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KMID : 1040620240300020191
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Clinical and Molecular Hepatology
2024 Volume.30 No. 2 p.191 ~ p.205
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Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients
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Jinlin Hou
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
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Abstract
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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-naive 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-naive 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-naive patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naive 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.
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KEYWORD
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Linvencorvir, RO7049389, Capsid assembly modulator, Chronic hepatitis B, Phase 2
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