FDA Approves First Treatment for Chronic Hepatitis Delta Virus Infection

The US Food and Drug Administration has approved bulevirtide-gmod (Hepcludex; Gilead Sciences) injection for the treatment of chronic hepatitis delta virus (HDV) infection in adults without cirrhosis or with compensated cirrhosis, marking the first FDA-approved therapy for chronic HDV infection.¹

HDV infection occurs only in individuals with hepatitis B virus (HBV) infection and can cause rapid progression to liver fibrosis, hepatocellular carcinoma, liver failure, and death, according to the FDA. Risk factors include unprotected sex, injection drug use, and occupational exposure to blood. HBV vaccination protects against both HBV and HDV infection.¹

“Today’s approval fills a critical gap in care for patients with chronic HDV infection, who until now have had no FDA-approved therapies available,” Wendy Carter, DO, acting director of the Office of Infectious Diseases in FDA’s Center for Drug Evaluation and Research, said in the announcement.¹

The approval was supported by data from MYR301, a multicenter, randomized, open-label, parallel-arm phase 3 trial. Participants were randomly assigned to immediate treatment with bulevirtide 8.5 mg once daily for 144 weeks or delayed treatment consisting of a 48-week observational period followed by bulevirtide 8.5 mg once daily for 96 weeks.²

The primary efficacy end point was combined response at week 48, defined as undetectable HDV RNA, or HDV RNA less than the lower limit of quantification of 50 IU/mL with target not detected, or at least a 2 log10 IU/mL decline from baseline, plus alanine aminotransferase normalization.²

At week 48, combined response was achieved by 48% of participants in the bulevirtide group compared with 2% in the delayed treatment group. The rate of undetectable HDV RNA at week 48 was 20% with bulevirtide vs 0% with delayed treatment. Among those receiving bulevirtide, the rate of undetectable HDV RNA increased to 36% at week 96 and 50% at week 144.²

Potential adverse effects include hypersensitivity reactions, including anaphylaxis, injection site reactions, headache, abdominal pain, fatigue, and pruritus. The prescribing information includes a boxed warning that discontinuation of bulevirtide may result in severe acute exacerbations of HDV and HBV infection.¹

The FDA granted bulevirtide Breakthrough Therapy Designation and Orphan Drug Designation. The therapy received priority review and was approved under the Accelerated Approval pathway.¹

References:

1. US Food and Drug Administration. FDA Approves First Treatment for Chronic Hepatitis Delta Virus (HDV) Infection. News release. May 22, 2026. Accessed May 22, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-chronic-hepatitis-delta-virus-hdv-infection
2. Gilead Sciences Inc. Final Data From the Phase 3 MYR301 Study Demonstrated Longer Treatment With Bulevirtide Was Associated With Sustaining Undetectability After Stopping Treatment. News. release. May 7, 2025. Accessed May 22, 2026. https://www.gilead.com/news/news-details/2025/final-data-from-the-phase-3-myr301-study-demonstrated-longer-treatment-with-bulevirtide-was-associated-with-sustaining-undetectability-after-stopping-treatment