Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection

作者：Man‐Fung Yuen, Seng Gee Lim, Robert Pleśniak, Keiji Tsuji, Harry L.A. Janssen, Cristina Pojoga, Adrián Gadano, Corneliu Petru Popescu, Tatyana Stepanova, Tarik Asselah, Gheorghe Diaconescu, Hyung Joon Yim, Jeong Heo, Ewa Janczewska, Alexander Wong, Nevin Idriz, Michio Imamura, Giuliano Rizzardini, Koichi Takaguchi, Pietro Andreoné, Manuela Arbune, Jinlin Hou, Sung Jae Park, A Vâţă, Jennifer Cremer, Robert C. Elston, Tamara Lukić, Geoff Quinn, Lauren Maynard, Stuart Kendrick, Helene Plein, Fiona Campbell, Melanie Paff, Dickens Theodore · 发表于：New England Journal of Medicine · 年份：2022 · DOI：10.1056/nejmoa2210027 · 被引用次数：275 · 研究领域：Hepatitis B Virus Studies、Hepatitis C virus research、Hepatitis Viruses Studies and Epidemiology

BACKGROUND: Bepirovirsen is an antisense oligonucleotide that targets all hepatitis B virus (HBV) messenger RNAs and acts to decrease levels of viral proteins. METHODS: We conducted a phase 2b, randomized, investigator-unblinded trial involving participants with chronic HBV infection who were receiving or not receiving nucleoside or nucleotide analogue (NA) therapy. Participants were randomly assigned (in a 3:3:3:1 ratio) to receive weekly subcutaneous injections of bepirovirsen at a dose of 300 mg for 24 weeks (group 1), bepirovirsen at a dose of 300 mg for 12 weeks then 150 mg for 12 weeks (group 2), bepirovirsen at a dose of 300 mg for 12 weeks then placebo for 12 weeks (group 3), or placebo for 12 weeks then bepirovirsen at a dose of 300 mg for 12 weeks (group 4). Groups 1, 2, and 3 received loading doses of bepirovirsen. The composite primary outcome was a hepatitis B surface antigen (HBsAg) level below the limit of detection and an HBV DNA level below the limit of quantification maintained for 24 weeks after the planned end of bepirovirsen treatment, without newly initiated antiviral medication. RESULTS: The intention-to-treat population comprised 457 participants (227 receiving NA therapy and 230 not receiving NA therapy). Among those receiving NA therapy, a primary-outcome event occurred in 6 participants (9%; 95% credible interval, 0 to 31) in group 1, in 6 (9%; 95% credible interval, 0 to 43) in group 2, in 2 (3%; 95% credible interval, 0 to 16) in group 3, and 0 (0...