IDDF2024-ABS-0266 Efficacy and safety at 96 weeks of bulevirtide 2mg or 10 mg monotherapy for chronic hepatitis D (CHD): results from an interim analysis of a phase 3 randomized study

Background Bulevirtide (BLV) is conditionally approved in the EU for the treatment of chronic hepatitis D (CHD) based on surrogate endpoint results. Virologic responders (VR) to HDV therapy are defined as achieving undetectability or a ≥2-log10 IU/mL decline in HDV RNA from baseline (BL). However, it is unclear if patients who are early virologic nonresponders (NR) will benefit from continued therapy. Methods MYR301 is a randomized study: BLV 2mg (Arm B) and BLV 10mg (Arm C) for 144W. Results from participants on treatment at 96W from Arm B + C were included in this analysis. Rates of participants achieving biochemical response (alanine transaminase ALT within normal limits WNL) were compared between NR, PR, and VR. Results Baseline characteristics were similar between groups and included: mean (SD) age 41.8 (8.4) years, 57% males, 83% White, 47% with compensated cirrhosis, mean (SD) HDV RNA 5.05 (1.34) log10 IU/mL, mean (SD) ALT 110.9 (69.0) U/L, mean (SD) LS of 15 (8.9) kPa; and 61% were on concomitant nucleos(t)ide analogues therapy. Of 150 patients, 143 (95%) completed 96 weeks of treatment. Week 96 efficacy responses were improved vs. Week 48 (IDDF2024-ABS-0266 Table 1). At Week 96, similar combined responses were seen in arms B and C. Viral and biochemical responses were also similar among arms B and C. BLV were safe and well tolerated; there were no drug discontinuations, serious AE (SAE) or deaths attributed to BLV. Increases in bile acids without a correlation to pruritus or other symptoms were noted with BLV treatment. Injection site reactions occurred in a higher proportion receiving 10 mg/d dosing. Conclusions Most patients who were PR (75%) and a considerable portion who were NR (43%) to BLV at 24W achieved VR by W96, with ALT improvements occurring in all groups, including those who remained NR.