On May 22, 2026, the U.S. Food and Drug Administration (FDA) approved Hepcludex (bulevirtide-gmod) as the first medication for the treatment of chronic hepatitis D virus (HDV) infection in adult patients with compensated liver disease.
The drug was approved under the accelerated approval pathway, a mechanism used for the authorization of therapies for serious diseases where alternative treatment options are limited or nonexistent. The registration holder for the product is the American biopharmaceutical company Gilead Sciences, Inc.
Overview of Hepatitis D
Hepatitis D (delta hepatitis) is an inflammatory liver disease caused by the hepatitis D virus (HDV). Because HDV requires the hepatitis B virus (HBV) for replication, delta hepatitis infection cannot occur in the absence of HBV. HDV-HBV coinfection is considered the most severe form of chronic viral hepatitis, as it is associated with a more rapid progression to hepatocellular carcinoma and liver-related mortality. Vaccination against hepatitis B effectively provides protection against HDV infection. Furthermore, according to the International Agency for Research on Cancer (IARC) classification, HDV has recently been classified as a carcinogenic agent for humans (Group 1), similar to hepatitis B and C viruses.
According to World Health Organization (WHO) estimates, HDV is found in approximately 5% of people worldwide with chronic HBV infection, and HDV coinfection is a possible cause of one in five cases of liver disease and liver cancer among HBV-infected patients. Gilead Sciences estimates that approximately 40,000 to 80,000 patients live with this disease in the United States.
Treatment Landscape
Prior to the approval of Hepcludex, the only therapeutic option for delta hepatitis was pegylated interferon-alpha (PEG-IFNα). However, its clinical use was significantly limited by poor efficacy, adverse effects, and contraindications. Under PEG-IFNα therapy, a complete virological response is achieved in only 20–30% of patients, and post-treatment relapse is a frequent clinical occurrence.
Mechanism of Action
Bulevirtide is a synthetic lipopeptide derived from the preS1 domain of the HBV large surface protein. Its mechanism of action is based on the competitive inhibition of the sodium-taurocholate cotransporting polypeptide (NTCP) receptor, which blocks the de novo entry of both HBV and HDV into hepatocytes.
Clinical Efficacy
The drug’s efficacy was demonstrated in the MYR301 Phase III, multicenter, randomized, open-label trial. Participants were randomized into an immediate-treatment group and a delayed-treatment group. The immediate-treatment group received 8.5 mg of bulevirtide for 144 weeks, while the delayed-treatment group underwent an initial 48-week observation period followed by 96 weeks of therapy.
At week 48, a combined virological and biochemical response—defined as undetectable HDV RNA or a reduction of and normalization of alanine aminotransferase (ALT) activity—was observed in 48% of the immediate-treatment group, compared to only 2% in the delayed-treatment group. Additionally, the rate of undetectable HDV RNA increased from 20% at week 48 to 50% by week 144, indicating a progressive deepening of the virological response under prolonged therapy.
Safety and Regulatory Notes
The product labeling includes a warning that discontinuation of bulevirtide may lead to the exacerbation of HDV and HBV infections. Common adverse reactions include anaphylaxis, injection site reactions, headache, abdominal pain, fatigue, and pruritus.
Due to its “accelerated approval” status, final authorization of the product is contingent upon confirmation of clinical benefit in confirmatory clinical trials. It is also notable that the European Medicines Agency (EMA) granted the drug conditional marketing authorization in 2020.
Sources: fda.gov
