Abstract

Background Bulevirtide (BLV) is a first-in-class entry inhibitor approved in the EU for the treatment of chronic HDV infection (CHD). This Phase 2 study (MYR204) evaluated the safety and efficacy of BLV with or without peginterferon alfa-2a (PegIFN) in patients with CHD and compensated liver disease. Methods 174 patients with CHD were randomized and stratified based on the absence or presence of compensated cirrhosis to receive (A) PegIFN for 48 weeks (w); (B) BLV 2mg + PegIFN or (C) BLV 10mg + PegIFN for 48w, both followed by 48w of monotherapy with BLV 2mg or 10mg, respectively; or (D) BLV 10mg for 96w. All patients were followed up for 48w after the end of treatment (EOT). The primary endpoint was sustained virologic response at W24 after EOT (SVR24), defined as undetectable HDV RNA with a predefined comparison between Arms C and D. Results Efficacy and safety results are shown in Table 1 (IDDF2024-ABS-0270 Table 1). SVR24 was achieved by 17% of Arm A, 30% of Arm B, 46% of Arm C, and 12% of Arm D (P=.0003; Arm C vs D). ALT normalization and composite endpoint at W24 after EOT were superior with BLV 10mg + PegIFN compared to monotherapy. HBsAg loss was only observed with the combination. The most common adverse events (AE) were leukopenia, neutropenia, thrombocytopenia, influenzalike illness, lymphopenia, and vitamin D deficiency. AEs observed in the BLV + PegIFN combination arms were similar to those with PegIFN monotherapy. BLV dose-dependent bile acid elevations were asymptomatic, and levels returned to baseline after EOT. 6 patients (3%) discontinued treatment; none were assessed as related to BLV. Conclusions In patients with compensated CHD, BLV in combination with PegIFN resulted in higher rates of SVR24 and ALT normalization vs BLV or PegIFN monotherapy. Combination therapy was well tolerated with AEs, which was consistent with PegIFN monotherapy.