Bulevirtide monotherapy is safe and well tolerated in patients with chronic hepatitis D (CHD): An integrated safety analysis of 48-week data. (March 2023)

• Record Type: Journal Article
• Authors: Asselah, T.; Lampertico, P.; Aleman, S.; Bourliere, M.; Streinu-Cercel, A.; Bogomolov, P.; Morozov, V.; Stepanova, T.; Lazar, S.; Suri, V.; Manuilov, D.; Mercier, R.C.; Tseng, S.; Ye, L.; Flaherty, J.F.; Osinusi, A.; Brunetto, M.; Wedemeyer, H.
• Is Part Of: Digestive and liver disease. Volume 55(2023)Supplement 1
• Page Start: S74
• Publication Date: 2023-03
• Subjects: Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; 616.33005
• DOI: 10.1016/j.dld.2023.01.145
• Languages: English
• ISSNs: 1590-8658

Abstract

Abstract : Introduction: Bulevirtide (BLV), a novel first-in-class entry inhibitor of the hepatitis delta virus (HDV) that was conditionally approved for treatment of chronic HDV (CHD) in the EU in July 2020, was generally safe and well tolerated in Phase 2 (MYR 203, NCT02888106 and MYR 204, NCT03852433) and Phase 3 (MYR301, NCT03852719) studies. Aim: We present an integrated safety analysis of 48-week (48W) data from these studies. Methods and Results: In a pooled analysis, treatment-emergent adverse events (AEs), serious adverse events (SAEs), discontinuations, and laboratory abnormalities were assessed in patients treated with BLV alone at 2 or 10 mg for 48W, compared with patients receiving no active anti-HDV treatment (control) and those receiving the current standard of care (SOC; pegylated-interferon alfa [Peg-IFNα]). A total of 269 patients with CHD were included; the baseline demographics of all groups were well balanced. At 48W, overall incidence of AEs was similar in BLV 2 and 10 mg groups at 85.9% and 86.1%, respectively, compared with rates of 89.7% with Peg-IFNα and 76.5% for controls. There were no BLV-related SAEs and no AEs leading to BLV discontinuation. AE profiles were similar between BLV and control groups, with a few exceptions, including higher rates of headache, injection-site reactions (ISRs), pruritus, fatigue, dizziness, nausea, and eosinophilia in the BLV groups. As expected, asymptomatic dose-dependent increases in serum bile acids were observed. Most AEs were mild/moderate in severity. ISRs were more common in the BLV 10 mg group (who received 2 daily subcutaneous injections) vs 2 mg. BLV safety did not differ between patients with and without cirrhosis. Conclusion: BLV 2 mg monotherapy was safe and well tolerated through 48W, including among patients with compensated cirrhosis and those previously exposed to interferon. The frequency of AEs was similar with both BLV dosages and lower compared to SOC.