Publication Date:
2026
Short description:
Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection / Hou, J., D., M., Lim, S., D., M., Buti, M., D., M., Yuen, M., Sc., D., Gane, E., D., M., Lampertico, P., D., M., H. D., P., Terrault, N., D., M., Nguyen, H., D., M., Joon Yim, H., D., M., H. D., P., et al.. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 1533-4406. - 394:24(2026). [10.1056/NEJMoa2515131]
abstract:
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.
Research Summary
Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection
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.
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.
Research Summary
Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection
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.
Iris type:
1.1 Articolo in rivista
List of contributors:
Hou, Jinlin; D., M.; Lim, Seng-Gee; D., M.; Buti, Maria; D., M.; Yuen, Man-Fung; Sc., D.; Gane, Edward; D., M.; Lampertico, Pietro; D., M.; H. D., P; Terrault, Norah; D., M.; Nguyen, Huy; D., M.; Joon Yim, Hyung; D., M.; H. D., P; Xie, Qing; D., M.; Lin, Jianmei; H. D., P; Qiu, Yunqing; D., M.; Jeng, Wen-Juei; D., M.; H. D., P; Heo, Jeong; D., M.; H. D., P; Peng, Cheng-Yuan; D., M.; H. D., P; Chen, Chien-Hung; D., M.; H. D., P; Chuang, Wan-Long; D., M.; Xie, Yao; D., M.; Hlebowicz, Maria; D., M.; H. D., P; Idriz, Nevin; D., M.; Mehta, Rajiv; D., M.; Agarwal, Kosh; D., M.; Gomes Da Silva, Monica M.; D., M.; H. D., P; Franca, Alex; D., M.; H. D., P; Cernat, Roxana; D., M.; H. D., P; Leerapun, Apinya; D., M.; Coffin, Carla S.; D., M.; Gadano, Adrian; D., M.; H. D., P; Andreone, Pietro; D., M.; Fujiyama, Shigetoshi; D., M.; H. D., P; Sevastianos, Vasileios; D., M.; H. D., P; Suzuki, Yuichiro; D., M.; H. D., P; Ratziu, Vlad; D., M.; Riachi, Ghassan; D., M.; Stocker, Hartmut; D., M.; Huey Lim, Tien; D., M.; Asselah, Tarik; D., M.; org/0000-0002-0024-0595, Ph. D. Https://orcid.; Tanaka, Yasuhito; D., M.; H. D., P; Holmes, Jacinta; B. B. S., M.; H. D., P; Liang, Xieer; D., M.; org/0000-0002-0862-3291, Ph. D. Https://orcid.; Cremer, Jennifer; M. D., Phar; Lukić, Tamara; D., M.; Plein, Helene; H. D., P; Quinn, Geoff; Sc., M.; Tao, Yu; H. D., P; Paff, Melanie; H. D., P; Theodore, Dickens; D., M.; Robert Elston, And; Raul Eduardo Adrover, Ph. D.; Margarita Anders, Maria; Oscar Bessone, Fernando; Carlos Gadano, Adrian; Alejandro Gaite, Luis; Mario Gruz, Fernando; Lacal Ridilenir, Veronica; Nuñez, Sebastian; Silva, Marcelo; George, Jacob; Holmes, Jacinta; Anne Leggett, Barbara; Sawhney, Rohit; Keith Henry Skoien, Richard; Roberto Brites Alves, Carlos; Silva Miranda Braga, Wornei; Reis Alvares Da Silva, Mario; Maria Da Silva, Monica; Vianey Calado Franca, Alex; Alexandre Kliemann, Dimas; Milton De Castro Lima, Jose; Madruga, Jose; Patelli Lima, Maria; Pessoa, Mario; Fernando Relvas, Luiz; Queiroz Reuter, Tania; Vargas Schwarzbold, Alexandre; Idriz, Nevin; Katzarov, Krum; Koleva, Yana; Kotzev, Iskren; Pavlov, Dimitar; Petrova, Diana; Sariyan, Simon; Tchernev, Konstantin; Chen, Tianyan; Coffin, Carla; L Cooper, Curtis; Doucette, Karen; Elkhashab, Magdy; Feld, Jordan; Ghesquiere, Wayne; Hercun, Julian; Klein, Marina; Ming Ma, Mang; Poulin, Sebastien; Ramji, Alnoor; T Szabo, Jason; Vachon, Marie-Louise; Wong, Alexander; Zhu, Julie; Chen, Chengwei; Chen, Liang; Dou, Xiaoguang; Du, Lingyao; Ge, Guohong; Guan, Yujuan; Han, Tao; Hou, Jinlin; Huang, Zuxiong; Jia, Jidong; Lin, Bingliang; Lu, Xiaobo; Luo, Yawen; Mao, Qianguo; Niu, Junqi; Qiu, Yunqing; Ren, Hong; Shang, Jia; Shaoli, You; Sheng, Guoping; Wei, Jia; Wu, Chao; Xie, Qing; Xie, Yao; Ye, Wei; Yongping, Yang; Yuan, Jing; Yuan, Shufang; Zhang, Jiming; Zhao, Yingren; Zheng, Xin; Abergel, Armando; Asselah, Tarik; De Ledinghen, Victor; Foucher, Juliette; Habersetzer, Francois; Noelle Hilleret, Marie; Jezequel, Caroline; Leroy, Vincent; Loustaud Ratti, Veronique; Mathurin, Philippe; Métivier, Sophie; Minello, Anne; Ratziu, Vlad; Riachi, Ghassan; Rosa, Isabelle; Silvain, Christine; Zoulim, Fabien; Bock, Hans; Grunwald, Stephan; Khaykin, Pavel; Lutz, Thomas; Potthoff, Anja; Sabranski, Michael; Seybold, Ulrich; Stocker, Hartmut; Wedemeyer, Heiner; Weinberg, Gordon; Cholongitas, Evangelos; Koutroubakis, Ioannis; Manolakopoulos, Spilios; Mimidis, Konstantinos; Sevastianos, Vasileios; Sinakos, Emmanouil; Triantos, Christos; Shiu Hong Chik, Thomas; Yin Owen Tsang, Tak; Lai Hung Wong, Grace; Fung Yuen, Man; Hajdú, Edit; Ilonczai, Péter; Makara, Mihaly; Martyin, Tibor; Muller, Zsofia; Pongor, Eva; Chaubal, Alisha; Chowdhury, Abhijit; Duseja, Ajay; P Gokak, Varadaraj; Goswami, Bhabadev; Habeeb, Aejaz; Hajare, Santosh; Ingle, Meghraj; Kalla, Mukesh; Kapoor, Dharmesh; Kumarasamy, Nagalingeshwaran; Lad, Saiprasad; Lawate, Parimal; Mandot, Ameetkumar; Mehta, Rajiv; G
Published in: