Improvements in lung function occurred as early as 2 weeks after the first dose of treatment.
A pivotal phase 3 trial found that dupilumab (Dupixent) significantly reduced severe asthma attacks over 1 year compared with placebo in children aged 6 to 11 years with moderate to severe asthma. Lung improvements were seen as early as 2 weeks after the first dose, according to Sanofi and Regeneron, which are jointly developing the drug.
Dupilumab is a fully human monoclonal antibody that inhibits interleukin (IL)-4 and IL-13, which are key drivers of the type 2 inflammation that plays a major role in asthma, chronic rhinosinusitis with nasal polyps, atopic dermatitis, and eosinophilic esophagitis.
“Children with uncontrolled moderate-to-severe asthma often struggle to breathe, largely because of their impaired lung function, and this can have a serious impact on their quality of life,” John Reed, MD, PhD, global head of research and development at Sanofi, said in a statement. “Dupixent is the only biologic shown in a controlled phase 3 trial to improve lung function in children, which is generally consistent with results seen in the adolescent and adult trials.”
The LIBERTY ASTHMA VOYAGE trial is a phase 3, randomized double-blind, placebo-controlled study of 408 children. The study assessed the annualized rate of severe asthma attacks in patients with baseline blood eosinophils (EOS) of at least 300 cells/mcL and in patients with markers of type 2 inflammation (fractional exhaled nitric oxide ≥ 20 ppb or EOS ≥ 150 cells/mcL).
Patients received either subcutaneous dupilumab 100 mg or 200 mg (based on weight) every 2 weeks to standard of care or placebo. There was a 65% average reduction in rate of asthma attacks over 1 year for patients on dupilumab 100 mg and a 59% reduction for patients on dupilumab 200 mg.
At 12 weeks, compared with baseline, patients had improved lung function by 10.15 percentage points on dupilumab 100 mg and by 10.53 percentage points for dupilumab 200 mg vs 4.83 and 5.32 percentage points for placebo (least squares mean difference for dupilumab vs placebo of 5.3 and 5.2 percentage points, P = .0036 and P = .0009). Improved lung function was measured for percent predicted forced expiratory volume in 1 second (FEV1pp). The improvement began as early as 2 weeks after treatment and was sustained for up to 52 weeks.
FEV1pp is commonly used in pediatric asthma trials because it accounts for children’s growing lung capacity at different stages of development by evaluating a patient’s change in lung function compared with their predicted lung function based on a number of factors including age, height, and sex.
The safety results of the trial were consistent with the known safety profile of the therapy in this patient population. The most commonly observed adverse events with dupilumab vs placebo were injection site reactions (18% vs 13%), viral upper respiratory tract infections (12% vs 10%), and eosinophilia (6% vs 1%).
“Children with moderate-to-severe asthma live with a heavy and unpredictable disease burden. Even while taking maximum treatments including inhaled corticosteroids, they suffer from multiple asthma attacks each year that may require hospitalization,” said George D. Yancopoulos, MD, PhD, president and chief scientific officer of Regeneron. “These impressive Phase 3 data in children with asthma show Dupixent significantly reduced annual severe asthma attacks and also improved lung function consistently across patients with markers of type 2 inflammation.”
Sanofi and Regeneron are planning US and EU regulatory submissions for the use of dupilumab to treat asthma in children aged 6 to 11 years by the end of the first quarter of 2021.