FDA grants accelerated approval to Gilead’s Hepcludex for chronic hepatitis delta virus infection

Edited by Robert McTiernan··2 min read

Gilead Sciences (Nasdaq: GILD) has received US FDA accelerated approval for Hepcludex (bulevirtide-gmod) for the treatment of chronic hepatitis delta virus (HDV) infection in adults without cirrhosis or with compensated cirrhosis, making it the first therapy to receive FDA approval for this indication.

Hepcludex is administered as an 8.5 mg once-daily subcutaneous injection. The accelerated approval was granted on the basis of reductions in HDV RNA and normalization of alanine aminotransferase (ALT) as surrogate endpoints. The FDA has not yet established whether the drug improves disease-related clinical outcomes, and continued approval may be contingent on verification of clinical benefit in a confirmatory trial, which Gilead said has already been initiated. The label carries a boxed warning regarding severe acute exacerbations of hepatitis D and B following treatment discontinuation, with a requirement for hepatic function monitoring for at least six months after stopping therapy.

The approval was supported primarily by data from MYR301 (NCT03852719), a Phase III controlled study evaluating Hepcludex in adults with chronic HDV. The trial’s primary endpoint assessed combined virologic and biochemical response at Week 48, comparing Hepcludex against a delayed-treatment control group. The study met this endpoint with a statistically significant improvement over control, and continued treatment showed sustained efficacy through up to 144 weeks of on-treatment exposure. The drug was described as generally well tolerated across this period.

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Mechanism and context

Bulevirtide is a synthetic lipopeptide that mimics the preS1 domain of the HBV large surface protein, competitively blocking the NTCP (sodium taurocholate co-transporting polypeptide) receptor on hepatocytes and preventing both HBV and HDV from entering liver cells. Because HDV can only replicate in the presence of HBV co-infection, targeting the shared entry mechanism addresses a fundamental step in the lifecycle of both viruses simultaneously.

Prior to this approval, no FDA-sanctioned therapy existed for chronic HDV; peginterferon alfa-2a has served as the de facto standard of care in clinical practice, used off-label in the US despite its limited tolerability and high relapse rates. Vir Biotechnology’s combination of tobevibart and elebsiran is currently in Phase III development under the ECLIPSE program, with trials designed to include Hepcludex as an active comparator arm, representing the most direct late-stage competitive challenge to Gilead’s position in this indication.

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