Bulevirtide Monotherapy Well-Tolerated, Safe for Chronic Hepatitis Delta at Week 48

Credit: Pexels

Bulevirtide monotherapy is both safe and well-tolerated in patients with chronic hepatitis delta (CHD) through 48 weeks of use, according to recent findings.¹

These findings resulted from a new study assessing safety and tolerability of bulevirtide, with an integrated analysis of clinical trial findings from those with chronic hepatitis delta.

This analysis was authored in part by Tarik Asselah, MD, PhD, from the department of hepatology at the Université de Paris-Cité Hôpital Beaujon. Bulevirtide was approved in Europe, and additional data was then released confirming the drug’s efficacy and safety.²

“In this integrated analysis of data derived from completed and ongoing clinical trials, we describe the safety and tolerability of [bulevirtide] therapy after 48 weeks of treatment among patients with CHD and compensated liver disease,” Asselah and colleagues wrote.¹

Trial Design

The investigative team evaluated safety of bulbertide through the combination of information from 3 multi-center, open-label, randomized phase 2 and 3 clinical studies. These analyses assessed the implementation of bulevirtide for the treatment of CHD, with subjects in the trials being given either 2 mg or 10 mg of bulevirtide, pegylated interferon-alpha (Peg-IFNα) as a reference treatment, or no anti-HDV therapy as part of a delayed-treatment control group featured in the MYR301 study.

All of these treatments were administered by the team as monotherapy for a duration of 48 weeks. These studies, specifically identified as MYR203, MYR204, and MYR301, were carried out within 7 countries: Germany, Romania, Italy, France, Russia, and Sweden.

Criteria for participants to be eligible for the studies included men and women in the age range of 18 - 65 years. Additionally, other criteria were having CHD with or without compensated cirrhosis, detectable HDV RNA at the time of one's screening, and elevated ALT levels.

During the study, the investigators administered the 10 mg dose of bulevirtide as two 5 mg subcutaneous injections, maintaining the 2 mg dose as a single injection.

In terms of specific districution, the subjects were placed into 4 cohorts: bulevirtide 2 mg (64 individuals), bulevirtide 10 mg (115 individuals), Peg-IFNα (39 individuals), and a delayed-treatment control arm (51 individuals).

Major Findings

The researchers found that certain adverse events (AEs) had taken place more frequently among those treated with bulevirtide compared to those in the control arm of the analyses.

The 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).

Although increases in total bile acid levels were noted by the investigators with bulevirtide, they found no clear connection between such increases and other AEs such as eosinophilia, itch, or vitamin D deficiency.

AEs labeled as Grade 3 or 4 that were observed to be connected to the study drug took place more often in the Peg-IFNα cohort (51%) compared to participants receiving bulevirtide 2 mg (3%) or 10 mg (4%).

Notably, no serious AEs were found to be linked to bulevirtide therapy. They added that no subjects discontinued the treatment resulting from AEs. Additionally, there were no cases of hepatic decompensation and no cases of death reported in any of the treatment cohorts.

“In conclusion, this integrated analysis of [bulevirtide] treatment through 48 weeks did not identify any new safety concerns associated with [bulevirtide] monotherapy at either dosage relative to previously published data,” they wrote. “[Bulevirtide] has been shown to demonstrate a consistent and predictable tolerability and safety profile, which is more favourable than Peg-IFNα alone.”¹

References

1. ^{Asselah, T., Lampertico, P., Aleman, S., Bourlière, M., Streinu-Cercel, A., Bogomolov, P., Morozov, V., Stepanova, T., Lazar, S., Manuilov, D., Mercier, R.-C., Tseng, S., Ye, L., Flaherty, J.F., Osinusi, A., Da, B.L., Chee, G.M., Lau, A.H., Brunetto, M.R. and Wedemeyer, H. (2024), Bulevirtide Monotherapy Is Safe and Well Tolerated in Chronic Hepatitis Delta: An Integrated Safety Analysis of Bulevirtide Clinical Trials at Week 48. Liver Int. https://doi.org/10.1111/liv.16174.}
2. ^{E. Degasperi, M. P. Anolli, S. C. Uceda Renteria, et al., “Bulevirtide Monotherapy for 48 Weeks in Patients With HDV-Related Compensated Cirrhosis and Clinically Significant Portal Hypertension,” Journal of Hepatology 77, no. 6 (2022): 1525–1531.}