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

Bulevirtide (BLV) was conditionally approved in the EU for the treatment of chronic hepatitis D virus (HDV) infection (CHD). A 24-week (W) analysis of a Phase 3 study (MYR301; NCT03852719) of BLV 2 or 10 mg QD demonstrated significantly greater combined virologic/biochemical response (CR) vs control and favorable safety. Patients with CHD (N=150) were randomized 1:1:1: Arm A (control), no active anti-HDV treatment for 48W followed by BLV 10 mg for 96W (n=51); Arms B and C, BLV 2 (n=49) or 10 mg (n=50), respectively, for 144W. All arms then entered a 96W treatment-free follow-up. Primary endpoint: CR (undetectable HDV RNA or decrease by≥2 log10 IU/mL from baseline and ALT) at 48W. Other endpoints included viral response, biochemical response, and change in liver stiffness. 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; mean (SD) HDV RNA, 5.05 (1.35) log10 IU/mL; mean (SD) ALT, 110.9 (69.0) U/L. CR was achieved by 22 (44.9%) and 24 (48.0%) patients in Arms B and C vs 1 (2.0%) in Arm A (P<.0001). Viral and biochemical response rates were similar in both BLV arms and significantly greater than control at W48 (P<.0001). No adverse events led to BLV discontinuation; no serious adverse events were attributed to BLV. Asymptomatic total serum bile salt elevations and injection-site reactions occurred more frequently with BLV 10 mg. BLV treatment resulted in a significantly greater CR vs control and was well-tolerated at W48.