Background Bulevirtide (BLV) is a first-in-class entry inhibitor for chronic hepatitis D (CHD) which was conditionally approved in the EU. Results from the Week 48 primary endpoint analysis for MYR301, a phase 3 randomized study, showed monotherapy with BLV at 2 or 10 mg/d given subcutaneously was superior to no active anti-HDV treatment e. Here, we present findings from the predefined week 96 interim analysis of this ongoing study.

Methods 150 patients with CHD were randomized and stratified: Arm A: no active anti-HDV treatment for 48 weeks followed by BLV 10mg/d for 96 weeks (n=51), and 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, with follow-up of 96 weeks after end of treatment. The combined response was defined as undetectable HDV RNA or decrease by ≥2 log10 IU/mL from baseline and ALT normalization; other endpoints included viral response, ALT normalization, log10 change in HDV RNA and change in liver stiffness by transient elastography.

Results At W24, 62% of participants were VR, of which 30 had ALT WNL, 22 were PR, of which 12 had ALT WNL, and 14 were NR, of which 2 had ALT WNL. (IDDF2024-ABS-0267 Table 1) Of the 36 NR or PR at W24 vs VR, mean baseline HDV RNA and median ALT at W96 were as follows: VR [5.1 log10 IU/mL, 77 U/mL], PR [4.9 log10 IU/mL, 120 U/mL], and NR [4.4 log10 IU/mL, 156 U/mL]. Of 22 PR participants at W24, 18 became VR by W96; 15 with ALT WNL) and 3 remained PR; 2 with ALT WNL.

Conclusions BLV continues to be safe and well tolerated as monotherapy for CHD through Week 96. Virological and biochemical responses increased with longer-term therapy.