FDA approves first treatment for chronic hepatitis D virus

The FDA has granted accelerated approval for Gilead Sciences’ Hepcludex (bulevirtide-gmod) to treat adults living with chronic hepatitis delta virus (HDV) infection, a serious liver disease that occurs only as a co-infection in people with chronic hepatitis B virus.

Chronic hepatitis D is a severe form of viral hepatitis and is associated with a higher risk of rapid disease progression, liver failure, and mortality compared with hepatitis B alone. In the United States, studies in general populations have estimated that hepatitis D affects between 2% and 4% of people who have chronic hepatitis B.

“For patients, an HDV diagnosis means managing two distinct viral liver diseases — hepatitis B and hepatitis D — each contributing to disease progression, monitoring demands, and treatment complexities,” Ira Jacobson, M.D., director of hepatology in the Department of Medicine at NYU Grossman School of Medicine, said in a news release.

Hepcludex 8.5 mg is a first-in-class antiviral treatment for adults living with chronic hepatitis D infection. It is supplied as a vial for once-daily subcutaneous injection.

The accelerated approval was based on results from the pivotal phase 3 MYR301 study based on a decrease in HDV RNA and alanine aminotransferase (ALT) normalization. The trial included up to 144 weeks of treatment followed by 96 weeks of off-treatment follow-up.

At week 48, the study showed that Hepcludex demonstrated a statistically significant improvement in virologic and biochemical response compared with the control group, which consisted of patients who had received delayed treatment with Hepcludex. The rate of undetectable HDV RNA was 20% in the Hepcludex group compared with 0% in the delayed treatment group. At weeks 96 and 144, the rate of undetectable HDV RNA increased to 36% and 50%, respectively, in the Hepcludex group.

Hepcludex was generally well tolerated through up to 144 weeks of on-treatment exposure. Possible side effects include hypersensitivity reactions, including anaphylaxis (severe allergic reactions); injection site reactions; headache; abdominal pain; fatigue; and pruritus (itching). The labeling includes a boxed warning that discontinuation of Hepcludex may result in severe acute exacerbations of HDV and HBV infection.

In May 2025, Gilead announced final results from the MYR301 study, showing that 36% (23 out of 64) of adults living with chronic hepatitis D virus treated with bulevirtide at either a 2 mg or 10 mg dose maintained virologic suppression for almost two years after stopping treatment after achieving undetectable hepatitis RNA at the end of treatment.

In participants who sustained undetectability for one year after the end of therapy, no relapses occurred in the second year of follow-up. In addition, sustained post-treatment undetectable HDV RNA was more frequent in participants with longer on-treatment HDV RNA undetectability at the end of treatment: 90% (9/10) of those who had HDV RNA undetectability for ≥ 96 weeks at the end of treatment remained HDV undetectable off-treatment. These data were presented at the European Association for the Study of the Liver (EASL) Congress 2025.

Gilead had initially submitted a biologic license application for bulevirtide to the FDA in November 2021 based on interim data from the MYR301. But the FDA issued a complete response letter in October 2022, citing concerns regarding the manufacture and delivery of bulevirtide.