FDA Grants First US Approval for Hepatitis Delta Treatment as Gilead's Hepcludex Ends Decades Without an Option
The FDA granted accelerated approval to Hepcludex (bulevirtide-gmod) on May 22, 2026, making it the first treatment cleared for chronic hepatitis delta virus infection in the United States.
Overview
The U.S. Food and Drug Administration granted accelerated approval to Hepcludex® (bulevirtide-gmod) on May 22, 2026, marking the first time any treatment has received regulatory clearance in the United States for chronic hepatitis delta virus (HDV) infection, according to Gilead Sciences via BusinessWire. The drug, developed by Gilead Sciences, is a first-in-class entry inhibitor administered as an 8.5 mg once-daily subcutaneous injection.
What We Know
HDV is a satellite virus that can only infect individuals who already carry chronic hepatitis B virus (HBV), affecting an estimated 40,000 to 80,000 people in the United States — representing 2% to 4% of individuals with chronic hepatitis B, as reported by Gilead Sciences via BusinessWire. Globally, at least 12 million people are co-infected with HDV and HBV. The disease carries mortality rates as high as 50% within five years in patients with cirrhosis, placing it among the most aggressive forms of viral hepatitis.
Hepcludex works by blocking the entry of both HDV and HBV into liver cells, addressing a key step in the viral lifecycle, as described by Gilead Sciences via BusinessWire. The European Medicines Agency describes the mechanism more specifically as bulevirtide “attaching to and blocking a receptor through which the hepatitis delta and hepatitis B viruses enter liver cells.”
The FDA’s accelerated approval was based on results from the pivotal, controlled Phase 3 MYR301 study (NCT03852719). At Week 48, the study demonstrated a statistically significant improvement versus the control (delayed treatment) group in a combined virologic and biochemical response, with treatment showing sustained efficacy and tolerability through up to 144 weeks of on-treatment exposure, according to Gilead Sciences via BusinessWire. The European Medicines Agency’s regulatory assessment of the same confirmatory trial reports that 48% (24 out of 50) of patients receiving the higher dose had almost all of their HDV RNA cleared at 48 weeks, compared with 2% (1 out of 51) of untreated patients.
The approval covers adults without cirrhosis or with compensated cirrhosis. The FDA granted the therapy Breakthrough Therapy Designation, Orphan-Drug Designation, and Priority Review before granting accelerated approval, according to Gilead Sciences via BioSpace. Accelerated approval is contingent on verification of clinical benefit through a confirmatory long-term outcomes trial.
“The approval of Hepcludex represents a historic milestone for people living with HDV in the United States, marking the first FDA-approved treatment for HDV,” said Dr. Dietmar Berger, Chief Medical Officer at Gilead Sciences, as quoted by Gilead Sciences via BusinessWire.
The most common adverse reactions, occurring in 10% or more of trial participants, were injection site reactions, headache, abdominal pain, fatigue, and pruritus. A boxed warning cautions that severe acute exacerbations of hepatitis D and hepatitis B may occur after Hepcludex is discontinued, particularly in patients with cirrhosis, according to Gilead Sciences via BioSpace. Hypersensitivity reactions including anaphylaxis have also been reported.
The drug is not entirely without regulatory precedent globally. The European Medicines Agency granted Hepcludex a conditional marketing authorisation throughout the EU on July 31, 2020, which was converted to a standard marketing authorisation on July 18, 2023 — meaning European patients have had access to the treatment for nearly six years ahead of its US approval.
What We Don’t Know
The FDA granted accelerated approval based on surrogate endpoints — reductions in HDV RNA and normalization of alanine aminotransferase (ALT) — rather than on demonstrated improvements in disease-related clinical outcomes such as reduction in cirrhosis or mortality. Whether those outcomes will improve with sustained treatment remains to be confirmed through the required post-approval trial.
The availability and pricing of Hepcludex in the United States has not been publicly disclosed. Gilead indicated that its Support Path® Program will offer resources helping patients understand coverage and financial assistance options.
Because HDV can only occur in individuals already infected with HBV, the long-term clinical benefit of the drug will also depend on whether co-infected patients are simultaneously managing their HBV, adding complexity to real-world treatment planning.
Analysis
The approval resolves a longstanding gap in hepatitis care that has persisted despite the disease’s severity. Hepatitis delta is classified as a rare disease in the United States, but its outcomes are disproportionately harsh: a 50% mortality rate within five years for patients with cirrhosis places it far above most common hepatitis presentations. The approximately six-year gap between European conditional approval and US clearance — the European Medicines Agency first authorized the drug in July 2020, according to its regulatory assessment — illustrates the different timelines at which the two regulatory systems evaluated the same clinical evidence.
The entry-inhibitor mechanism is also notable as a departure from the antiviral approaches used in HBV treatment. Rather than targeting viral replication after entry, bulevirtide prevents both viruses from reaching their intracellular target, which may offer advantages in co-infected patients by addressing both pathogens through a single mechanism.