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In the Phase 3 MYR301 study, a subset of patients with chronic hepatitis delta (CHD) receiving bulevirtide (BLV) monotherapy achieved undetectable hepatitis delta virus (HDV) RNA by end of treatment (EOT, 2–3 years) and maintained undetectable viraemia at follow-up (FU) 48 weeks (W) after EOT. We present predictors of sustained HDV RNA undetectability through FU48 after 96W or 144W of BLV treatment.Patients with CHD (n=149) in MYR301 were randomised to treatment with BLV 2 or 10 mg/day for 144W, or delayed treatment for 48W followed by BLV 10 mg/day for 96W (DT-to-10 mg). All patients were to be followed through FU48. Logistic regression modelling (adjusted for treatment group) was evaluated via odds ratios (OR [95% CI]) for potential predictors of sustained HDV RNA undetectability (defined as less than the lower limit of quantitation [target not detected at follow-up]) through FU48 in those with undetectable viraemia at EOT.Baseline characteristics were similar between treatment arms. Overall, 65/149 (44%) patients achieved HDV RNA undetectability at EOT, of whom 23/64 (36%) had sustained undetectability through FU48. Sustained undetectability rates were higher in the immediate treatment (2 mg: 7/14, 50%; 10 mg: 10/25, 40%) vs DT-to-10 mg arms (6/26, 23%). Undetectability rates at EOT were higher in the BLV 10 mg arm, but relapse was less frequent among the few patients with HDV RNA undetectable in the BLV 2 mg arm. Baseline predictors of sustained undetectability posttreatment included baseline median HDV RNA <4.5 log1 0 IU/mL (OR [95% CI]: 6.2 [1.9, 20.8]; P=0.003) and lower baseline hepatitis B surface antigen (HBsAg) level (0.3 per log1 0 IU/mL [0.1, 0.8]; P=0.019). On-treatment predictors included greater duration of continuous undetectability at EOT (per additional week: 1.0 [1.0, 1.1]; P<0.0001), HBsAg loss or decrease by ≥1 log1 0 IU/mL (7.2 [1.2, 42.3]; P=0.030), and W144 antidrug antibody (ADA) incidence (10.2 [1.9, 55.7]; P=0.008). The proportion of patients with sustained posttreatment undetectability was highest (9/10 [90%]) in those with ≥96W of undetectability at EOT, 11/22 (50%) in those with ≥48 to <96W, and 3/32 (9%) in those with <48W. Of patients with ADA incidence by W144, 8/10 (80%) had sustained undetectability vs 15/54 (28%) of those without. Baseline cirrhosis was not a predictor of sustained posttreatment undetectability (13/32 [41%] with vs 10/32 [31%] without cirrhosis).In patients with CHD treated with BLV monotherapy for 96W or 144W, early and sustained HDV RNA undetectability predicted sustained undetectability during follow-up.