Bulevirtide Receives Historic First FDA Approval for Chronic Hepatitis Delta

The US Food and Drug Administration (FDA) has approved bulevirtide (Hepcludex) injection for chronic hepatitis delta virus (HDV) infection in adults without cirrhosis or with compensated cirrhosis.¹ Bulevirtide is the first FDA-approved therapy for chronic HDV infection. The agency granted approval of the first-in-class entry inhibitor to Gilead Sciences on May 22, 2026, under the Accelerated Approval pathway.¹

Until this decision, no antiviral was approved in the US specifically for HDV, and clinicians relied on off-label, interferon-based regimens with limited efficacy.

"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," said Wendy Carter, DO, acting director of the Office of Infectious Diseases in FDA’s Center for Drug Evaluation and Research. "For individuals living with this chronic viral infection, this new treatment option offers hope in managing a disease that can rapidly progress to serious liver complications."

MYR301, Buleviritde, and Hepatitis D Efficacy

The approval was supported by MYR301, a multicenter, randomized, open-label, parallel-arm phase 3 trial. Participants were assigned to immediate treatment with bulevirtide 8.5 mg once daily for 144 weeks or to delayed treatment, consisting of a 48-week observational period followed by bulevirtide 8.5 mg once daily for 96 weeks.¹

The primary efficacy endpoint was combined response at week 48. Combined response was defined as undetectable HDV RNA, reported as below the lower limit of quantification (LLOQ) of 50 IU/mL with target not detected, or a decline of at least 2 log10 IU/mL from baseline, together with alanine aminotransferase (ALT) normalization.¹

At week 48, combined response was achieved in 48% of patients in the bulevirtide group compared with 2% in the delayed-treatment group.¹ The 46-percentage-point difference formed the basis for the accelerated approval, with combined response serving as the primary efficacy endpoint. In MYR301, virologic suppression continued to deepen through 144 weeks, supporting extended dosing in responding patients.¹

Bulevirtide safety profile and boxed warning

Among secondary measures, the rate of undetectable HDV RNA at week 48 was 20% in the bulevirtide group compared with 0% in the delayed-treatment group.¹ Virologic suppression deepened with continued dosing. The proportion of patients with undetectable HDV RNA rose to 36% at week 96 and to 50% at week 144, indicating progressive response across the 144-week treatment period.¹

The most common adverse reactions reported with the once-daily injection include headache, abdominal pain, fatigue, and pruritus, along with injection site reactions.¹ Hypersensitivity reactions, including anaphylaxis, have also been reported.

The label carries a boxed warning for severe acute exacerbations of hepatitis. Discontinuation of bulevirtide may result in severe acute exacerbations of HDV and HBV infection, according to the FDA.¹ The warning is clinically relevant given the agent's chronic, multiyear dosing schedule.

The FDA granted bulevirtide Breakthrough Therapy and Orphan Drug designations, and the application received priority review.¹ The agency described the decision as part of its effort to expedite access to therapies for diseases with limited or no treatment options.¹

Bulevirtide already holds full marketing authorization in the European Union, the United Kingdom, and Switzerland for chronic HDV.

References

1. US Food and Drug Administration. FDA approves first treatment for chronic hepatitis delta virus (HDV) infection. Published May 22, 2026. Accessed May 22, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-chronic-hepatitis-…

2. Wedemeyer H, Aleman S, Brunetto MR, et al. A phase 3, randomized trial of bulevirtide in chronic hepatitis D. N Engl J Med. 2023;389(1):22-32. doi:10.1056/NEJMoa2213429