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

Background/Aims Bulevirtide (BLV) is a novel, first‐in‐class entry inhibitor that is conditionally EMA approved for the treating chronic hepatitis delta virus (HDV) infection (CHD). A prespecified interim 24‐week (W) analysis of a Phase 3 study (MYR301; NCT03852719) showed that significantly greater proportions of patients treated with BLV monotherapy 2 or 10mg qd achieved combined virologic/biochemical response vs control. W48 findings from the MYR301 primary endpoint analyses are presented. Methods 150 patients with CHD were randomized 1:1:1 and stratified by compensated‐ cirrhosis status: Arm A (control) received no active anti‐HDV treatment for 48W followed by BLV 10mg/d for 96W (n=51); Arms B and C received BLV 2mg/d (n = 49) or 10mg/d (n = 50) for 144W. After 144W, all patients entered a 96W treatment‐free follow‐ up. The primary endpoint was undetectable HDV RNA or decrease by ≥2 log10 IU/mL from baseline and alanine aminotransferase (ALT) normalization at W48. Other endpoints included viral response (undetectable HDV RNA or decrease by ≥2 log10 IU/mL from baseline), biochemical response (ALT normalization), change in HDV RNA, and change in liver stiffness. Safety was assessed by lab parameters and adverse event (AE) reporting. Results Baseline characteristics included mean (SD) age, 41.8 (8.4) years; 57.3% males; 82.7% White; 47.3% compensated cirrhosis; 60.0% on nucleos(t)ide analogues; HDV RNA mean (SD), 5.04 (1.35) log10 IU/mL; ALT mean (SD), 110.9 (69.0) U/L. At W48, proportions with combined, viral, and biochemical responses were similar in both BLV arms and were significantly greater vs controls (P <.0001). No AEs led to BLV discontinuation, and no serious AEs were attributed to BLV. Asymptomatic elevations in total serum bile acids and injection‐ site reactions occurred more frequently with BLV 10mg than with BLV 2mg. Conclusion BLV monotherapy resulted in a significantly greater combined response vs control and was well tolerated. (Figure Presented) .