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The FDA approved bulevirtide (Hepcludex; Gilead Sciences), the first treatment for hepatitis delta virus (HDV) infection in the US.
The 8.5-mg daily injection will treat adults with chronic HDV infection without cirrhosis or with compensated cirrhosis.
The approval “fills a critical gap in care for patients with chronic HDV infection, who until now have had no FDA-approved therapies available,” said Wendy Carter, DO, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research. The new treatment option “offers hope in managing a disease that can rapidly progress to serious liver complications.”
Efficacy, Side Effects
The approval follows positive findings in MYR301, a multicenter, randomized, open-label, parallel-arm phase 3 trial of bulevirtide with data at 48 weeks and 96 weeks.
Participants were randomly assigned to immediate treatment with bulevirtide 8.5 mg once daily for 144 weeks or to delayed treatment with an observational period of 48 weeks followed by bulevirtide 8.5 mg once daily for 96 weeks.
The main efficacy endpoint was combined response at week 48. This was defined as undetectable HDV RNA (less than the lower limit of quantification [50 IU/mL] with the target not detected) or a ≥ 2 log10 IU/mL decline from baseline and aminotransferase normalization.
At 48 weeks, the combined response was 48% vs 2% in the Hepcludex group vs the delayed treatment group, and the rate of undetectable HDV RNA was 20% vs 0% in the Hepcludex group vs 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.
Possible side effects associated with the drug include hypersensitivity reactions — anaphylaxis, injection site reactions, headache, abdominal pain, and fatigue.
The drug’s labeling includes a boxed warning that discontinuation may result in severe acute exacerbations of HDV and hepatitis B virus infection.
Priority Review
The FDA granted Hepcludex both breakthrough therapy and orphan drug designations. It received priority review and was approved under the agency’s accelerated approval pathway. Improvement in disease-related clinical outcomes has not been established, and continued approval for the approved indication may be contingent on verification and description of clinical benefit in a confirmatory trial.
Bulevirtide 2 mg is approved for use in the European Economic Area and other countries globally to treat people living with chronic HDV. However, the FDA rejected the drug at that dose in 2022.
“Since then, we continued to study the potential of bulevirtide at different doses and in combination with other therapies to improve outcomes for people living with chronic HDV,” a Gilead spokesperson told Medscape Medical News.
“Based on the totality of the currently available data from our clinical studies, the US FDA recognizes the potential value and benefits that the investigational 10-mg dose may offer to people living with HDV who currently have no approved treatment option in the US,” she said.
“Therefore,” she added, “Gilead has filed a biologics license application with these additional data and continues to work closely with the FDA to bring bulevirtide to people living with HDV in the US who could benefit from treatment.”
Bulevirtide is available now, according to a Gilead spokesperson.
Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.
