A phase 3 trial evaluating the efficacy and safety of dupilumab (Dupixent®; Sanofi US and Regeneron), an interleukin-4 receptor alpha antagonist, in children with uncontrolled moderate to severe asthma met the primary and all key secondary end points.
The randomized, double-blind, placebo-controlled VOYAGE trial included 408 pediatric patients aged 6 to 11 years with uncontrolled persistent asthma. Patients were randomized to receive subcutaneous injections of dupilumab 100mg or 200mg every 2 weeks based on body weight or placebo, in addition to standard of care maintenance therapy (ie, medium dose inhaled corticosteroid [ICS] with a second controller medication or high dose ICS with or without a second controller medication).
The primary end point of the study was the annualized rate of severe asthma attacks in 2 specific populations: patients with baseline blood eosinophils (EOS) greater than or equal to 300 cells/μl and patients with markers of type 2 inflammation (fractional exhaled nitric oxide [FeNO] ≥20 ppb or EOS ≥150 cells/μl).
Results showed that over 52 weeks of treatment, dupilumab significantly reduced severe asthma attacks by 65% in patients with elevated baseline blood EOS (0.24 events/year; P <.0001) and by 59% in those with markers of type 2 inflammation (0.31 events/year; P <.0001) compared with placebo (0.67 and 0.75 events/year, respectively). Additionally, treatment with dupilumab was associated with significant improvement in lung function, which was observed as early as 2 weeks and was sustained for up to 52 weeks.
As for safety, the most commonly observed adverse events with dupilumab included injection site reactions, viral upper respiratory tract infections, and eosinophilia. The safety profile of dupilumab was found to be consistent with that observed in patients aged 12 years and older with moderate to severe asthma.
“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,” said John Reed, MD, PhD, Global Head of Research and Development at Sanofi. “These positive data are especially encouraging for younger children who are struggling to manage their uncontrolled asthma.”
The Companies expect to submit an application for regulatory approval for this indication in the first quarter of 2021.
Dupixent is currently approved as add-on maintenance treatment in patients 12 years of age and older with moderate to severe asthma with an eosinophilic phenotype or with oral corticosteroid dependent asthma.
It is also indicated for the treatment of moderate to severe atopic dermatitis in patients aged 12 years and older who are not adequately controlled with topical prescription therapies or when they are not advisable and as add-on maintenance treatment in adults with inadequately controlled chronic rhinosinusitis with nasal polyposis (CRSwNP).
Dupixent® (dupilumab) significantly reduced severe asthma attacks in children and is the only biologic to demonstrate improvement in children’s lung function in a randomized Phase 3 trial. [press release]. Tarrytown, NY: Sanofi; October 13, 2020.