopes for bepirovirsen, modelling peak sales of around £2 billion a year, which would make it a big contributor to the company's target of driving annual revenues above £40 million by 2031.

GSK is also running a long-term extension to the phase 2 B-Clear study, called B-Sure, which will follow patients for around three years and is due to report results in 2029.

Meanwhile, its pipeline includes a gene-editing ASO-based regimen for CHB called GSK5637608 (daplusiran and tomligisiran), licensed from Johnson & Johnson in 2023 and in phase 2, and a PAPD5/PAPD7 inhibitor (GSK3965193) in phase 1.

Analysts at William Blair have previously suggested that the market for an HBV cure could be around the same size as for hepatitis C virus (HCV), which peaked at around $10 billion a year and was dominated by Gilead drugs. However, that proved a short-lived bonanza, with sales falling sharply as the pool of eligible chronic hepatitis C patients reduced.