Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection

作者：Jinlin Hou, Seng‐Gee Lim, Maria Buti, M-F Yuen, Edward Gane, Pietro Lampertico, Norah Terrault, Huy Nguyen, Hyung Joon Yim, Qing Xie, 林健梅, Yunqing Qiu, Wen-Juei Jeng, Jeong Heo, Cheng-Yuan Peng, Chien-Hung Chen, Wan‐Long Chuang, Y D Xie, Maria Hlebowicz, Nevin Idriz, Rajiv Mehta, Kosh Agarwal, M C Silva, Alex Franca, Roxana Cernat, Apinya Leerapun, Carla S. Coffin, Adrian Gadano, Pietro Andreone, Shigetoshi Fujiyama, Vasileios Sevastianos, Yuichiro Suzuki, Vlad Ratziu, Ghassan Riachi, Hartmut Stocker, Tien Huey Lim, Tarik Asselah, Yasuhito Tanaka, Jacinta Holmes, Xieer Liang, Jennifer Cremer, Tamara Lukić, Helene Plein, Geoff Quinn, Yu Tao, Melanie Paff, Dickens Theodore, Robert Elston · 发表于：New England Journal of Medicine · 年份：2026 · DOI：10.1056/nejmoa2515131 · 被引用次数：20 · 研究领域：Hepatitis B Virus Studies、Hepatitis C virus research、Hepatitis Viruses Studies and Epidemiology

BACKGROUND: Treatment with bepirovirsen, an antisense oligonucleotide targeting hepatitis B virus (HBV) transcripts, has the potential to result in a functional cure, defined by at least 24 weeks of a sustained HBV DNA level below the lower limit of quantification (LLOQ) and hepatitis B surface antigen (HBsAg) loss after fixed-duration therapy. METHODS: In two replicate, double-blind trials (B-Well 1 and B-Well 2), we randomly assigned adults with noncirrhotic chronic HBV infection in a 2:1 ratio to receive subcutaneous bepirovirsen (at a weekly dose of 300 mg) or placebo for 24 weeks. All the patients were receiving stable nucleoside or nucleotide analogue (NA) therapy and had an HBsAg level of more than 100 to 3000 IU per milliliter. Eligible patients discontinued NA therapy at 48 weeks. The primary outcome was a functional cure at week 72. RESULTS: The percentage of patients with a functional cure at week 72 was significantly higher with bepirovirsen than with placebo both in the B-Well 1 trial (in 127 of 650 patients [20%] vs. none of 328 patients) and in the B-Well 2 trial (in 106 of 570 patients [19%] vs. none of 286 patients). In a pooled analysis at 72 weeks, adverse events were reported in 91% of the patients in the bepirovirsen groups and in 73% of those in the placebo groups; serious adverse events were reported in 7% and 4% of the patients, respectively. During the treatment period, adverse events of grade 3 or higher were reported in 16% of the patients who recei...