P4A052: Long-term Safety and Sustained Efficacy of Dupilumab Treatment in Children with Moderate-to-severe Asthma: LIBERTY ASTHMA EXCURSION

Background: Asthma is one of the most common chronic childhood diseases, mainly driven by type 2 inflammation. There is an unmet need for treatment options that provide long-term improvement of lung function and exacerbation reduction in type 2 asthma patients. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins (IL) 4 and IL-13, key and central drivers of type 2 inflammation. The phase 3 VOYAGE study (NCT02948959) demonstrated the efficacy and safety of dupilumab in children aged 6 to 11 years with uncontrolled, moderate-to-severe asthma for up to 52 weeks. This analysis presents data from the phase 3 EXCURSION single-arm, open-label, extension study (NCT03560466), assessing the long-term safety and efficacy of dupilumab in children who completed VOYAGE.

Methods: 365 of 408 children from VOYAGE enrolled in EXCURSION. These patients received add-on dupilumab 100 or 200 mg every 2 weeks or 300 mg every 4 weeks (based on body weight) for 52 weeks. We assessed treatment-emergent adverse events (TEAE) in all patients. In the type 2 asthma population (blood eosinophils ≥ 150 cells/L, or fractional exhaled nitric oxide [FeNO] ≥ 20 ppb at parent study baseline [PSBL]) endpoints assessed were annualized severe exacerbation rates (AER), changes from PSBL in pre-bronchodilator percent predicted (pp) FEV1 and pre-bronchodilator FEV1 z-score over time.

Results: Safety during EXCURSION was consistent with that seen in the the parent study . Reductions in AER and pre-bronchodilator ppFEV1 improvements in response to dupilumab that were observed in VOYAGE were maintained throughout EXCURSION. (Table). In the type 2 asthma population, pre-bronchodilator ppFEV1 z-scores at PSBL (mean [SD]) were −1.84 (1.20) in the dupilumab/dupilumab group and −1.70 (1.18) in the placebo/dupilumab group. At Week 12 of EXCURSION this had improved to -0.68 (1.33) in the dupilumab/dupilumab group and -0.75 (1.32) in the placebo/dupilumab group, and at Week 52 of EXCURSION they were 0.22 (1.51) in the dupilumab/dupilumab group and 0.08 (1.59) in the placebo/dupilumab group. By Week 52, 92.4% of children achieved normal lung function (z-score > lower limit of normal, −1.64) in the dupilumab/dupilumab group, and 93.9% in the placebo/dupilumab group.

Conclusion: Long-term use of dupilumab was well tolerated in pediatric patients with asthma. Efficacy of dupilumab observed in VOYAGE in the type 2 asthma population was sustained in EXCURSION over 52 weeks, with rapid lung function improvement in patients initiating dupilumab.