Year: 2026
Type: article
Study design: Clinical Trial
Abstract: 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 received bepirovirsen and in 3% of those who received placebo; increases in the alanine aminotransferase level were the most common grade 3 adverse events with bepirovirsen (in 6% of the patients). CONCLUSIONS: In two phase 3 trials involving patients with chronic HBV infection, a functional cure after the discontinuation of NA therapy was reported in significantly more patients treated with bepirovirsen than in those who received placebo. (Funded by GSK; ClinicalTrials.gov numbers, NCT05630807 and NCT05630820.).
Source: New England Journal of Medicine
Authors: Jinlin Hou, Seng-Gee Lim, Maria Buti, Man-Fung Yuen, Edward Gane, Pietro Lampertico, Norah Terrault, Huy Nguyen, Hyung Joon Yim, Qing Xie, Jianmei Lin, Yunqing Qiu, Wen-Juei Jeng, Jeong Heo, Cheng-Yuan Peng, Chien-Hung Chen, Wan-Long Chuang, Yao Xie, Maria Hlebowicz, Nevin Idriz, Rajiv Mehta, Kosh Agarwal, Monica M. Gomes da 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
Institutions: Nanfang Hospital, Southern Medical University, National University Health System, Vall d'Hebron Hospital Universitari, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Queen Mary Hospital, University of Hong Kong, University of Auckland, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Southern California, Korea University Ansan Hospital, Shanghai Jiao Tong University, Ruijin Hospital, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, First Affiliated Hospital Zhejiang University, Chang Gung University, Chang Gung Memorial Hospital, Linkou Chang Gung Memorial Hospital, Pusan National University Hospital, Pusan National University, China Medical University, China Medical University Hospital, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung Medical University, Kaohsiung Medical University Chung-Ho Memorial Hospital, Beijing Ditan Hospital, University of Warmia and Mazury in Olsztyn, Medical University of Sofia, Sids Hospital and Research Center, King's College Hospital, Hospital de Clínicas Universidade Federal do Paraná, Universidade Federal do Paraná, Universidade Federal de Sergipe, Ovidius University, Chiang Mai University, University of Calgary, Hospital Italiano de Buenos Aires, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Kumamoto Shinto General Hospital, Evangelismos Hospital, University of Yamanashi, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Hôpital Charles-Nicolle, Centre Hospitalier Universitaire de Rouen, St. Joseph-Krankenhaus, Inserm, Université Paris Cité, Hôpital Beaujon, Kumamoto University, The University of Melbourne, St Vincent's Hospital Melbourne, GlaxoSmithKline (United Kingdom), GlaxoSmithKline (United States)
Language: English
Topic: Hepatitis B Virus Studies
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: GlaxoSmithKline
Awards: G6303004170, G7309957590
OpenAlex ID: W7162665130