S2693 Final Results of MYR301: A Randomized Phase 3 Study Evaluating the Efficacy and Safety of Up to 144 Weeks of Bulevirtide Monotherapy for Chronic Hepatitis Delta and 96 Weeks of Post-Treatment Follow-Up

Introduction: Bulevirtide (BLV) 2 mg/day (d) is approved in Europe, Australia, and Russia for treatment of compensated chronic hepatitis delta (CHD). In MYR301, a Phase 3 study evaluating BLV monotherapy for 2–3 years, BLV was safe and effective through 144 weeks (W). We present final MYR301 results through follow-up at 96 W posttreatment (FU96). Methods: Patients (patients) with compensated CHD (N = 150) were randomized to immediate treatment with BLV 2 or 10 mg/d for 144 W or to 48 W of delayed treatment (DT) followed by BLV 10 mg/d for 96 W (DT to 10 mg) and FU96. Efficacy endpoints included virologic response (VR; undetectable hepatitis delta virus [HDV] RNA or ≥2 log10 IU/mL decline from baseline), combined response (CR; VR and alanine aminotransferase [ALT] normalization), ALT normalization, undetectable HDV RNA, and hepatitis B surface antigen (HBsAg) loss. The primary analysis was intention to treat with missing data considered failures. Results: Most patients (92%) remained in the study at the end of treatment (EOT); 72% and 57% completed FU48 and FU96, respectively. CR rates in the 2, 10, and DT to 10 mg groups, respectively, declined from 57%, 54%, and 56% at EOT to 24% in each group at FU96. HDV RNA undetectability rates were 29%, 50%, and 52% at EOT and 20%, 22%, and 20% at FU96. Of the 64 patients with undetectable HDV RNA at EOT and FU data, 23 (36%) had sustained undetectable HDV RNA through FU96, and 41 patients had viral relapse, which occurred in 38 (93%) by FU24 and none after FU48. Sustained posttreatment HDV RNA undetectability was more frequent in patients with longer on-treatment continuous undetectability at EOT: 9/10 (90%) for ≥96 W, 11/22 (50%) for ≥48 W to <96 W, and 3/32 (9%) for 0 W to <48 W. Posttreatment HBsAg loss occurred in 3 patients. In the posttreatment period, 14/142 (10%) patients had ALT >10 × the upper limit of normal (ULN), which occurred by FU24 in most (10/14, 71%). Posttreatment hepatic serious adverse events (SAEs) were reported in 20/142 (14%) patients: 7, ALT >10 × ULN; 4, liver-related hospitalization; 1, nonserious ascites. The hepatic SAEs resolved in 17/20 (85%) patients, ≥16 of whom restarted BLV. Conclusion: In patients with CHD treated with BLV monotherapy for 96 W or 144 W, response rates decreased after treatment discontinuation. Some patients maintained undetectable HDV RNA for 2 years posttreatment. Only in the first year after EOT was posttreatment viral relapse observed, which may be associated with hepatitis flares.