Dupilumab Efficacy in Children with Uncontrolled, Moderate-to-severe Type 2 Asthma, with and Without Evidence of Allergic Asthma in the VOYAGE Phase 3 Study

Background: Most pediatric asthma patients have type 2 asthma (baseline blood eosinophils ≥150 cells/µL or fractional exhaled nitric oxide [FeNO] ≥20 ppb), which includes the allergic phenotype. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4/IL-13, key and central drivers of type 2 inflammation in multiple diseases. In the 52-week, phase 3 VOYAGE study (NCT02948959), add-on dupilumab 100/200 mg (body weight ≤30 kg/>30 kg) every 2 weeks vs placebo reduced severe asthma exacerbations by 59.3% (P <0.0001) and improved pre-bronchodilator (BD) forced expiratory volume in 1 second percentage predicted (FEV1 pp) at Week (Wk) 12 (LS mean difference 5.2; P<0.001) in children aged 6 to <12 years with uncontrolled, moderate-to-severe type 2 asthma. We evaluated dupilumab efficacy in pediatric patients with type 2 asthma with/without evidence of an allergic asthma phenotype (serum total IgE ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35 kU/L at baseline).

Methods: Annualized severe asthma exacerbation rate (AER) was assessed in a post hoc analysis using a negative binomial model. Change from baseline in pre-BD FEV1 pp and Asthma Control Questionnaire (ACQ)-7-IA score were assessed using mixed-effect models with repeated measures.

Results: 350 pediatric patients with type 2 asthma were enrolled: 261 had evidence of an allergic phenotype; 89 did not. Baseline characteristics were similar between patients with/without evidence of an allergic phenotype; levels of type 2 biomarkers (blood eosinophils, FeNO, serum total IgE) and ongoing atopic comorbidities were higher in patients with evidence of an allergic phenotype. Dupilumab vs placebo significantly reduced AER in patients with/without evidence of an allergic phenotype (Table). Change from baseline in pre-BD FEV1 pp and ACQ-7 score was greater in patients treated with dupilumab vs placebo in both subgroups, and efficacy of dupilumab between subgroups was not statistically different (Table). In the overall safety population, TEAE incidence was similar across treatment groups; the most common TEAE occurring more frequently in the dupilumab group was injection-site erythema (12.9% dupilumab vs 9.7% placebo).

Conclusion: A high proportion (approximately 75%) of pediatric patients with type 2 asthma enrolled in VOYAGE had evidence of allergic asthma. In the subgroup of patients with evidence of allergic asthma, there were significant reductions in exacerbation rates and improvements in lung function and asthma control in dupilumab vs placebo. In the subgroup of patients with no evidence of allergic asthma, there was a significant reduction in exacerbation rates in patients receiving dupilumab vs placebo; mean numerical improvements were observed in lung function and asthma control.

Presenting Author(s)

NP
Nikolaos G. Papadopoulos, MD
Professor of Allergy
University of Athens
Athens, Attiki, Greece
Disclosure: AstraZeneca (Products/Services: speaker, advisory board member) (Speaker's Bureau, speaker, advisory board member)Boehringer Ingelheim (Products/Services: speaker, advisory board member) (Speaker's Bureau, speaker, advisory board member)GlaskoSmithKline (Products/Services: speaker, advisory board member) (Speaker's Bureau, speaker, advisory board member)HAL Allergy (Products/Services: speaker, advisory board member) (Speaker's Bureau, speaker, advisory board member)Menarini (Products/Services: speaker, advisory board member) (Speaker's Bureau, speaker, advisory board member)Mylan (Products/Services: speaker, advisory board member) (Speaker's Bureau, speaker, advisory board member)Novartis (Products/Services: speaker, advisory board member) (Speaker's Bureau, speaker, advisory board member)Nutricia (Products/Services: speaker, advisory board member) (Speaker's Bureau, speaker, advisory board member)OM Pharma (Products/Services: speaker, advisory board member) (Speaker's Bureau, speaker, advisory board member)Regeneron Pharmaceuticals, Inc. (Products/Services: speaker, advisory board member) (Speaker's Bureau, speaker, advisory board member)Sanofi (Products/Services: speaker, advisory board member) (Speaker's Bureau, speaker, advisory board member)

Co-Author(s)

Stanley J. Szefler, MD
Children’s Hospital Colorado
University of Colorado School of Medicine
University of Colorado School of Medicine
Aurora, Colorado
Disclosure: AstraZeneca (Products/Services: consultant fees paid to University) (Consultant)GlaskoSmithKline (Products/Services: consultant fees paid to University) (Consultant)Propeller Health (Products/Services: consultant fees paid to University) (Consultant)Regeneron Pharmaceuticals, Inc. (Products/Services: consultant fees paid to University) (Consultant)Sanofi (Products/Services: consultant fees paid to University) (Consultant)
LB
Leonard B. Bacharier, n/a
Professor of Pediatrics and Medicine
Monroe Carell Jr Children’s Hospital at Vanderbilt University Medical Center
Nashville, Tennessee
Disclosure: AstraZeneca (Products/Services: speaker fees) (Speaker's Bureau)Cystic Fibrosis Foundation (Products/Services: data and safety monitoring board) (Consultant)DBV Technologies (Products/Services: data and safety monitoring board) (Consultant)GlaskoSmithKline (Products/Services: speaker fees) (Speaker's Bureau)NIH (Products/Services: research support) (Grant/Research Support)Regeneron Pharmaceuticals, Inc. (Products/Services: speaker fees) (Speaker's Bureau)Sanofi (Products/Services: speaker fees, research support) (Grant/Research Support, Speaker's Bureau)Vectura (Products/Services: research support) (Grant/Research Support)
JM
Jorge F. Maspero, n/a
Professor
Fundación CIDEA
Buenos Aires, Buenos Aires, Argentina
Disclosure: AstraZeneca (Products/Services: consulting fees) (Consultant)GlaskoSmithKline (Products/Services: speaker fees) (Speaker's Bureau)Menarini (Products/Services: speaker fees) (Speaker's Bureau)Novartis (Products/Services: speaker fees; research grants) (Grant/Research Support, Speaker's Bureau)Sanofi (Products/Services: consulting fees) (Consultant)Uriach (Products/Services: speaker fees) (Speaker's Bureau)
CD
Christian Domingo, n/a
S.Pneumologia, planta primera, Edifici Tauli Nou
Corporació Sanitària Parc Taulí
Sabadell, Andalucia, Spain
Disclosure: ALK (Products/Services: travel and speaker fees) (Royalties)Allergy Therapeutics (Products/Services: travel and speaker fees) (Royalties)Almirall (Products/Services: travel and speaker fees) (Royalties)AstraZeneca (Products/Services: travel and speaker fees) (Royalties)Boehringer Ingelheim (Products/Services: travel and speaker fees) (Royalties)Chiesi (Products/Services: travel and speaker fees) (Royalties)Esteve (Products/Services: travel and speaker fees) (Royalties)Ferrer Pharma (Products/Services: travel and speaker fees) (Royalties)GlaskoSmithKline (Products/Services: travel and speaker fees) (Royalties)HAL Allergy (Products/Services: travel and speaker fees) (Royalties)Immunotek (Products/Services: travel and speaker fees) (Royalties)Menarini (Products/Services: travel and speaker fees) (Royalties)Novartis (Products/Services: travel and speaker fees) (Royalties)Pfizer (Products/Services: travel and speaker fees) (Royalties)Sanofi-Aventis (Products/Services: travel and speaker fees) (Royalties)Stallergenes Greer (Products/Services: travel and speaker fees) (Royalties)Takeda (Products/Services: travel and speaker fees) (Royalties)Teva (Products/Services: travel and speaker fees) (Royalties)
ND
Nadia Daizadeh, n/a
Former employee
Sanofi
Cambridge, Massachusetts
Disclosure: Sanofi (Products/Services: former employee) (Employee, Stockholder/Ownership Interest (excluding diversified mutual funds))
DL
David J. Lederer, MD
Medical Director, Clinical Sciences, Respiratory and Inflammation
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA
Tarrytown, New York
Disclosure: Regeneron Pharmaceuticals, Inc. (Products/Services: employees and shareholders) (Employee)
MH
Megan Hardin, n/a
Employee
Sanofi
Cambridge, Massachusetts
Disclosure: Sanofi (Products/Services: employee and shareholder) (Employee, Stockholder/Ownership Interest (excluding diversified mutual funds))
JJ
Juby A. Jacob-Nara, n/a
Employee
Sanofi
Bridgewater, New Jersey
Disclosure: Sanofi (Products/Services: employee, may hold stock and/or stock options in the company) (Employee, Stockholder/Ownership Interest (excluding diversified mutual funds))
YD
Yamo Deniz, n/a
Employee
Regeneron Pharmaceuticals, Inc.
Tarrytown, New York
Disclosure: Regeneron Pharmaceuticals, Inc. (Products/Services: employee and shareholder) (Employee, Stockholder/Ownership Interest (excluding diversified mutual funds))
RG
Rebecca Gall, n/a
Employee
Regeneron Pharmaceuticals, Inc.
Tarrytown, New York
Disclosure: Regeneron Pharmaceuticals, Inc. (Products/Services: employee and shareholder) (Employee, Stockholder/Ownership Interest (excluding diversified mutual funds))
BO
Benjamin Ortiz, n/a
Employee
Regeneron Pharmaceuticals, Inc.
Tarrytown, New York
Disclosure: Regeneron Pharmaceuticals, Inc. (Products/Services: employee and shareholder) (Employee, Stockholder/Ownership Interest (excluding diversified mutual funds))
MD
Michel Djandji, n/a
Employee
Sanofi
Cambridge, Massachusetts
Disclosure: Sanofi (Products/Services: employee, may hold stock and/or stock options in the company) (Employee, Stockholder/Ownership Interest (excluding diversified mutual funds))
PR
Paul J. Rowe, n/a
Employee
Sanofi
Bridgewater, New Jersey
Disclosure: Sanofi (Products/Services: employee, may hold stock and/or stock options in the company) (Employee, Stockholder/Ownership Interest (excluding diversified mutual funds))