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Promising Combination Therapy for Chronic Hepatitis D: Bulevirtide and Pegylated Interferon Alpha

Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
Posted on August 16th, 2024
Recently, many European countries have approved bulevirtide for the treatment of chronic Hepatitis D infection. This medication exerts its antiviral effects by inhibiting the entry of the virus into hepatocytes through the sodium/bile acid cotransporter. Prior to the approval of bulevirtide, pegylated interferon alpha was commonly used off-label for this condition. Consequently, a study sponsored by Gilead Sciences was conducted to evaluate the combined effect of bulevirtide and pegylated interferon alpha.

The phase 2 clinical trial included a total of 175 patients who had chronic hepatitis D infection with HDV RNA detected via polymerase chain reaction. More than 30% of the participants had developed liver cirrhosis and the average level of alanine aminotransferase (ALT) is around 110 U/liter. The participants were randomly assigned into one of 4 treatment groups:
  1. Interferon monotherapy: subcutaneous peginterferon alfa-2a at a dose of 180 μg per week for 48 weeks
  2. Low-dose bulevirtide combination therapy: subcutaneous bulevirtide at a dose of 2 mg per day for 96 weeks with 180 μg of subcutaneous peginterferon alfa-2a per week for the first 48 weeks
  3. High-dose bulevirtide combination therapy: subcutaneous bulevirtide at a dose of 10 mg per day for 96 weeks with 180 μg of subcutaneous peginterferon alfa-2a per week for the first 48 weeks
  4. High-dose bulevirtide monotherapy: subcutaneous bulevirtide at a dose of 10 mg day for 96 weeks
At the 24th week post-treatment evaluation, the group receiving the high-dose combination of 10 mg bulevirtide plus peginterferon alfa-2a showed the most effective viral suppression, with 46% of participants having no detectable HDV RNA. This was significantly higher than the 12% suppression rate in the bulevirtide monotherapy group and 17% in the interferon monotherapy group. Additionally, a greater proportion of those treated with the high-dose combination achieved ALT normalization. These promising results led researchers to conclude that the combination of bulevirtide and pegylated interferon alpha is a viable therapeutic option for chronic Hepatitis D infection, warranting further investigation in a larger phase 3 study.