Final results of MYR301: a randomised phase 3 study evaluating the efficacy and safety of up to 144 weeks of bulevirtide monotherapy for chronic hepatitis Delta and 96 weeks of posttreatment follow-up

Introduction: Bulevirtide (BLV) 2 mg/day (d) is approved in Europe, Australia, and Russia for the treatment of compensated chronic hepatitis delta (CHD). In MYR301, a Phase 3 study evaluating BLV monotherapy for 2 to 3 years, BLV treatment was safe and effective through 144 weeks (W).

Objective: To present the final MYR301 results through follow-up at 96W after end of treatment (EOT; FU96).

Methodology: Patients (pts) with CHD and compensated liver disease (N=150) were randomised to immediate treatment with BLV 2 or 10 mg/d for 144W or to 48W of delayed treatment (DT) followed by BLV 10 mg/d for 96W (DT/10 mg) and 96W posttreatment FU. 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] 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.

Results: CR and HDV RNA undetectability rates in the 2, 10, and DT/10 mg groups decreased from EOT to FU96 ([Fig. 1]). Of the 64 pts across all groups with undetectable HDV RNA at EOT and available FU data, 23 (36%) had sustained undetectable HDV RNA through FU96, and 41 pts had viral relapse, which occurred in 38 (93%) by FU24 and none after FU48. Sustained posttreatment undetectable HDV RNA was more frequent in pts with longer on-treatment continuous HDV RNA undetectability at EOT ([Fig. 2]). Posttreatment HBsAg loss occurred in 3 pts. In the posttreatment period, 14/142 (10%) pts 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%) pts; 7 had ALT>10×ULN, 15 had HDV rebound (HDV RNA increased≥2 log₁₀ IU/mL from EOT), and 4 had liver-related hospitalisation; 1 additional pt experienced nonserious ascites. The hepatic SAEs resolved in 17/20 (85%) pts,≥16 of whom restarted BLV.

Fig. 1  

Fig. 2  

Conclusion: In pts with CHD treated with BLV monotherapy for 96W or 144W, response rates decreased after treatment discontinuation. However, a subset of pts 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 the first year after EOT and may be associated with hepatitis flares.