FDA grants accelerated approval to Gilead’s Hepcludex® (bulevirtide‑gmod) 8.5 mg, the first U.S. therapy for chronic hepatitis delta virus (HDV). Approval is based on surrogate endpoints, with confirmatory outcomes studies underway.
Written By: Sana Khan, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration has granted accelerated approval to Gilead Sciences’ Hepcludex® (bulevirtide-gmod) 8.5 mg, marking the first and only FDA-approved treatment for adults with chronic hepatitis delta virus (HDV) infection. The indication covers patients without cirrhosis or with compensated cirrhosis.
Approval was based on reductions in HDV RNA and normalization of alanine aminotransferase (ALT), surrogate markers of antiviral activity and liver inflammation. Clinical benefit on long-term liver outcomes has not yet been established. Continued approval will depend on confirmatory outcomes data from an ongoing long-term study.
Disease Burden and Unmet Need
HDV is considered the most aggressive form of viral hepatitis and occurs only in individuals already infected with hepatitis B virus (HBV). U.S. estimates suggest 40,000–80,000 people may be living with HDV. Compared with HBV monoinfection, HDV co-infection significantly increases the risk of fibrosis, hepatic decompensation, hepatocellular carcinoma, and mortality. Chronic HDV can lead to mortality rates approaching 50% within five years in cirrhotic patients.
Mechanism of Action
Hepcludex is a first-in-class viral entry inhibitor that targets the sodium taurocholate co-transporting polypeptide (NTCP) receptor, preventing HDV and HBV entry into hepatocytes. The therapy is administered as a once-daily subcutaneous injection.
Clinical Evidence
The FDA decision was supported by the Phase 3 MYR301 study (NCT03852719), which evaluated Hepcludex in adults with chronic HDV infection for up to 144 weeks, followed by 96 weeks of off-treatment follow-up. At Week 48, the trial met its primary endpoint, demonstrating statistically significant improvement in combined virologic and biochemical responses, including reductions in HDV RNA and ALT normalization, compared with a delayed-treatment control group.
Long-term treatment maintained durable antiviral activity, and the therapy was generally well tolerated through nearly three years of exposure.
Expert and Company Commentary
Dr. Ira Jacobson of NYU Grossman School of Medicine noted that the approval addresses a long-standing treatment gap for patients managing both hepatitis B and hepatitis D, conditions that together accelerate liver disease progression and complicate clinical management.
Gilead Chief Medical Officer Dietmar Berger emphasized that the approval reflects years of regulatory collaboration and introduces the first approved therapeutic option for a patient population with longstanding unmet need.
Safety and Labeling
The prescribing information includes a boxed warning for severe post-treatment exacerbation of hepatitis B and hepatitis D after discontinuation, particularly in patients with cirrhosis who may face increased risk of hepatic decompensation.
The FDA recommends close monitoring of liver function, HBV DNA, and HDV RNA for at least six months after treatment cessation.
Global Context and Next Steps
The U.S. approval applies to the 8.5 mg formulation of bulevirtide. Bulevirtide 2 mg is already approved in the European Economic Area and several other global markets for chronic HDV infection.
Gilead has initiated a long-term confirmatory outcomes study required under the FDA’s accelerated approval pathway to establish clinical benefit beyond surrogate endpoints.
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