Maria Buti, Jeong Heo, Yasuhito Tanaka, Pietro Andreone, Masanori Atsukawa, Joaquín Cabezas, Eric Chak, Carla S Coffin, Kei Fujiwara, Natalya Gankina, Stuart C Gordon, Ewa Janczewska, Atsumasa Komori, Pietro Lampertico, Stuart McPherson, Vyacheslav Morozov, Robert Plesniak, Sébastien Poulin, Pablo Ryan, Olga Sagalova, Guoping Sheng, Natalya Voloshina, Qing Xie, Hyung Joon Yim, Susan Dixon, Melanie Paff, Leigh Felton, Maximilian Lee, Thomas Greene, Jessica Lim, Divya Lakshminarayanan, Grant McGonagle, Helene Plein, Amir Youssef, Rob Elston, Stuart Kendrick, Dickens Theodore
{"title":"贝匹韦森治疗后序贯 Peg-IFN 可减少慢性乙型肝炎的治疗后复发。","authors":"Maria Buti, Jeong Heo, Yasuhito Tanaka, Pietro Andreone, Masanori Atsukawa, Joaquín Cabezas, Eric Chak, Carla S Coffin, Kei Fujiwara, Natalya Gankina, Stuart C Gordon, Ewa Janczewska, Atsumasa Komori, Pietro Lampertico, Stuart McPherson, Vyacheslav Morozov, Robert Plesniak, Sébastien Poulin, Pablo Ryan, Olga Sagalova, Guoping Sheng, Natalya Voloshina, Qing Xie, Hyung Joon Yim, Susan Dixon, Melanie Paff, Leigh Felton, Maximilian Lee, Thomas Greene, Jessica Lim, Divya Lakshminarayanan, Grant McGonagle, Helene Plein, Amir Youssef, Rob Elston, Stuart Kendrick, Dickens Theodore","doi":"10.1016/j.jhep.2024.08.010","DOIUrl":null,"url":null,"abstract":"<p><strong>Background & aims: </strong>Bepirovirsen, an antisense oligonucleotide, induces sustained hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA below lower limit of quantification (<LLOQ) in a subset of patients. The B-Together study investigated if sequential bepirovirsen and pegylated interferon-α-2a (Peg-IFN) therapy can reduce relapse and improve response rates.</p><p><strong>Methods: </strong>Phase 2b, multicentre, randomised, open-label trial. Participants on stable nucleos(t)ide analog (NA) therapy were randomised 1:1 to bepirovirsen 300 mg once weekly (plus loading dose on Days 4 and 11) for 24 (Arm 1) or 12 (Arm 2) weeks followed by Peg-IFN 180 mcg once weekly for up to 24 weeks, with up to 36 weeks follow-up. Participants continued NA therapy throughout.</p><p><strong>Primary outcome: </strong>proportion of participants with HBsAg <0.05 IU/mL and HBV DNA <LLOQ for 24 weeks after planned end of Peg-IFN treatment, in the absence of newly initiated antiviral therapy.</p><p><strong>Results: </strong>The intent-to-treat population included 108 participants (Arm 1=55; Arm 2=53). The primary outcome was achieved by 5 (9%) participants in Arm 1 and 8 (15%) in Arm 2. All responders had baseline HBsAg ≤3000 IU/mL. Indirect comparison with the Phase 2b study B-Clear indicates that sequential addition of Peg-IFN may reduce the relapse rates previously observed with bepirovirsen alone. The proportions of participants with adverse events (AEs) and treatment-related AEs in both treatment windows were similar between treatment arms.</p><p><strong>Conclusions: </strong>Sequential therapy with bepirovirsen followed by Peg-IFN is tolerable and effective in participants with chronic HBV infection on stable NA. This proof-of-concept trial demonstrates a potential strategy to extend responses to bepirovirsen by reducing relapse.</p><p><strong>Funding: </strong>GSK (study 209348/NCT04676724).</p><p><strong>Clinical trial number: </strong>NCT04676724.</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8000,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sequential Peg-IFN after bepirovirsen may reduce post-treatment relapse in chronic hepatitis B.\",\"authors\":\"Maria Buti, Jeong Heo, Yasuhito Tanaka, Pietro Andreone, Masanori Atsukawa, Joaquín Cabezas, Eric Chak, Carla S Coffin, Kei Fujiwara, Natalya Gankina, Stuart C Gordon, Ewa Janczewska, Atsumasa Komori, Pietro Lampertico, Stuart McPherson, Vyacheslav Morozov, Robert Plesniak, Sébastien Poulin, Pablo Ryan, Olga Sagalova, Guoping Sheng, Natalya Voloshina, Qing Xie, Hyung Joon Yim, Susan Dixon, Melanie Paff, Leigh Felton, Maximilian Lee, Thomas Greene, Jessica Lim, Divya Lakshminarayanan, Grant McGonagle, Helene Plein, Amir Youssef, Rob Elston, Stuart Kendrick, Dickens Theodore\",\"doi\":\"10.1016/j.jhep.2024.08.010\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background & aims: </strong>Bepirovirsen, an antisense oligonucleotide, induces sustained hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA below lower limit of quantification (<LLOQ) in a subset of patients. The B-Together study investigated if sequential bepirovirsen and pegylated interferon-α-2a (Peg-IFN) therapy can reduce relapse and improve response rates.</p><p><strong>Methods: </strong>Phase 2b, multicentre, randomised, open-label trial. Participants on stable nucleos(t)ide analog (NA) therapy were randomised 1:1 to bepirovirsen 300 mg once weekly (plus loading dose on Days 4 and 11) for 24 (Arm 1) or 12 (Arm 2) weeks followed by Peg-IFN 180 mcg once weekly for up to 24 weeks, with up to 36 weeks follow-up. Participants continued NA therapy throughout.</p><p><strong>Primary outcome: </strong>proportion of participants with HBsAg <0.05 IU/mL and HBV DNA <LLOQ for 24 weeks after planned end of Peg-IFN treatment, in the absence of newly initiated antiviral therapy.</p><p><strong>Results: </strong>The intent-to-treat population included 108 participants (Arm 1=55; Arm 2=53). The primary outcome was achieved by 5 (9%) participants in Arm 1 and 8 (15%) in Arm 2. All responders had baseline HBsAg ≤3000 IU/mL. Indirect comparison with the Phase 2b study B-Clear indicates that sequential addition of Peg-IFN may reduce the relapse rates previously observed with bepirovirsen alone. The proportions of participants with adverse events (AEs) and treatment-related AEs in both treatment windows were similar between treatment arms.</p><p><strong>Conclusions: </strong>Sequential therapy with bepirovirsen followed by Peg-IFN is tolerable and effective in participants with chronic HBV infection on stable NA. This proof-of-concept trial demonstrates a potential strategy to extend responses to bepirovirsen by reducing relapse.</p><p><strong>Funding: </strong>GSK (study 209348/NCT04676724).</p><p><strong>Clinical trial number: </strong>NCT04676724.</p>\",\"PeriodicalId\":15888,\"journal\":{\"name\":\"Journal of Hepatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":26.8000,\"publicationDate\":\"2024-08-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Hepatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jhep.2024.08.010\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Hepatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jhep.2024.08.010","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Sequential Peg-IFN after bepirovirsen may reduce post-treatment relapse in chronic hepatitis B.
Background & aims: Bepirovirsen, an antisense oligonucleotide, induces sustained hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA below lower limit of quantification (
Methods: Phase 2b, multicentre, randomised, open-label trial. Participants on stable nucleos(t)ide analog (NA) therapy were randomised 1:1 to bepirovirsen 300 mg once weekly (plus loading dose on Days 4 and 11) for 24 (Arm 1) or 12 (Arm 2) weeks followed by Peg-IFN 180 mcg once weekly for up to 24 weeks, with up to 36 weeks follow-up. Participants continued NA therapy throughout.
Primary outcome: proportion of participants with HBsAg <0.05 IU/mL and HBV DNA
Results: The intent-to-treat population included 108 participants (Arm 1=55; Arm 2=53). The primary outcome was achieved by 5 (9%) participants in Arm 1 and 8 (15%) in Arm 2. All responders had baseline HBsAg ≤3000 IU/mL. Indirect comparison with the Phase 2b study B-Clear indicates that sequential addition of Peg-IFN may reduce the relapse rates previously observed with bepirovirsen alone. The proportions of participants with adverse events (AEs) and treatment-related AEs in both treatment windows were similar between treatment arms.
Conclusions: Sequential therapy with bepirovirsen followed by Peg-IFN is tolerable and effective in participants with chronic HBV infection on stable NA. This proof-of-concept trial demonstrates a potential strategy to extend responses to bepirovirsen by reducing relapse.
期刊介绍：
The Journal of Hepatology is the official publication of the European Association for the Study of the Liver (EASL). It is dedicated to presenting clinical and basic research in the field of hepatology through original papers, reviews, case reports, and letters to the Editor. The Journal is published in English and may consider supplements that pass an editorial review.
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