Bulevirtide Monotherapy Is Safe and Well Tolerated in Chronic Hepatitis Delta: An Integrated Safety Analysis of Bulevirtide Clinical Trials at Week 48

ABSTRACT Background and Aims The safety and tolerability of bulevirtide (BLV), a novel entry inhibitor of hepatitis delta virus, were evaluated in an integrated analysis of clinical trial results from patients with chronic hepatitis delta (CHD). Methods Week 48 on‐treatment clinical and laboratory results from two Phase 2 trials (MYR203 [NCT02888106] and MYR204 [NCT03852433]) and one Phase 3 trial (MYR301 [NCT03852719]) were pooled ( N = 269). Patients were grouped as follows: BLV 2 mg ( n = 64), BLV 10 mg ( n = 115), pegylated interferon‐alfa ( n = 39) and control ( n = 51). The control group consisted of patients assigned to the delayed treatment group in Study MYR301. Results Adverse events (AEs) that occurred more frequently with BLV 2 mg and BLV 10 mg versus control included increased total bile acid levels (20% and 17% vs. 0%), injection‐site reactions (16% and 20% vs. 0%), headache (16% and 17% vs. 0%), pruritus (11% and 10% vs. 0%) and eosinophilia (9% and 4% vs. 0%). Increases in total bile acid levels were observed with BLV without clear correlation with AEs, such as pruritus, eosinophilia or vitamin D deficiency. Grade 3 or 4 study drug–related AEs occurred in a higher proportion of patients receiving pegylated interferon‐alfa (51%) than with BLV 2 or 10 mg (3% and 4%, respectively). There were no serious AEs related to BLV, and no patients discontinued BLV due to an AE. Neither hepatic decompensation nor death occurred. Conclusions BLV monotherapy was safe and well tolerated through 48 weeks of treatment in patients with CHD. Trial Registration: NCT02888106, NCT03852433 and NCT03852719