S2695 Predictors of Undetectable Hepatitis Delta Virus RNA at 48 Weeks After End of Treatment With Bulevirtide Monotherapy in the MYR 301 Study

Introduction: In the MYR301 Phase 3 study, a subset of patients (patients) with chronic hepatitis delta (CHD) receiving bulevirtide (BLV) monotherapy achieved undetectable HDV RNA by end of treatment (EOT, 2–3 years) and maintained undetectable viremia at 48 weeks (W) after EOT (FU48). We present predictors of sustained HDV RNA undetectability through FU48 after 96W or 144 W of BLV treatment. Methods: Pts with CHD in MYR301 (n = 149) were randomized to immediate treatment with BLV 2 or 10 mg/d for 144 W, or delayed treatment for 48 W followed by BLV 10 mg/d for 96W (DT/10 mg) and 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 < the lower limit of quantitation [LLOQ; target not detected at FU]) through FU48 in patients with undetectable viremia at EOT. Results: Baseline (BL) characteristics were similar between treatments. Overall, 65/149 (44%) patients achieved HDV RNA undetectability at EOT; 23/64 (36%) with FU data sustained undetectability through FU48. Sustained undetectability rates were higher in the immediate treatment arms (2 mg: 7/14, 50%; 10 mg: 10/25, 40%) vs the DT/10 mg (6/26, 23%) arm. Undetectability rates at EOT were higher in patients receiving BLV 10 mg; the relapse rate was lower in patients with HDV RNA < LLOQ in the BLV 2 mg group. BL predictors of sustained undetectability posttreatment (PT) included BL median HDV RNA < 4.5 log10 IU/mL (OR [95% CI]: 6.2 [1.9, 20.8]; P = .003) and lower BL hepatitis B surface antigen (HBsAg) level (0.3 per log10 IU/mL [0.1, 0.8]; P = .019). On-treatment predictors included greater duration of continuous undetectability at EOT (per additional week: 1.0 [1.0, 1.1]; P < .0001), HBsAg loss/decrease by ≥1 log10 IU/mL (7.2 [1.2, 42.3]; P = .030), and W144 antidrug antibody (ADA) incidence (10.2 [1.9, 55.7]; P = .008). The proportion of patients with sustained PT undetectability was 9/10 (90%) in patients with ≥96 W of undetectability at EOT, 11/22 (50%) in patients with ≥48 to <96 W, and 3/32 (9%) in patients with <48 W. Of patients with ADA incidence by W144, 8/10 (80%) had sustained undetectability vs 15/54 (28%) of patients without. BL cirrhosis was not a predictor of sustained PT undetectability (13/32 [41%] with vs 10/32 [31%] without cirrhosis). Conclusion: In patients with CHD treated with BLV monotherapy for 96 W or 144 W, early and sustained HDV RNA undetectability predicted undetectability at EOT and sustained undetectability during FU. PL and HW contributed equally.