FDA Approves Bulevirtide-gmod as First-Ever Treatment for Chronic Hepatitis Delta Virus Infection

The FDA 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 this serious and potentially fatal condition.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 the FDA’s Center for Drug Evaluation and Research, said in a news release from the FDA.¹

Understanding HDV

Hepatitis D is caused by the hepatitis D virus (HDV), a small RNA virus that depends on hepatitis B virus (HBV) for entry into hepatocytes to replicate. Among individuals with chronic HBV infection, an estimated 13% are coinfected with HDV, with approximately 48 million to 60 million infections diagnosed globally. Patients with HDV are more likely to develop cirrhosis than patients with HBV alone; on average, cirrhosis develops within 5 years of infection and hepatocellular carcinoma within 10 years. Because HDV can only infect individuals with HBV, HBV vaccination protects against both viruses. Prior to today's approval, only pegylated interferon-ɑ (PEG-INF-ɑ) was available for off-label treatment.^1,2

Mechanism of Action

Bulevirtide is a myristoylated peptide that mimics a region of the pre-S1 HBsAg recognized by the sodium taurocholate cotransporting polypeptide (NTCP) receptor, which HBV and HDV use to enter hepatocytes. By competitively inhibiting this entry, the drug decreases the number of HDV-infected hepatocytes.²

Phase 3 Trial: MYR301

Efficacy was demonstrated in the multi-center, randomized, open-label, parallel-arm phase 3 MYR301 trial (NCT03852719), in which participants were randomly assigned to immediate treatment with bulevirtide 8.5 mg once daily for 144 weeks or to a delayed-treatment arm with a 48-week observational period followed by bulevirtide 8.5 mg once daily for 96 weeks. The primary endpoint, a combined response of undetectable HDV RNA or 2 log10 IU/mL or greater decline from baseline plus ALT normalization at week 48, was achieved in 48% of the bulevirtide 10 mg group versus 2% in the delayed-treatment group. At week 48, undetectable HDV RNA was observed in 20% of the bulevirtide group versus 0% in the delayed-treatment group, a rate that climbed to 36% at week 96 and 50% at week 144.^1,3,4

Final data from MYR301, presented at the European Association for the Study of the Liver Congress 2025, further confirmed the durability of response. Ninety percent of patients with chronic HDV who achieved undetectable HDV RNA at 96 weeks of treatment remained undetectable for nearly 2 years post-treatment.⁵

Safety, Warnings, and Implications for Pharmacy Practice

Possible adverse effects include hypersensitivity reactions (including anaphylaxis), injection site reactions, headache, abdominal pain, fatigue, and pruritus. The labeling carries a boxed warning that discontinuation of bulevirtide may result in severe acute exacerbations of both HDV and HBV infection.¹

For pharmacists in specialty, infectious disease, and hepatology settings, the approval introduces an important new subcutaneous injectable to the formulary. Patients initiating bulevirtide should be counseled on proper injection technique, monitored for hypersensitivity reactions, and strongly advised against abrupt discontinuation given the boxed warning for severe viral exacerbation. Pharmacists can also play a meaningful role in HDV prevention by promoting HBV vaccination in at-risk populations, as the HBV vaccine remains the most effective protection against HDV infection.^1,2

REFERENCES

1. FDA approves first treatment for chronic hepatitis delta virus (HDV) infection. News release. FDA. Released 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. Seo H. Hepatitis D coinfection: what pharmacists need to know about emerging treatment options. Pharmacy Times. Published January 1, 2026. Accessed May 22, 2026. https://www.pharmacytimes.com/view/hepatitis-d-coinfection-what-pharmacists-need-to-know-about-emerging-treatment-options

3. 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

4. Study to assess efficacy and safety of bulevirtide in participants with chronic hepatitis delta (CHD) (MYR301). ClinicalTrials.gov Identifier: NCT03852719. Updated May 7, 2025. Accessed May 22, 2026. https://clinicaltrials.gov/study/NCT03852719

5. Final data from the phase 3 MYR301 study demonstrated longer treatment with bulevirtide was associated with sustaining undetectability after stopping treatment. News release. Gilead Sciences. Released 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