Actividad Investigadora
Sequential Peg-IFN after bepirovirsen may reduce post-treatment relapse in chronic hepatitis B.
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Autores de IDIVAL
Autores ajenos al IDIVAL
- Buti M
- Heo J
- Tanaka Y
- Andreone P
- Atsukawa M
- Chak E
- Coffin CS
- Fujiwara K
- Gankina N
- Gordon SC
- Janczewska E
- Komori A
- Lampertico P
- McPherson S
- Morozov V
- Plesniak R
- Poulin S
- Ryan P
- Sagalova O
- Sheng G
- Voloshina N
- Xie Q
- Yim HJ
- Dixon S
- Paff M
- Felton L
- Lee M
- Greene T
- Lim J
- Lakshminarayanan D
- McGonagle G
- Plein H
- Youssef AS
- Elston R
- Kendrick S
- Theodore D
Unidades
Abstract
BACKGROUND & AIMS: 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-a-2a (Peg-IFN) therapy can reduce relapse and improve response rates. 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 <LLOQ for 24 weeks after planned end of Peg-IFN treatment, in the absence of newly initiated antiviral therapy. 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. FUNDING: GSK (study 209348/NCT04676724). CLINICAL TRIAL NUMBER: NCT04676724.
Copyright © 2024. Published by Elsevier B.V.
Datos de la publicación
- ISSN/ISSNe:
- 0168-8278, 1600-0641
- Tipo:
- Article
- Páginas:
- 222-234
- PubMed:
- 39214467
- Enlace a otro recurso:
- www.sciencedirect.com
- Factor de Impacto:
- 0,000 SCImago ℠
JOURNAL OF HEPATOLOGY ELSEVIER
Citas Recibidas en Web of Science: 40
Documentos
- No hay documentos
Filiaciones
Keywords
- Hepatitis B, antisense oligonucleotide, bepirovirsen, pegylated interferon-a-2a, sequential therapy
Campos de Estudio
Cita
Buti M, Heo J, Tanaka Y, Andreone P, Atsukawa M, Cabezas J, Chak E, Coffin CS, Fujiwara K, Gankina N, Gordon SC, Janczewska E, Komori A, Lampertico P, McPherson S, Morozov V, Plesniak R, Poulin S, Ryan P, Sagalova O, Sheng G, Voloshina N, Xie Q, Yim HJ, Dixon S, Paff M, Felton L, Lee M, Greene T, Lim J, Lakshminarayanan D, McGonagle G, Plein H, Youssef AS, Elston R, Kendrick S, Theodore D. Sequential Peg-IFN after bepirovirsen may reduce post-treatment relapse in chronic hepatitis B. J Hepatol. 2025. 82. (2):p. 222-234. IF:33,000. (1).
