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.