Continued treatment of early nonresponder or partial virologic responders with bulevirtide monotherapy in patients with chronic hepatitis delta (chd) through week 96 leads to improvement in virologic and biochemical responses

Bulevirtide (BLV), a novel entry inhibitor of hepatitis delta virus, is conditionally approved in Europe for treatment of CHD, yet optimal treatment duration and the potential benefit of continued treatment for early virologic nonresponders (NR) are unclear. We evaluated the efficacy of continued BLV monotherapy in those who were partial responders (PR) or NR after 24 weeks (W) of treatment. MYR301 (NCT03852719) is an ongoing, open-label, randomized Phase 3 study that compared BLV 2 and 10 mg for 144W to a delayed-treatment arm. Only results from participants treated to W96 with BLV 2 or 10 mg are included in this analysis. Virologic responders (VR) had undetectable or ≥2-log10 IU/mL decline in hepatitis delta RNA from baseline. NR and PR were defined as having HDV RNA declines of <1-log10 IU/mL and ≥1 but <2-log10 IU/mL, respectively. Rates of biochemical response (alanine transaminase [ALT] within normal limits [WNL]) were compared. Ninety-four participants were included 47 BLV 2 mg; 47 BLV 10 mg. Baseline characteristics included 62% male; 85% White; 48% with cirrhosis; 61% taking concomitant nucleos(t)ide analogues; 55% with prior interferon exposure; mean (SD) HDV RNA 5.0 (1.3) log10 IU/mL; median (Q1, Q3) ALT 102 (65, 141) U/mL. At W24, 58 (62%) participants were VR, of whom 30 had ALT WNL; 22 were PR, 12 with ALT WNL; 14 were NR, 2 with ALT WNL (table 1). Among the 36 NR or PR at W24 vs VR, mean (SD) BL HDV RNA and median (Q1, Q3) ALT at W96 were NR, 4.4 (1.9) log10 IU/mL, 156 (133, 196) U/mL; PR, 4.9 (1.4) log10 IU/mL, 120 (52, 153) U/mL; VR, 5.1 (1.7) log10 IU/mL, 77 (58, 113) U/mL. By W96, 18 of 22 W24 PR became VR, and 15 had ALT WNL, while 6 of 14 W24 NR became VR and 3 became PR. Mean (SD) HDV RNA decline from baseline at W96: VR, −3.6 (1.1) log10 IU/mL; PR, −1.5 (0.3) log10 IU/mL; NR, −0.2 (0.5) log10 IU/mL. Median (Q1, Q3) ALT decline from baseline at W96: VR, −48 (−75, −12) U/mL; PR, −42 (−102, 9) U/mL; NR, −83 (−102, −33) U/mL. At W96, ALT had declined by >50% from BL in 5 of 6 NR (1 achieved ALT WNL). Many patients who were PR (18 of 22; 82%) and who were NR (6 of 14; 43%) to BLV at W24 achieved VR by W96, with ALT improvements evident in all groups—including NR.