Bulevirtide + Peginterferon Alfa-2a: Optimal Chronic Hepatitis D Therapy

A recent study has highlighted the effectiveness of combining bulevirtide with peginterferon alfa-2a over using bulevirtide alone for treating chronic hepatitis D. Published on June 6 in the New England Journal of Medicine, the findings were presented at the European Association for the Study of the Liver's annual congress in Milan from June 5 to 8.

Conducted by Dr. Tarik Asselah and his team at Université de Paris-Cité, the phase 2b trial included patients with chronic hepatitis D. Participants were divided into three groups with different treatment regimens: peginterferon alfa-2a alone (180 μg per week) for 48 weeks (24 patients); bulevirtide (either 2 mg or 10 mg daily) combined with peginterferon alfa-2a (180 μg per week) for 48 weeks followed by bulevirtide alone for another 48 weeks (50 patients at each dose level); and bulevirtide alone (10 mg daily) for 96 weeks (50 patients).

Results showed notable differences in the effectiveness of these treatments. At 24 weeks post-treatment, 17% of the patients in the peginterferon alfa-2a group had undetectable levels of HDV RNA. This was observed in 32% of patients receiving the 2-mg bulevirtide plus peginterferon alfa-2a combination, and in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group. In contrast, only 12% of patients treated with 10-mg bulevirtide monotherapy achieved undetectable HDV RNA levels. Specifically, the 10-mg bulevirtide plus peginterferon alfa-2a group showed a 34 percentage point higher success rate in achieving undetectable HDV RNA levels compared to the monotherapy group.

At 48 weeks post-treatment, the corresponding percentages of patients with undetectable HDV RNA levels were 25% for the peginterferon alfa-2a group, 26% for the 2-mg bulevirtide plus peginterferon alfa-2a group, 46% for the 10-mg bulevirtide plus peginterferon alfa-2a group, and 12% for the 10-mg bulevirtide monotherapy group. 

The study also reported that the majority of adverse events were mild to moderate, with the most common being leukopenia, neutropenia, and thrombocytopenia.

The researchers concluded that a finite-duration regimen combining bulevirtide with peginterferon alfa-2a led to a sustained undetectable HDV RNA response that persisted beyond 24 weeks after treatment had ended. This suggests a promising approach for managing chronic hepatitis D with a combination therapy that proves more effective than monotherapy.

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