538 - Efficacy of Dupilumab in Quadrants of Elevated vs Low Type 2 Biomarkers in Children With Uncontrolled, Moderate-to-Severe Asthma: LIBERTY ASTHMA VOYAGE

Poster Number: 538
Publication Number: 538.242

Leonard B. Bacharier, Monroe Carell Jr Children’s Hospital at Vanderbilt University Medical Center, Nashville, TN, United States; Daniel J. jackson, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; Ian D. Pavord, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK, Oxford, England, United Kingdom; jorge f. maspero, Fundacion Cidea, Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina; Xuezhou Mao, Sanofi, Bridgewater, NJ, United States; Dongfang Liu, Sanofi, Beijing, Beijing, China (People's Republic); Juby A. Jacob-Nara, Sanofi, Bridgewater, NJ, United States; Yamo Deniz, Regeneron, Tarrytown, NY, United States; Elizabeth Laws, Sanofi, Bridgewater, NJ, United States; Leda Mannent, sanofi, Chilly Mazarin, Ile-de-France, France; Nikhil Amin, Regeneron, Chappaqua, NY, United States; Bolanle Akinlade, Regeneron Pharmaceuticals, Tarrytown, NY, United States; David J. Lederer, Regeneron Pharmaceuticals, Tarrytown, NY, United States; Megan Hardin, Sanofi Genzyme, Cambridge, MA, United States

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation in multiple diseases. In the phase 3 VOYAGE study (NCT02948959), dupilumab 100/200 mg vs placebo every 2 weeks for 52 weeks reduced severe asthma annualized exacerbation rate (AER) and improved pre-bronchodilator percent predicted forced expiratory volume in 1 second (ppFEV1) in children aged 6–11 years with uncontrolled, moderate-to-severe asthma.

Objective: We evaluated the predictive value of baseline blood eosinophil and fractional exhaled nitric oxide (FeNO) levels as biomarkers for dupilumab response.

Design/Methods: The population was clustered into quadrants based on baseline blood eosinophil (< vs ≥ 150 cells/µL) and FeNO levels (< vs ≥ 20 parts per billion). The relative risk (RR) for AER and change from baseline in ppFEV1 at Week 12 were evaluated.

Results: AER was reduced in the high eosinophils/low FeNO (n = 137, RR 0.473; 95% CI 0.26, 0.85) and high eosinophils/high FeNO (n = 184, RR 0.351; 95% CI 0.20, 0.61) quadrants, and was numerically lower in the high FeNO/low eosinophils (n = 19, RR 0.449; 95% CI 0.05, 3.99) quadrant, but not in the low eosinophils/low FeNO (n = 56, RR 1.295; 95% CI 0.36, 4.69) quadrant. Values for ppFEV1 were numerically higher in dupilumab- vs placebo-treated patients at Week 12 in all quadrants: high eosinophils/low FeNO (least squares [LS] mean difference 2.90; 95% CI −1.51, 7.31), high eosinophils/high FeNO (LS mean difference 6.44; 95% CI 2.01, 10.87), high FeNO/low eosinophils (LS mean difference 3.61; 95% CI −22.71, 29.92), low eosinophils/low FeNO (LS mean difference 1.38; 95% CI −6.13, 8.90).Conclusion(s): Dupilumab reduced exacerbations and led to numerical improvements in lung function among children with elevated blood eosinophils and/or FeNO.