Long-term open-label vebicorvir for chronic HBV infection: Safety and off-treatment responses

作者：Man‐Fung Yuen, Scott Fung, Xiaoli Ma, Tuan Nguyen, Tarek Hassanein, Hie‐Won Hann, Magdy Elkhashab, Ronald Nahass, James Park, Ira M. Jacobson, Walid S. Ayoub, Steven‐Huy B. Han, Edward Gane, Katie Zomorodi, Ran Yan, Julie Ma, Steven Knox, Luisa M. Stamm, Maurizio Bonacini, Frank Weilert, Alnoor Ramji, Michael Bennett, Natarajan Ravendhran, Sing Chan, Douglas T. Dieterich, Paul Y. Kwo, Eugene R. Schiff, Ho Bae, Jacob Lalezari, Kosh Agarwal, Mark Sulkowski · 发表于：JHEP Reports · 年份：2024 · DOI：10.1016/j.jhepr.2023.100999 · 被引用次数：6 · 研究领域：Hepatitis B Virus Studies、Viral Infections and Outbreaks Research、Vibrio bacteria research studies

Background & Aims: The investigational first-generation core inhibitor vebicorvir (VBR) demonstrated safety and antiviral activity over 24 weeks in two phase IIa studies in patients with chronic HBV infection. In this long-term extension study, patients received open-label VBR with nucleos(t)ide reverse transcriptase inhibitors (NrtIs). Methods: Patients in this study (NCT03780543) previously received VBR + NrtI or placebo + NrtI in parent studies 201 (NCT03576066) or 202 (NCT03577171). After receiving VBR + NrtI for ≥52 weeks, stopping criteria (based on the treatment history and hepatitis B e antigen status in the parent studies) were applied, and patients either discontinued both VBR + NrtI, discontinued VBR only, or continued both VBR + NrtI. The primary efficacy endpoint was the proportion of patients with HBV DNA <20 IU/ml at 24 weeks off treatment. Results: Ninety-two patients entered the extension study and received VBR + NrtI. Long-term VBR + NrtI treatment led to continued suppression of HBV nucleic acids and, to a lesser extent, HBV antigens. Forty-three patients met criteria to discontinue VBR + NrtI, with no patients achieving the primary endpoint; the majority of virologic rebound occurred ≥4 weeks off treatment. Treatment was generally well tolerated, with few discontinuations due to adverse events (AEs). There were no deaths. Most AEs and laboratory abnormalities were related to elevations in alanine aminotransferase and occurred during the off-treatment or Nr...