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.
Bibliographical noteFunding Information:
This study was sponsored by Bristol-Myers Squibb . The study was designed and conducted by the sponsor in collaboration with the principal investigators. The sponsor collected the data, monitored the study conduct, and performed the statistical analyses.
HLC: advisor and speaker for Bristol-Myers Squibb, Gilead, Roche, Novartis and MSD, a speaker for GlaxoSmithKline, Echosens and AbbVie, and has received an unrestricted grant for hepatitis B research from Roche; SHA: advisor and speaker for Bristol-Myers Squibb, Gilead, Roche, Novartis, MSD, Janssen, and AbbVie; and has received an unrestricted grant for hepatitis B research from Bristol-Myers Squibb, Gilead, and Roche; TTC: nothing to disclose; CYP; nothing to disclose; DW: nothing to disclose; CC: supported by the Canadian institutes of Health Research and has received speaker and advisory board fees and/or research support from Bristol-Myers Squibb, GlaxoSmithKline, Gilead, Janssen Pharmaceuticals, Boehringer Ingelheim, and Merck; SGL: advisory board fees from Gilead, Novartis, Merck Sharpe and Dohme, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, AbbVie, Vertex, Tobira, speakers’ bureau for Gilead, GlaxoSmithKline, Bristol-Myers Squibb, Novartis, Roche, and educational/research funding from Bristol-Myers Squibb, Novartis, Merck Sharpe and Dohme, and Gilead; PJC: personal fees and other from Bristol-Myers Squibb, grants from Roche and Janssen, and personal fees from Gilead; HLAJ: nothing to disclose; PM: grant, investigator, speaker, and expert for Roche, Gilead, Bristol-Myers Squibb, Novartis, Merck Sharpe and Dohme, and Janssen, investigator and expert for Vertex, and Abbott, grant and investigator for Alios BioPharma, and investigator for Pfizer, and Boehringer Ingelheim; LS: personal fees from Bristol-Myers Squibb, Janssen, Merck Sharpe and Dohme, Gilead, AbbVie, and Roche; SZ: consultancy for AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck, speakers’ bureau for AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck/Merck Sharpe and Dohme; DC, LC, DX, MWR, and EC are employees of Bristol-Myers Squibb.
This study was funded by Bristol-Myers Squibb. Editorial assistance was provided by Stephen Griffiths, PhD of Articulate Science Ltd. and was funded by Bristol-Myers Squibb.
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