Henry L Y Chan1, Sang Hoon Ahn2, Ting-Tsung Chang3, Cheng-Yuan Peng4, David Wong5, Carla S Coffin6, Seng Gee Lim7, Pei-Jer Chen8, Harry L A Janssen9, Patrick Marcellin10, Lawrence Serfaty11, Stefan Zeuzem12, David Cohen13, Linda Critelli13, Dong Xu13, Megan Wind-Rotolo14, Elizabeth Cooney15. 1. The Chinese University of Hong Kong, Hong Kong SAR, China. 2. Yonsei University College of Medicine, Seoul, Republic of Korea. 3. National Cheng Kung University Hospital, Tainan, Taiwan. 4. China Medical University Hospital, Taichung, Taiwan. 5. Toronto Western Hospital University Health Network, Toronto, ON, Canada. 6. Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. 7. National University Hospital, Singapore. 8. National Taiwan University Hospital, Taipei, Taiwan. 9. Erasmus Medical Center, Rotterdam, Netherlands; University Health Network, Toronto, Canada. 10. Hôpital Beaujon and INSERM CRI Université Paris Diderot, Clichy, France. 11. Hôpital Saint Antoine, Paris, France. 12. Johann Wolfgang Goethe University, Frankfurt, Germany. 13. Bristol-Myers Squibb Research and Development, Wallingford, CT, USA. 14. Bristol-Myers Squibb Research and Development, Lawrenceville, NJ, USA. 15. Bristol-Myers Squibb Research and Development, Wallingford, CT, USA. Electronic address: elizabeth.cooney@bms.com.
Abstract
BACKGROUND & AIMS:Peginterferon lambda-1a (lambda) is a Type-III interferon, which, like alfa interferons, has antiviral activity in vitro against hepatitis B virus (HBV) and hepatitis C virus (HCV); however, lambda has a more limited extra-hepatic receptor distribution. This phase 2b study (LIRA-B) evaluated lambda in patients with chronic HBV infection. METHODS:Adult HBeAg+ interferon-naive patients were randomized (1:1) to weekly lambda (180 μg) or peginterferon alfa-2a (alfa) for 48 weeks. The primary efficacy endpoint was HBeAg seroconversion at week 24 post-treatment; lambda non-inferiority was demonstrated if the 80% confidence interval (80% CI) lower bound was >-15%. RESULTS: Baseline characteristics were balanced across groups (lambda N=80; alfa N=83). Early on-treatment declines in HBV-DNA and qHBsAg through week 24 were greater with lambda. HBeAg seroconversion rates were comparable for lambda and alfa at week 48 (17.5% vs. 16.9%, respectively); however lambda non-inferiority was not met at week 24 post-treatment (13.8% vs. 30.1%, respectively; lambda vs. alfa 80% CI lower bound -24%). Results for other key secondary endpoints (virologic, serologic, biochemical) and post hoc combined endpoints (HBV-DNA <2000 IU/ml plus HBeAg seroconversion or ALT normalization) mostly favored alfa. Overall adverse events (AE), serious AE, and AE-discontinuation rates were comparable between arms but AE-spectra differed (more cytopenias, flu-like, and musculoskeletal symptoms observed with alfa, more ALT flares and bilirubin elevations seen with lambda). Most on-treatment flares occurred early (weeks 4-12), associated with HBV-DNA decline; all post-treatment flares were preceded by HBV-DNA rise. CONCLUSIONS: On-treatment, lambda showed greater early effects on HBV-DNA and qHBsAg, and comparable serologic/virologic responses at end-of-treatment. However, post-treatment, alfa-associated HBeAg seroconversion rates were higher, and key secondary results mostly favored alfa. ClinicalTrials.gov number: NCT01204762.
RCT Entities:
BACKGROUND & AIMS: Peginterferon lambda-1a (lambda) is a Type-III interferon, which, like alfa interferons, has antiviral activity in vitro against hepatitis B virus (HBV) and hepatitis C virus (HCV); however, lambda has a more limited extra-hepatic receptor distribution. This phase 2b study (LIRA-B) evaluated lambda in patients with chronic HBV infection. METHODS: Adult HBeAg+ interferon-naive patients were randomized (1:1) to weekly lambda (180 μg) or peginterferon alfa-2a (alfa) for 48 weeks. The primary efficacy endpoint was HBeAg seroconversion at week 24 post-treatment; lambda non-inferiority was demonstrated if the 80% confidence interval (80% CI) lower bound was >-15%. RESULTS: Baseline characteristics were balanced across groups (lambda N=80; alfa N=83). Early on-treatment declines in HBV-DNA and qHBsAg through week 24 were greater with lambda. HBeAg seroconversion rates were comparable for lambda and alfa at week 48 (17.5% vs. 16.9%, respectively); however lambda non-inferiority was not met at week 24 post-treatment (13.8% vs. 30.1%, respectively; lambda vs. alfa 80% CI lower bound -24%). Results for other key secondary endpoints (virologic, serologic, biochemical) and post hoc combined endpoints (HBV-DNA <2000 IU/ml plus HBeAg seroconversion or ALT normalization) mostly favored alfa. Overall adverse events (AE), serious AE, and AE-discontinuation rates were comparable between arms but AE-spectra differed (more cytopenias, flu-like, and musculoskeletal symptoms observed with alfa, more ALT flares and bilirubin elevations seen with lambda). Most on-treatment flares occurred early (weeks 4-12), associated with HBV-DNA decline; all post-treatment flares were preceded by HBV-DNA rise. CONCLUSIONS: On-treatment, lambda showed greater early effects on HBV-DNA and qHBsAg, and comparable serologic/virologic responses at end-of-treatment. However, post-treatment, alfa-associated HBeAg seroconversion rates were higher, and key secondary results mostly favored alfa. ClinicalTrials.gov number: NCT01204762.
Authors: Thomas R O'Brien; Howard A Young; Raymond P Donnelly; Ludmila Prokunina-Olsson Journal: J Interferon Cytokine Res Date: 2019-04-17 Impact factor: 2.607
Authors: Marc G Ghany; Jordan J Feld; Kyong-Mi Chang; Henry L Y Chan; Anna S F Lok; Kumar Visvanathan; Harry L A Janssen Journal: Lancet Gastroenterol Hepatol Date: 2020-02-10
Authors: Juan L Mendoza; William M Schneider; Hans-Heinrich Hoffmann; Koen Vercauteren; Kevin M Jude; Anming Xiong; Ignacio Moraga; Tim M Horton; Jeffrey S Glenn; Ype P de Jong; Charles M Rice; K Christopher Garcia Journal: Immunity Date: 2017-03-21 Impact factor: 31.745