Global 
Deutschland Liver and Bile
J Hepatol. 2024;81(4):621-629
Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96 from a phase 3 randomized trial
Background and aims: Bulevirtide (BLV), a first-in-class entry inhibitor, is approved in Europe for the treatment of chronic hepatitis delta (CHD). BLV monotherapy was superior to delayed treatment at week (W) 48, the primary efficacy endpoint, in the MYR301 study. Here, the authors assessed if continued BLV therapy until W96 would improve virologic and biochemical response rates, particularly among patients who did not achieve virologic response at W24.
Methods: In this ongoing, open-label, randomized phase 3 study, patients with CHD (n = 150) were randomized (1:1:1) to treatment with BLV 2 mg/day (n = 49) or 10 mg/day (n = 50), each for 144 weeks, or to delayed treatment for 48 weeks followed by BLV 10 mg/day for 96 weeks (n = 51). Combined response was defined as undetectable hepatitis delta virus (HDV) RNA or a decrease in HDV RNA by ≥ 2 log10 IU/ml from baseline and alanine aminotransferase (ALT) normalization. Other endpoints included virologic response, ALT normalization, and change in HDV RNA.
Results: Of 150 patients, 143 (95%) completed 96 weeks of the study. Efficacy responses were maintained and/or improved between W48 and W96, with similar combined, virologic, and biochemical response rates between BLV 2 and 10 mg. Of the patients with a suboptimal early virologic response at W24, 43% of non-responders and 82% of partial responders achieved virologic response at W96. Biochemical improvement often occurred independently of virologic response. Adverse events were mostly mild, with no serious adverse events related to BLV.
Conclusions: Virologic and biochemical responses were maintained and/or increased with longer term bulevirtide (BLV) therapy, including in those with suboptimal early virologic response. BLV monotherapy for chronic hepatitis delta was safe and well tolerated through week 96.