FDA Grants Fast Track Designation to Bepirovirsen for Chronic Hepatitis B

The FDA has granted fast track designation to bepirovirsen (GSK) for the treatment of chronic hepatitis B (CHB), according to a press release from GSK. Bepirovirsen is a triple action investigational antisense oligonucleotide and is being evaluated in the B-Well phase 3 clinical trial program for the treatment of CHB.¹

According to the World Health Organization (WHO), approximately 296 million individuals had CHB infections globally in 2019, with approximately 1.5 million new infections every year.² Additionally, in 2019, approximately 820,000 deaths were caused by hepatitis B infections that resulted in cirrhosis and hepatocellular carcinoma, according to the WHO.

The submission for fast track designation included the drug’s potential to address unmet medical needs for CHB, supported by data in 2 phase 2b trials: B-Clear and B-Sure. The trial evaluated the efficacy, safety, and durability of bepirovirsen, according to the press release. Currently, the drug is the only single agent in phase 3 development that has the potential to achieve a clinically meaningful cure response when combined with oral nucleoside/nucleotide analogues as demonstrated by the clinical trials.¹

The results of the B-Clear trial, published in the New England Journal of Medicine, showed that those with low baseline levels of hepatitis B surface level antigens were the most likely to benefit from the drug.^1,3

Individuals in group 1 received the drug as weekly subcutaneous injections at a dose of 300 mg for 24 weeks; group 2 received the drug at a dose of 300 mg for 12 weeks and then 150 mg for 12 weeks; group 3 received the drug at 300 mg for 12 weeks and then the placebo for 12 weeks; and group 4 received the placebo for 12 weeks and then the drug at 300 mg for 12 weeks, according to the study authors. Groups 1 through 3 also received loading doses.³ The study authors also indicated that 227 received nucleoside/nucleotide analogues and 230 did not.

Investigators used hepatitis B surface antigen levels below the limits of the quantification maintained for 24 weeks and after the end of treatment without a new initiation of antiviral medications as the composite primary endpoint, according to the study authors.³

For those who received the nucleoside/nucleotide analogues therapy, the primary outcome occurred in 9% of individuals in group 1, 9% in group 2, 3% in group 3, and 0% in group 4, according to the results. For those not receiving nucleoside/nucleotide analogues therapy, 10% achieved the primary outcome in group 1, 6% in group 2, 1% in group 3, and 0% in group 4.³

During weeks 1 and 12, adverse events (AEs) included injection-site reaction, pyrexia, fatigue, and increased alanine aminotransferase levels, according to the results of the study. AE rates occurred more commonly in the study drug groups (1, 2, and 3) compared with the placebo group (4).³

The study authors called for larger and longer trials to assess the efficacy and safety of bepirovirsen even more.³ It is also being investigated as a potential backbone therapy in future regimes for a broader population experiencing CHB, according to the press release.¹

References

1. GSK receives US FDA Fast Track designation for bepirovirsen in chronic hepatitis B. News release GSK. February 12, 2024. Accessed February 12, 2024. https://www.gsk.com/en-gb/media/press-releases/gsk-receives-us-fda-fast-track-designation-for-bepirovirsen-in-chronic-hepatitis-b/
2. World Health Organization. Hepatitis B. July 18, 2023. Accessed February 12, 2024. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b
3. Yuen MF, Lim SG, Plesniak R, Tsuji K, et al. Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. N Engl J Med. 2022;387(21):1957-1968. doi:10.1056/NEJMoa2210027