Bulevirtide monotherapy has been shown to be safe and well-tolerated in patients with chronic hepatitis delta (CHD) through 48 weeks of use, according to an integrated analysis of data from multiple clinical trials. The findings suggest a consistent and predictable safety profile for bulevirtide, particularly when compared to Pegylated interferon-alpha (Peg-IFNα).
The analysis, led by Tarik Asselah, MD, PhD, from the Université de Paris-Cité Hôpital Beaujon, combined data from three multi-center, open-label, randomized phase 2 and 3 clinical studies (MYR203, MYR204, and MYR301) conducted across seven countries. These studies evaluated bulevirtide at doses of 2 mg and 10 mg as monotherapy for 48 weeks, comparing it to Peg-IFNα and a delayed-treatment control group.
Trial Design and Patient Population
The trials enrolled men and women aged 18-65 years with CHD, detectable HDV RNA, and elevated ALT levels, with or without compensated cirrhosis. Participants were divided into four cohorts: bulevirtide 2 mg (n=64), bulevirtide 10 mg (n=115), Peg-IFNα (n=39), and a delayed-treatment control arm (n=51). The 10 mg dose of bulevirtide was administered as two 5 mg subcutaneous injections, while the 2 mg dose was given as a single injection.
Safety and Tolerability Findings
The integrated analysis revealed that bulevirtide monotherapy was safe and well-tolerated, with no serious adverse events (AEs) directly linked to the treatment. Common AEs included injection-site reactions (16% with bulevirtide 2 mg, 20% with bulevirtide 10 mg, and 0% in the control), increased total bile acid levels (20% with 2 mg, 17% with 10 mg, and 0% in the control), headache (16%, 17%, and 0%, respectively), itch (11%, 10%, and 0%, respectively), and eosinophilia (9%, 4%, and 0%, respectively).
While bulevirtide was associated with increased total bile acid levels, investigators found no clear correlation between these increases and other AEs such as eosinophilia, itch, or vitamin D deficiency. Grade 3 or 4 AEs connected to the study drug were more frequent in the Peg-IFNα cohort (51%) compared to the bulevirtide 2 mg (3%) and 10 mg (4%) groups. Importantly, no subjects discontinued treatment due to AEs, and there were no reports of hepatic decompensation or death in any treatment cohort.
Implications for Chronic Hepatitis Delta Treatment
The study authors concluded that the 48-week analysis of bulevirtide treatment did not identify any new safety concerns compared to previously published data. The findings support bulevirtide as a well-tolerated and safe monotherapy option for CHD, particularly in comparison to Peg-IFNα, which exhibited a less favorable safety profile in the trials.
