FDA Grants Bepirovirsen Breakthrough Therapy Designation, Priority Review for Chronic Hepatitis B

The US Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for bepirovirsen, an investigational antisense oligonucleotide (ASO) developed by GSK in partnership with Ionis Pharmaceuticals, for the treatment of adults with chronic hepatitis B (CHB).

The Agency has simultaneously granted bepirovirsen Breakthrough Therapy designation and established a PDUFA target action date of October 26, 2026. If approved, bepirovirsen would represent the first therapy to achieve clinically meaningful functional cure rates in this population, addressing a significant gap in the current treatment landscape.

"Over one million people in the U.S. are living with chronic hepatitis B and as of today, require lifelong antiviral therapy to suppress the virus," Brett Monia, PhD, chief executive officer of Ionis Pharmaceuticals, said in a statement. "As the first medicine to deliver clinically meaningful functional cure rates, bepirovirsen is uniquely positioned to effectively treat CHB based on its potential to reduce the replication of hepatitis B virus, suppress hepatitis B surface antigen and stimulate the immune system."

Trial and Regulatory Overview

The NDA is supported by results from a pair of global phase 3 trials: B-Well 1 and B-Well 2. Both were multicenter, randomized, double-blind, placebo-controlled trials conducted across 29 countries. Enrolled participants were adults with CHB who were receiving nucleos(t)ide analogue (NA) therapy and had baseline hepatitis B surface antigen (HBsAg) levels of ≤3000 IU/mL.

The primary endpoint was the proportion of participants achieving functional cure, defined as undetectable HBsAg in blood for at least 24 weeks after cessation of all treatment, in the population with baseline HBsAg ≤3000 IU/mL. A key secondary endpoint assessed functional cure in patients with baseline HBsAg ≤1000 IU/mL.

According to the press release, bepirovirsen plus standard of care demonstrated statistically significant and clinically meaningful functional cure rates across all ranked endpoints compared to standard of care alone, with a more pronounced effect observed in patients with lower baseline HBsAg levels. The safety and tolerability profile was described as acceptable and consistent with prior studies.

Full data are expected to be presented at the European Association for the Study of the Liver (EASL) 2026 Congress in May 2026, with simultaneous peer-reviewed publication anticipated.

Bepirovirsen previously received Fast Track designation from the FDA in February 2024.2

Clinical Context

CHB is a major global public health burden, affecting an estimated 254 million people worldwide and causing approximately 1.1 million deaths annually, primarily from cirrhosis and hepatocellular carcinoma.² Current standard-of-care therapy with NAs effectively suppresses viral replication but rarely eliminates infection; functional cure rates with existing regimens are estimated at approximately 1% per year.4

Because functional cure is associated with meaningful reduction in long-term hepatic complications, including liver cancer, it is considered the paramount therapeutic goal in CHB management, but current treatments rarely achieve it.

Mechanism of Action and Drug Background

Bepirovirsen is an ASO designed to target and degrade HBV-derived RNA transcripts, thereby reducing production of viral proteins including HBsAg and hepatitis B e antigen. By suppressing HBsAg, the drug may relieve HBsAg-mediated immune tolerance, potentially enabling durable immune-mediated control of infection. This multi-pronged mechanism with direct viral RNA degradation and immunostimulatory effects distinguishes bepirovirsen from NA therapies, which suppress HBV DNA replication without meaningfully lowering HBsAg.

GSK licensed bepirovirsen from Ionis in 2019. The drug is currently under parallel regulatory review by the European Medicines Agency, China's National Medical Products Administration, and Japan's Ministry of Health, Labour and Welfare. It has received Breakthrough Therapy designation in China and SENKU designation in Japan.

References

1. BusinessWire/Ionis Pharmaceuticals. Ionis partner GSK announces bepirovirsen accepted for Priority Review and granted Breakthrough Therapy Designation by U.S. FDA as a potential first-in-class medicine for chronic hepatitis B. Published April 28, 2026. https://www.businesswire.com/news/home/20260427721143/en/Ionis-partner-GSK-announces-bepirovirsen-accepted-for-Priority-Review-and-granted-Breakthrough-Therapy-Designation-by-U.S.-FDA-as-a-potential-first-in-class-medicine-for-chronic-hepatitis-B

2. Brooks A. FDA Grants Fast Track Designation for Bepirovirsen for Chronic Hepatitis B. HCPLive. February 13, 2024. Accessed April 28, 2026. https://www.hcplive.com/view/fda-grants-fast-track-designation-for-bepirovirsen-for-chronic-hepatitis-b

3. Razavi-Shearer D, Gamkrelidze I, Nguyen MH, et al. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018;3(6):383-403.

4. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-1599.