GSK's bepirovirsen, an antisense drug in development for chronic hepatitis B (CHB), has been granted fast-track designation by the U.S. Food and Drug Administration (FDA). This designation aims to expedite the review process for bepirovirsen, acknowledging its potential to address a critical unmet need in CHB treatment. The FDA's decision highlights bepirovirsen as the only single agent in phase 3 development that has demonstrated the potential to achieve a "functional cure" when used in conjunction with standard CHB therapies based on oral nucleoside or nucleotide analogue (NA) drugs.
Hepatitis B affects nearly 300 million people worldwide. While current NA treatments like Gilead's Viread (tenofovir) can manage the virus, a curative treatment remains elusive. A functional cure, defined as the clearance of hepatitis B surface antigen (HBsAg) from the blood with sustained undetectable levels post-treatment, is the ultimate goal. CHB can lead to severe liver complications, including cirrhosis and liver cancer, resulting in approximately one million deaths annually. Despite the availability of treatments, only a fraction of those infected are diagnosed and receive appropriate care, with estimates suggesting that only one in ten patients are diagnosed worldwide and just 5% receive treatment.
The fast-track designation was primarily based on data from the phase 2b B-Clear trial. Results from the B-Clear study indicated that bepirovirsen could reduce HBsAg levels below the limit of detection in approximately 10% of patients after 24 weeks of treatment. While this was a decrease from an earlier readout of almost 30%, GSK notes that it is still significantly higher than what is typically observed with the current standard of care. The B-Clear study also revealed that patients with lower baseline HBsAg levels were more likely to benefit from bepirovirsen treatment, with about 25% achieving undetectable levels of the biomarker. This suggests the possibility of targeting the drug to patients most likely to respond.
Ongoing Clinical Trials
GSK has initiated the phase 3 B-Well program to further evaluate bepirovirsen. Additionally, the company is conducting a long-term extension study to the B-Clear trial, named B-Sure, which will monitor patients for around three years to assess the durability of the treatment effect and long-term safety.
Market Potential
Analysts at William Blair have estimated that the market for a functional cure for hepatitis B could mirror that of hepatitis C virus, which peaked at around $10 billion per year. GSK projects peak sales of approximately £2 billion ($2.5 billion) for bepirovirsen, should it receive regulatory approval. GSK initially licensed bepirovirsen from Ionis in 2019, with an upfront payment of $25 million and potential milestone payments reaching up to $262 million.
Competition
Other therapies in development for CHB include Roche/Dicerna's xalnesiran and Arrowhead Pharma’s ARO-HBV.
