RCT | Bulevirtide reduces HDV RNA and ALT levels in chronic hepatitis D patients

Summary: This randomized phase 3 trial evaluated the efficacy of bulevirtide, an inhibitor of HDV entry into hepatocytes, in patients with chronic hepatitis D. Patients were randomized to receive either 2 mg or 10 mg of bulevirtide daily for 144 weeks, or no treatment for 48 weeks followed by 10 mg bulevirtide daily for 96 weeks. The study involved 150 patients, 49 in the 2-mg group, 50 in the 10-mg group, and 51 in the control group.

After 48 weeks of treatment, 45% and 48% of patients in the 2-mg and 10-mg groups respectively achieved the primary end point of undetectable HDV RNA level or a decrease of at least 2 log10 IU per milliliter from baseline, and normalization of ALT level. Only 2% in the control group reached the primary endpoint. ALT levels normalized in 51% and 56% of patients in the 2-mg and 10-mg groups respectively, a significant difference from the 12% normalization in the control group. Notably, loss of HBsAg did not occur by week 48 in the bulevirtide groups. No serious adverse events related to the treatment were reported, though side effects including headache, pruritus, and fatigue were more common in the bulevirtide groups.

These results demonstrate the effectiveness of bulevirtide in reducing HDV RNA and ALT levels in patients with chronic hepatitis D. However, the absence of HBsAg loss in bulevirtide groups raises questions about its long-term implications.

Article: A Phase 3, Randomized Trial of Bulevirtide in Chronic Hepatitis D – New England Journal of Medicine (link to abstract – $ for full-text)

Commentary on Twitter

Presented today at #EASLCongress: In a randomized trial, 48 weeks of treatment with bulevirtide, which inhibits hepatitis D virus entry into hepatocytes, reduced HDV RNA and alanine aminotransferase levels in patients with chronic hepatitis D. https://t.co/Q8RNZFbQlQ

— NEJM (@NEJM) June 22, 2023