Predictors of undetectable hepatitis delta virus RNA at 48 weeks after end of treatment with bulevirtide monotherapy in the MYR301 study

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Introduction: In MYR301, a Phase 3 study evaluating bulevirtide (BLV) monotherapy for treatment of chronic hepatitis delta (CHD) for 2–3 years, a subset of patients who achieved undetectable hepatitis delta virus (HDV) RNA by end of treatment (EOT) maintained undetectable viraemia at 48 weeks (W) of follow-up after EOT (FU48). Objectives: To evaluate predictors of sustained HDV RNA undetectability through FU48 after 96W or 144W of BLV treatment. Methodology: Data were analysed from 149 patients in MYR301 who were randomised to immediate treatment with BLV 2 or 10 mg/d for 144W, or to 48W of no treatment followed by BLV 10 mg/d for 96W. All patients were to be followed through FU48. Logistic regression modelling (adjusted for treatment group) was performed to examine potential predictors of sustained HDV RNA undetectability (defined as less than the lower limit of quantitation [target not detected at FU in patients with available data]) through FU48 in those with undetectable viraemia at EOT. Results: Baseline (BL) characteristics were similar across arms. Overall, 65/149 (44%) patients achieved undetectable HDV RNA at EOT, of whom 23/64 (36%) with available FU HDV RNA data had sustained undetectability through FU48. Sustained undetectability rates were higher in the immediate treatment arms vs the delayed treatment arm. BL predictors of sustained undetectability posttreatment (PT) included BL HDV RNA less than a median of 4.5 log 10 IU/mL (odds ratio [OR]: 6.2; 95% CI [1.9, 20.8]; P =.003) and lower BL hepatitis B surface antigen (HBsAg) level (OR: 0.3 per log 10 IU/mL; 95% CI [0.1, 0.8]; P =.019). On-treatment predictors included greater duration of continuous undetectability at EOT (OR per additional week: 1.0; 95% CI [1.0, 1.1]; P <.0001), HBsAg loss or decrease by≥1 log 10 IU/mL (OR: 7.2; 95% CI [1.2, 42.3]; P =.030), and W144 antidrug antibody incidence (OR: 10.2; 95% CI [1.9, 55.7]; P =.008). Proportions of patients with sustained PT undetectability were 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. BL cirrhosis was not a predictor of sustained PT undetectability; 13/32 (41%) with cirrhosis had sustained undetectability vs 10/32 (31%) without cirrhosis. Conclusion: In patients with CHD treated with BLV monotherapy for 96W or 144W, early and sustained HDV RNA undetectability predicted sustained undetectability during FU. Note: PL and HW contributed equally. Publication History Article published online: 04 September 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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