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In MYR301, a Phase 3 study evaluating bulevirtide (BLV) monotherapy for 2–3 years, BLV treatment was safe and effective through 144 weeks (W) in patients with compensated chronic hepatitis delta (CHD). We present final MYR301 results through follow-up at 96W after end of treatment (EOT; FU96).Patients (N=150) were randomised to treatment with BLV 2 or 10 mg/day for 144W or to 48W of delayed treatment followed by BLV 10 mg/day for 96W (DT-to-10 mg) and 96W posttreatment FU. Efficacy endpoints included virologic response (VR; undetectable hepatitis delta virus [HDV] RNA or ≥2 log1 0 IU/mL decline from baseline), combined response (CR; VR and alanine aminotransferase [ALT] normalisation), ALT normalisation, undetectable HDV RNA, and hepatitis B surface antigen (HBsAg) loss. The primary analysis was intention to treat, with missing data considered failures.Baseline characteristics were similar across groups. Most patients (92%) remained in the study at EOT; 72% and 57% completed FU48 and FU96. CR rates in the 2, 10, and DT-to-10 mg groups declined from 57%, 54%, and 56% at EOT to 24% in each group at FU96. HDV RNA undetectability rates in these groups were 29%, 50%, and 52% at EOT and 20%, 22%, and 20% at FU96. Of the total 64 patients with undetectable HDV RNA at EOT and available FU data, 23 (36%) had sustained undetectable HDV RNA through FU96 and 41 had viral relapse, which occurred in 38 (93%) by FU24 and none after FU48. Sustained posttreatment undetectable HDV RNA was more frequent with longer on-treatment continuous HDV RNA undetectability at EOT: ≥96W, 9/10 (90%); ≥48W-to-<96W, 11/22 (50%); 0-to-<48W, 3/32 (9%). Posttreatment HBsAg loss occurred in 3 patients. Posttreatment, 14/142 (10%) patients had ALT >10 × the upper limit of normal (ULN). Posttreatment hepatic serious adverse events (SAEs) were reported in 20/142 (14%) patients: 7 had ALT >10 × ULN, 15 had HDV rebound (HDV RNA increased ≥2 log1 0 IU/mL from EOT), and 4 had liver-related hospitalisation; 1 additional patient experienced nonserious ascites. The hepatic SAEs resolved in 17/20 (85%) patients, ≥16 of whom restarted BLV.In patients with CHD treated with BLV monotherapy for 96W or 144W, response rates decreased after treatment discontinuation. However, a subset of patients maintained undetectable HDV RNA for 2 years posttreatment, which was associated with longer duration of continuous on-treatment undetectability. Posttreatment viral relapse occurred only in year 1 after EOT and may be associated with hepatitis flares.