Bepirovirsen for Chronic Hepatitis B Receives Breakthrough Therapy Designation, Priority Review

With the potential for bepirovirsen (Ionis Pharmaceuticals and GSK) to be a first-in-class functional cure for chronic hepatitis B (CHB), the FDA has accepted its new drug application for priority review and also granted it a breakthrough therapy designation.¹ The drug is an investigational antisense oligonucleotide and would be the first therapy to achieve clinically meaningful functional cure rates in adults with CHB if it is approved. The agency set a target action date of October 26, 2026.

Approximately 640,000 US adults have CHB, with non-Hispanic Asian/Pacific Islander people being disproportionately affected and having the highest rate of CHB.² The risk of developing CHB is related to the age of exposure. While only 5% to 10% of healthy adults infected with acute hepatitis B will develop CHB, up to 50% of infected young children will develop CHB, and more than 90% of infants infected develop CHB.³

“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, CEO of Ionis Pharmaceuticals, said in a statement.¹ “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.”

A Disease With Few Options and High Stakes

Despite the availability of nucleos(t)ide analogue (NA) therapies that effectively suppress viral replication, a functional cure—defined as sustained undetectable hepatitis B surface antigen (HBsAg) in blood following treatment cessation—is achieved in only approximately 1% of patients per year on existing regimens.¹

Patients with CHB on NA often require lifelong therapy, which can cause issues with ongoing adherence to therapy and maintaining regular follow-up testing.⁴

A functional cure is considered the paramount therapeutic goal in CHB because it is associated with meaningful reductions in long-term liver complications, including cancer.^2,5 The lack of a viable path to cure represents a significant gap in care.

Phase 3 Evidence Across 29 Countries

The application is supported by data from the B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820) phase 3, multicenter, randomized, double-blind, placebo-controlled studies conducted across 29 countries.^1,6 Participants were adults with CHB on NA therapy who had baseline HBsAg levels of 3000 IU/mL or less.

The primary end point was the proportion of participants achieving functional cure—defined as undetectable HBsAg for at least 24 weeks after stopping all treatment—in the population with baseline HBsAg of 3000 IU/mL or less. A key secondary end point evaluated functional cure in those with baseline HBsAg of 1000 IU/mL or less.

Bepirovirsen plus standard of care demonstrated statistically significant and clinically meaningful functional cure rates across all ranked end points compared with standard of care alone, with a more pronounced effect in patients with lower baseline HBsAg levels. The safety and tolerability profile was described as acceptable and consistent with prior studies.

Full trial data are expected to be presented at the European Association for the Study of the Liver 2026 Congress in May 2026.

How Bepirovirsen Works

As an antisense oligonucleotide, bepirovirsen targets and degrades hepatitis B virus–derived RNA transcripts, reducing production of viral proteins. By suppressing HBsAg, which is thought to mediate immune tolerance, the drug may enable durable, immune-mediated control of infection. This dual mechanism of direct viral RNA degradation and immunostimulation distinguishes bepirovirsen from NA therapies, which suppress hepatitis B virus DNA replication without meaningfully lowering HBsAg.

References

1. 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. News release. Ionis Pharmaceuticals. April 28, 2026. Accessed May 5, 2026. https://ir.ionis.com/news-releases/news-release-details/ionis-partner-gsk-announces-bepirovirsen-accepted-priority

2. Hepatitis B basics. CDC. August 29, 2025. Accessed May 5, 2026. https://www.cdc.gov/hepatitis-b/about/index.html

2. Acute vs. chronic hepatitis B. Hepatitis B Foundation. Accessed May 5, 2026. https://www.hepb.org/what-is-hepatitis-b/what-is-hepb/acute-vs-chronic/

4. Jackson M, Ibrahim Y, Freedland C, Jacob S, Zovich B, Cohen C. Barriers to accessing hepatitis B medication: a qualitative study from the USA and Canada. BMJ Open. 2024;14(5):e080658. doi:10.1136/bmjopen-2023-080658

5. Marrapu S, Soni JR, Kamal K, Kumar R. Hepatitis B functional cure: current and future perspective. World J Hepatol. 2025;17(10):110107. doi:10.4254/wjh.v17.i10.110107

6. Ionis partner GSK announces positive topline results from B-Well 1 and B-Well 2 Phase 3 studies for bepirovirsen, a potential first-in-class medicine for chronic hepatitis B. News release. Ionis Pharmaceuticals. January 7, 2026. Accessed May 5, 2026. https://ir.ionis.com/news-releases/news-release-details/ionis-partner-gsk-announces-positive-topline-results-b-well-1