FDA Approves First Drug for Chronic Hepatitis Delta Virus

The FDA approved bulevirtide-gmod (Hepcludex) for the treatment of chronic hepatitis delta virus (HDV) infections in adults. This decision marks the first and only FDA-approved therapy for a condition that has historically been considered the most severe and rapidly progressing form of viral hepatitis.^1,2

"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.¹ "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."

Indicated for patients without cirrhosis or those with compensated cirrhosis, bulevirtide-gmod addresses a critical gap in care for an estimated 40,000 to 80,000 Americans living with this disease. Pharmacists should recognize this medication as a first-in-class entry inhibitor that functions by blocking the entry of both HDV and the hepatitis B virus (HBV) into hepatocytes. Because HDV is a satellite virus that can only replicate in the presence of HBV, this mechanism targets a vital step in the viral lifecycle by preventing the virus from utilizing HBV envelope proteins for assembly and infection.^2,3

The FDA granted this approval under the accelerated approval pathway, a status reserved for innovative therapies treating serious conditions with unmet medical needs, supported by promising data from the phase 3 MYR301 (NCT03852719) trial. In this multicenter, randomized study, patients receiving an 8.5 mg daily subcutaneous injection of bulevirtide-gmod demonstrated a 48% combined response rate at week 48, which was defined by undetectable HDV RNA or a significant viral load decline alongside the normalization of alanine aminotransferase levels.^1,2

In contrast, the delayed treatment group showed only a 2% response rate during the same period. Long-term data from the trial further highlighted the drug's efficacy, with the rate of undetectable HDV RNA increasing to 50% by week 144. Although these biochemical and virologic improvements are significant, pharmacists should note that clinical benefits regarding long-term disease-related outcomes have not yet been fully established, and continued approval may depend on verification in confirmatory trials.

For pharmacy, understanding the clinical nuances of HDV is essential, as it often presents as coinfection, where a patient acquires HBV and HDV simultaneously, and superinfection, where HDV is acquired by someone already living with chronic HBV. Superinfection is particularly dangerous, as up to 90% of these individuals develop chronic infections that can lead to rapid liver fibrosis, liver failure, and a mortality rate that is significantly higher than HBV infection alone.^3,4

Despite its severity, HDV remains uncommon in the United States and is often underdiagnosed, making it imperative for those with chronic HBV to undergo a simple blood test for HDV. Although HBV vaccination remains the most effective prevention against both viruses, bulevirtide-gmod now offers a viable management strategy for those already infected.

“Hepatitis delta virus is associated with rapid progression of liver disease and a high risk of serious or even life-threatening liver-related complications,” Ira Jacobson, MD, in the department of medicine at NYU Grossman School of Medicine, said in a news release.² “For patients, an HDV diagnosis means managing 2 distinct viral liver diseases—hepatitis B and hepatitis D—each contributing to disease progression, monitoring demands, and treatment complexities.”

Safety and monitoring are paramount when dispensing this new injectable therapy. Bulevirtide-gmod carries a boxed warning regarding the risk of severe acute exacerbations of both HDV and HBV following the discontinuation of treatment. Pharmacists must counsel patients on the importance of adherence and ensure that hepatic function is monitored closely for at least 6 months if the medication is stopped, particularly in patients with cirrhosis who are at a higher risk for hepatic decompensation.²

Common adverse reactions reported in clinical trials include injection site reactions, headache, abdominal pain, fatigue, and pruritus, while more serious hypersensitivity reactions like anaphylaxis have also been observed. As the primary point of contact for medication management, pharmacists will play a vital role in integrating this historic treatment into the clinical pathway for patients facing the complexities of chronic HDV.^1,2

Are you ready to elevate your pharmacy practice? Sign up today for our free Drug Topics newsletter and get the latest drug information, industry trends, and patient care tips straight to your inbox.

REFERENCES

1. FDA approves first treatment for chronic hepatitis delta virus (HDV) infection. News release. FDA. May 22, 2026. Accessed May 26, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-chronic-hepatitis-delta-virus-hdv-infection

2. FDA grants accelerated approval to Gilead’s Hepcludex (bulevirtide-gmod), the first and only approved treatment for chronic hepatitis delta virus (HDV). News release. Gilead. May 22, 2026. Accessed May 26, 2026. https://www.gilead.com/news/news-details/2026/fda-grants-accelerated-approval-to-gileads-hepcludex-bulevirtide-gmod-the-first-and-only-approved-treatment-for-chronic-hepatitis-delta-virus-hdv

3. Hepatitis B Foundation. What is hepatitis delta? https://www.hepb.org/research-and-programs/hepdeltaconnect/what-is-hepatitis-delta/

4. CDC. Hepatitis D basics. April 24, 2024. Accessed May 26, 2026. https://www.cdc.gov/hepatitis-d/about/index.html