Headache, pruritis, fatigue, eosinophilia, injection-site reactions, upper abdominal pain, arthralgia, and asthenia were more common in the bulevirtide group compared to the control group.
New research indicates bulevirtide helps treat patients with chronic hepatitis D virus (HDV) infections, while not producing any new safety signals.
A team, led by Dr. Heiner Wedemeyer, Medizinische Hochschule Hannover, Excellence Cluster RESIST, and D-SOLVE Consortium, evaluated different doses of bulevirtide in patients with chronic HDV compared to a control group.
Patients with HDV coinfection often have accelerated progression of liver disease linked to chronic hepatitis B. However, 1 treatment option is bulevirtide, which inhibits the entry of HDV into hepatocytes.
In the ongoing phase 3 trial, the investigators examined patients with chronic hepatitis D with or without compensated cirrhosis. Each participant was treated with either bulevirtide subcutaneously at 2 mg per day (n = 49) or 10 mg per day (n = 50) for 144 weeks or were not treated for 48 weeks followed by bulevirtide subcutaneously 10 mg per day (n = 51) for 96 weeks as the control group.
Each patient will complete 96 weeks of follow-up after the conclusion of treatment.
The investigators sought primary endpoints of a combined response at week 48 of an undetectable HDV RNA level or a level that decreased by at least 2 log10 IU per mL from baseline and normalization of the alanine aminotransferase (ALT) level. They also looked at key secondary endpoints of an undetectable HDV RNA level at week 48 in a comparison between the 2 mg group and the 10 mg cohort.
The results show a 45% primary endpoint response in the 2 mg group, compared to a 48% response in the 10 mg group and a 2% response in the control group (P <0.001 for the comparison of each dose group with the control group).
In addition, they could not detect the HDV RNA level at week 48 in 12% of patients in the 2 mg group and 20% of patients in the 10 mg group (P = 0.41) and the ALT level normalized in 12% of the control group, 51% of the 2 mg group (difference from control, 39 percentage points; 95% confidence interval [CI], 20-56), and 56% in the 10-mg group (difference from control, 44 percentage points; 95% CI, 26-60).
The investigators found that the loss of HBV surface antigen (HBsAg) or an HBsAg level that decreased by at least 1 log10 IU per mL did not occur in the bulevirtide groups by week 48.
In the safety analysis, headache, pruritis, fatigue, eosinophilia, injection-site reactions, upper abdominal pain, arthralgia, and asthenia were more common in the bulevirtide group compared to the control group.
There were no treatment-related serious adverse events found in the study,
Finally, there were dose-dependent increases in bile acid levels in the bulevirtide groups.
“After 48 weeks of bulevirtide treatment, HDV RNA and ALT levels were reduced in patients with chronic hepatitis D,” the authors wrote.
Wedemeyer, H., Aleman, S., Brunetto, M. R., Blank, A., Andreone, P., Bogomolov, P., Chulanov, V., Mamonova, N., Geyvandova, N., Morozov, V., Sagalova, O., Stepanova, T., Berger, A., Manuilov, D., Suri, V., An, Q., Da, B., Flaherty, J., Osinusi, A., … Lampertico, P. (2023). A phase 3, randomized trial of Bulevirtide in chronic hepatitis D. New England Journal of Medicine. https://doi.org/10.1056/nejmoa2213429