Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2024 Apr;30(2):191-205.
doi: 10.3350/cmh.2023.0422. Epub 2024 Jan 8.

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

Jinlin Hou  1 , Edward Gane  2 , Rozalina Balabanska  3 , Wenhong Zhang  4 , Jiming Zhang  4 , Tien Huey Lim  5 , Qing Xie  6 , Chau-Ting Yeh  7 , Sheng-Shun Yang  8 , Xieer Liang  1 , Piyawat Komolmit  9 , Apinya Leerapun  10 , Zenghui Xue  11 , Ethan Chen  11 , Yuchen Zhang  12 , Qiaoqiao Xie  12 , Ting-Tsung Chang  13 , Tsung-Hui Hu  14 , Seng Gee Lim  15 , Wan-Long Chuang  16 , Barbara Leggett  17 , Qingyan Bo  11 , Xue Zhou  12 , Miriam Triyatni  18 , Wen Zhang  12 , Man-Fung Yuen  19
Affiliations
Clinical Trial

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

Jinlin Hou et al. Clin Mol Hepatol. 2024 Apr.

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.

Conclusion: 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.

Keywords: Capsid assembly modulator; Chronic hepatitis B; Linvencorvir; Phase 2; RO7049389.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest

Jinlin Hou received grants from Bristol Myers Squibb and Johnson & Johnson; and declared other financial or non-financial interests with AbbVie, Arbutus, Bristol Myers Squibb, Gilead Sciences, Johnson & Johnson, and Hoffmann-La Roche.

Edward Gane is an advisory committee or review panel member for AbbVie, Arbutus, Arrowhead, Assembly Biosciences, Availa, Clear B Therapeutics, Dicerna, Finch Therapeutics, Gilead Sciences, Janssen, Novartis, Hoffmann-La Roche, and Vir Bio; and has received speaking and teaching fees from AbbVie, Aligos, DrugFarm, Enanta, Gilead, GlaxoSmithKline, Janssen, Merck, and Novartis.

Sheng-Shun Yang has received speaking fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Ipsen, and Merck Sharp & Dohme, and served as an advisory board member for AbbVie, Gilead Sciences, Hoffmann-La Roche, Sysmex, and Ipsen.

Seng Gee Lim received payment or honoraria for lectures from Gilead, Janssen, Hoffman-La Roche, Sysmex and GSK; served as advisory board member for Gliead, Abbot, Hoffmann-La Roche, GSK, Janssen, Sysmex, Abrutus, Assembly, and Grifols; served in leadership role in ICE-HBV, HBV Forum, AASLD Asia Pacific Advisory Board, and ANRS-MIE Advisory Board; and receipt of research support from Gilead, Abbot, Hoffmann-LaRoche, Sysmex, Fibronostics, and Merck.

Man-Fung Yuen serves as advisory board member/ consultant for and/or received research funding from AbbVie, Aligos Therarpeutics, AiCuris, Antios Therapeutics, Arrowhead Pharmaceuticals, Arbutus Biopharma, Assembly Biosciences, Bristol Myer Squibb, Bluejay Therapeutics, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio Incorporation, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Merck Sharp and Dohme, and Hoffmann-La Roche, Vir Biotechnology.

Rozalina Balabanska, Wenhong Zhang, Jiming Zhang, Tien Huey Lim, Qing Xie, Chau-Ting Yeh, Xieer Liang, Piyawat Komolmit, Apinya Leerapun, Ting-Tsung Chang, Tsung-Hui Hu, Wan-Long Chuang, and Barbara Leggett declare no competing interests.

Zenghui Xue, Ethan Chen, Yuchen Zhang, Qiaoqiao Xie and Wen Zhang are employees of Hoffmann-La Roche. Qingyan Bo and Xue Zhou were former employees of Hoffmann-La Roche.

Figures

Figure 1.
Figure 1.
Study design. NUC, nucleos(t)ide analogue; HBV, hepatitis B virus; LLOQ, lower limit of quantification; CHB, chronic hepatitis B; QD, once a day; NUC, nucleos(t)ide analogue; Peg-IFN, pegylated interferon; HBsAg, hepatitis B surface antigen.
Figure 2.
Figure 2.
Trial profile.
Figure 3.
Figure 3.
Mean HBV DNA levels over 72 weeks. (A) Three cohorts overall and (B) HBeAg-positive and HBeAg-negative subgroups of treatment-naïve patients in Cohorts B and C. *Excluded one non-compliant patient during the FU period. **One patient was retreated with NUC from Week 60. Error bars represent standard deviation. HBV, hepatitis B virus; EOT, end of treatment; FU, follow-up; NUC, nucleos(t)ide analogue; Peg-IFN, pegylated interferon.
Figure 4.
Figure 4.
Mean HBV RNA levels over 72 weeks. Error bars represent standard deviation. HBV, hepatitis B virus; EOT, end of treatment; LLOQ, lower limit of quantification; NUC, nucleos(t)ide analogue; Peg-IFN, pegylated interferon.
Figure 5.
Figure 5.
HBsAg (A), HBeAg (B) and HBcrAg (C) mean changes from baseline* over 72 weeks. *Patients with baseline value below the LLOQ were excluded from change from baseline analysis. HBsAg ≥4 log means baseline HBsAg level ≥4 log10 IU/mL; HBsAg <4 log means baseline HBsAg level <4 log10 IU/mL. Error bars represent standard deviation. EOT, end of treatment; HBsAg, hepatitis B surface antigen; HBcrAg, hepatitis B core-related antigen; LLOQ, lower limit of quantification; NUC, nucleos(t)ide analogue.
None
See this image and copyright information in PMC

Comment in

References

    1. GBD 2019 Hepatitis B Collaborators Global, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Gastroenterol Hepatol. 2022;7:796–829. - PMC - PubMed
    1. World Health Organization (WHO) Hepatitis B. WHO Fact sheets. WHO web site, < https://www.who.int/news-room/fact-sheets/detail/hepatitis-b>. Accessed 18 Jul 2023.
    1. Lok AS, Zoulim F, Dusheiko G, Ghany MG. Hepatitis B cure: From discovery to regulatory approval. J Hepatol. 2017;67:847–861. - PubMed
    1. Anderson RT, Choi HSJ, Lenz O, Peters MG, Janssen HLA, Mishra P, et al. Association between seroclearance of hepatitis B surface antigen and long-term clinical outcomes of patients with chronic hepatitis B virus infection: Systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2021;19:463–472. - PubMed
    1. European Association for the Study of the Liver EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370–398. - PubMed

Publication types

LinkOut - more resources