Efficacy and safety of bulevirtide monotherapy given at 2-mg or 10-mg dose level once daily for treatment of chronic hepatitis delta: Week 48 primary endpoint results from a Phase 3 randomized, multicenter, parallel design study

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Introduction Bulevirtide (BLV) is a first-in-class entry inhibitor for the treatment of chronic hepatitis delta virus infection (CHD) that was conditionally approved in the EU in July 2020 based on Phase 2 data. In an interim 24-week analysis of a Phase 3 study (MYR301; NCT03852719), monotherapy with BLV at 2 mg or 10 mg once daily demonstrated a significantly greater combined virologic/biochemical response compared with control and had a favorable safety profile. Objectives Here, we present findings for the week 48 primary endpoint analysis of the MYR301 study. Methodology Patients with CHD (n=150) were randomized to 3 treatment groups and stratified based on compensated cirrhosis status: Arm A (n=51), no active anti-CHD treatment for 48 weeks followed by BLV 10 mg/d for 96 weeks; Arms B or C, immediate treatment with BLV at 2 mg/d (n=49) or 10 mg/d (n=50), respectively, each for 144 weeks. All arms then entered treatment-free follow-up for 96 weeks. The primary endpoint was combined response, defined as undetectable HDV RNA or decrease by≥2 log 10 IU/mL from baseline and alanine aminotransferase (ALT) normalization at week 48. Other endpoints included viral response (undetectable HDV RNA or decrease by≥2 log 10 IU/mL from baseline), ALT normalization, change in HDV RNA levels, and change in liver stiffness. Results Owing to a communications embargo, week 96 data were not available for this submission. We will include those data for presentation of this at the DGVS conference. Baseline characteristics: mean (SD) age, 41.8 (8.4) years; 57.3% males; 82.7% White; 47.3% with compensated cirrhosis; 60% on nucleos(t)ide analogues therapy; mean (SD) HDV RNA, 5.05 (1.35) log 10 IU/mL; mean (SD) ALT, 110.9 (69.0) U/L. At week 48, combined response rates were similar in both BLV arms and significantly greater than in the control arm ([ Abb. 1 ]; P <.0001). Viral and biochemical response rates were also similar in the BLV arms and significantly greater than control ( P <.0001). BLV was safe and well tolerated during the 48-week treatment period. No adverse events (AEs) led to BLV discontinuation, and no serious AEs were attributed to BLV treatment. Asymptomatic elevations in total serum bile salts and injection-site reactions occurred at a higher frequency with the BLV 10-mg dose level. Abb. 1 Conclusion At week 48, BLV resulted in a significantly greater combined response rate compared with control and was safe and well tolerated. Publication History Article published online: 28 August 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

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