Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients

Background/Aims: Four -week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti -viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48 -week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non -randomized, non -controlled, open -label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment -na & iuml; ve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-alpha (Peg-IFN-alpha). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment -na & iuml; ve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment -na & iuml; ve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment -na & iuml; ve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1-2, and no linvencorvir-related serious adverse events were reported. Conclusions: 48 -week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48 -week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient. (Clin Mol Hepatol 2024;30:191-205)