Assessment of long-term safety and efficacy of dupilumab in children with asthma (LIBERTY ASTHMA EXCURSION): an open-label extension study.

Background: Dupilumab efficacy and safety in children aged 6-11 years with uncontrolled, moderate-to-severe asthma were shown in the VOYAGE study-a 52-week, multinational, multicentre, phase 3 randomised, double-blind, placebo-controlled trial. We aimed to evaluate the long-term safety and efficacy of dupilumab in children with moderate-to-severe asthma who previously participated in the VOYAGE study.
Methods: 365 of 408 children with moderate-to-severe asthma from VOYAGE enrolled in EXCURSION, a 52 week, open-label extension study conducted at 70 centres across 17 countries. 240 children continued with add-on dupilumab (dosed according to bodyweight: 100 mg for those weighing ≤30 kg and 200 mg for those weighing more than 30 kg at EXCURSION baseline) once every 2 weeks administered by subcutaneous injection (dupilumab/dupilumab group) and 125 children on placebo during VOYAGE initiated dupilumab (100 or 200 mg, according to bodyweight), once every 2 weeks administered by subcutaneous injection (placebo/dupilumab group). Following a protocol amendment, for a subset of children weighing 30 kg or less, the dose was changed to 300 mg once every 4 weeks. The primary endpoint for the open-label extension study was the number and proportion of patients with any treatment-emergent adverse event (TEAE) during the 52-week study period in the overall population (defined as children aged 6-11 years old with moderate-to-severe asthma who previously completed VOYAGE). Statistical analyses were descriptive. This study is registered with ClinicalTrials.gov (NCT03560466; EXCURSION).
Findings: Children who completed VOYAGE were eligible to enrol in EXCURSION between June 21, 2018 and Aug 18, 2020. During EXCURSION, the safety profile and proportion of patients reporting TEAEs were consistent with those observed during the parent study (VOYAGE). In the overall population, 232 (63·6%) of 365 patients experienced at least one TEAE (dupilumab/dupilumab: 147 [61·3%]; placebo/dupilumab: 85 [68·0%]). The most frequently reported TEAEs were nasopharyngitis, pharyngitis, and upper respiratory tract infections.
Interpretation: In EXCURSION, long-term treatment with dupilumab was well tolerated with an acceptable safety profile.
Funding: Sanofi and Regeneron Pharmaceuticals.
Competing Interests: Declaration of interests LBB has received speaker fees from AstraZeneca, GSK, Regeneron Pharmaceuticals, and Sanofi; is a member of the data and safety monitoring board for DBV Technologies and Cystic Fibrosis Foundation; and has received research support from the US National Institutes of Health, Sanofi, and Vectura. JFM is a consultant for AstraZeneca and Sanofi; has received speaker fees from GSK, Menarini, Novartis, and Uriach; and reports research grants from Novartis. CHK reports honoraria for presentations; and was a principal investigator of the dupilumab asthma phase 2b (NCT01854047) and phase 3 (NCT02414854) studies for Regeneron Pharmaceuticals and Sanofi. AGF is a member of the advisory boards for Abbott, Danone, DBV Technologies, HiPP Organic, Novartis, and Stallergenes Greer; and reports currently sponsoring research from Danone, Ferrero, HiPP Organic, and Sanofi. RG reports research grants from ALK, AstraZeneca, BioCryst, DBV Technologies, Genentech, Greencross, Novartis, Regeneron Pharmaceuticals, Sanofi, and Shire; is a consultant for ALK, AstraZeneca, Pfizer, and Sanofi; and has received speaker fees from Novartis. IdM reports personal fees for lectures and boards from GSK and Sanofi; conference registration and travel fees from Novartis; and conference registration fees from Aldo-Unión. TWG reports grants from NIH and GSK; grants and consulting fees from Sanofi, Regeneron Pharmaceuticals, Amgen, and AstraZeneca; consulting fees from Novartis, Genentech, Polarean, OM Pharma, AiCME, and Best Pharmaceuticals for Children Act; and royalties from UpToDate. DJJ is a consultant for AstraZeneca, Avillion, GSK, Novartis, Regeneron Pharmaceuticals, Sanofi, and Vifor Pharma; and is a member of the data and safety monitoring board for Pfizer. HWS, NL, EL, LPM, KT, MH, RMA, and LBR are employees of Sanofi, and might hold stock or stock options in the company. BA, JM, FAK, and DJL are employees and shareholders of Regeneron Pharmaceuticals.
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