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

• Published in: Clinical and molecular hepatology Vol. 30; no. 2; pp. 191 - 205
• Main Authors: Hou, Jinlin, Gane, Edward, Balabanska, Rozalina, Zhang, Wenhong, Zhang, Jiming, Lim, Tien Huey, Xie, Qing, Yeh, Chau-Ting, Yang, Sheng-Shun, Liang, Xieer, Komolmit, Piyawat, Leerapun, Apinya, Xue, Zenghui, Chen, Ethan, Zhang, Yuchen, Xie, Qiaoqiao, Chang, Ting-Tsung, Hu, Tsung-Hui, Lim, Seng Gee, Chuang, Wan-Long, Leggett, Barbara, Bo, Qingyan, Zhou, Xue, Triyatni, Miriam, Zhang, Wen, Yuen, Man-Fung
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Association for the Study of the Liver 01.04.2024; Korean Association for the Study of the Liver; 대한간학회
• Subjects: Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Capsid; capsid assembly modulator; chronic hepatitis b; DNA, Viral; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus - genetics; Hepatitis B, Chronic - drug therapy; Humans; Imidazoles; linvencorvir; Original; phase 2; Polyethylene Glycols; Pyrazines; RNA - therapeutic use; ro7049389; Standard of Care; Treatment Outcome; 내과학; Phase 2; Capsid assembly modulator; Chronic hepatitis B; RO7049389; Linvencorvir
• ISSN: 2287-2728; 2287-285X; 2287-285X
• DOI: 10.3350/cmh.2023.0422

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. 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-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve 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-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve 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. 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.