The US Food and Drug Administration has approved bulevirtide-gmod injection for adults with chronic hepatitis delta virus infection who do not have cirrhosis or who have compensated cirrhosis, marking the first FDA-approved therapy for the disease. The drug, marketed by Gilead Sciences, Inc. as Hepcludex, received accelerated approval based on phase 3 trial data showing higher rates of virologic and biochemical response compared with delayed treatment.
Hepatitis delta virus (HDV) infection occurs only in patients with hepatitis B virus infection and is associated with rapid progression to liver fibrosis, hepatocellular carcinoma, liver failure, and death. Risk factors include unprotected sex, injection drug use, and occupational blood exposure. Vaccination against hepatitis B virus also protects against HDV infection.
The approval, announced on May 22, was supported by findings from MYR301, a multicenter, randomized, open-label, parallel-arm phase 3 trial. Investigators assigned patients either to immediate treatment with bulevirtide 8.5 mg once daily for 144 weeks or to delayed treatment consisting of a 48-week observational period followed by 96 weeks of therapy.
The primary endpoint was a combined response at week 48, defined as undetectable HDV RNA or at least a 2 log10 IU/mL decline from baseline plus normalization of alanine aminotransferase (ALT) levels. At week 48, 48% of patients receiving immediate bulevirtide achieved the combined response compared with 2% in the delayed-treatment group.
Rates of undetectable HDV RNA also favored active treatment. At week 48, 20% of patients in the bulevirtide group had undetectable viral levels compared with none in the delayed-treatment group. The proportion of patients with undetectable HDV RNA increased over time, reaching 36% at week 96 and 50% at week 144 among patients treated with bulevirtide.
The FDA did not provide subgroup analyses in the approval announcement. The study’s open-label design and delayed-treatment comparator may limit interpretation of long-term comparative efficacy, although the findings demonstrated sustained antiviral activity over nearly 3 years of therapy.
The prescribing information includes a boxed warning that discontinuation of bulevirtide may lead to severe acute exacerbations of HDV and hepatitis B virus infection. Reported adverse effects included hypersensitivity reactions, including anaphylaxis, injection-site reactions, headache, abdominal pain, fatigue, and pruritus.
The FDA granted bulevirtide Breakthrough Therapy and Orphan Drug designations and reviewed the application under the agency’s Priority Review and Accelerated Approval pathway.
In a statement accompanying the approval, Wendy Carter, DO, acting director of the Office of Infectious Diseases in the FDA's Center for Drug Evaluation and Research, said, “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.”
Prescribing information can be found here.