Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients
- Author:
Jinlin HOU
1
;
Edward GANE
;
Rozalina BALABANSKA
;
Wenhong ZHANG
;
Jiming ZHANG
;
Tien Huey LIM
;
Qing XIE
;
Chau-Ting YEH
;
Sheng-Shun YANG
;
Xieer LIANG
;
Piyawat KOMOLMIT
;
Apinya LEERAPUN
;
Zenghui XUE
;
Ethan CHEN
;
Yuchen ZHANG
;
Qiaoqiao XIE
;
Ting-Tsung CHANG
;
Tsung-Hui HU
;
Seng Gee LIM
;
Wan-Long CHUANG
;
Barbara LEGGETT
;
Qingyan BO
;
Xue ZHOU
;
Miriam TRIYATNI
;
Wen ZHANG
;
Man-Fung YUEN
Author Information
- Publication Type:Original Article
- From:Clinical and Molecular Hepatology 2024;30(2):191-205
- CountryRepublic of Korea
- Language:EN
-
Abstract:
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-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.
Results: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.
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.
