Study Provides More Positive Dupilumab Data for Children With Moderate to Severe Asthma

Additional evidence was released Wednesday about the effects of dupilumab in reducing the rate of severe asthma attacks and improving lung function and asthma control in children aged 6 to 11 years; the biologic targeting type 2 inflammation was approved for these pediatric patients in October.

The results were published in The New England Journal of Medicine.

The data came from the pivotal phase 3, multinational, randomized, double-blind, placebo-controlled Liberty Asthma VOYAGE (Evaluation of Dupilumab in Children with Uncontrolled Asthma) trial to assess the efficacy and safety of the drug in children with moderate to severe asthma.

Current guidelines recommend using an elevated peripheral-blood eosinophil count (≥150 cells/mm³) or an elevated fraction of exhaled nitric oxide (FeNO ≥20 parts per billion), or both, as cutoff values when trying to identify patients who may improve on biologics that target type 2 inflammation.

Most of the 408 participants had type 2 inflammation; the enrollment of patients with a baseline blood eosinophil count below 150 cells/mm³ was capped at 20%. In addition, eligibility required at least 1 severe exacerbation in the past year, a 3-month history of receiving either a medium-dose inhaled glucocorticoid in combination with a second controller or a high-dose inhaled glucocorticoid alone or in combination with a second controller at a stable dose for at least 1 month before screening, a prebronchodilator forced expiratory volume in 1 second (FEV₁) of 95% or less of the predicted value at screening and baseline visits, and FEV₁ reversibility of 10% or more.

Investigators assigned the children to receive a subcutaneous injection of dupilumab (at a dose of 100 mg for those weighing ≤30 kg and 200 mg for those weighing >30 kg) or matched placebo every 2 weeks for 52 weeks. For both groups, their regular asthma therapy continued.

Results demonstrated:

• The annualized rate of severe asthma exacerbations was 0.31 (95% CI, 0.22-0.42) with dupilumab compared with 0.75 (95% CI, 0.54-1.03) in the placebo group
• The relative risk reduction in patients receiving dupilumab was 59.3% (95% CI, 39.5%-72.6%; P <.001).
• The mean (SE) change from baseline in FEV₁ was 10.5 (1.0) percentage points with dupilumab and 5.3 (1.4) percentage points with placebo (mean difference, 5.2 percentage points; 95% CI, 2.18.3; P <.001).

Dupilumab also resulted in significantly better asthma control than placebo (P <.001). Similar results were observed in the patients with an eosinophil count of at least 300 cells/mm³ at baseline.

In addition, more patients with type 2 inflammation receiving dupilumab had no exacerbations (77.1%) compared with 59.6% on placebo. Results were similar for those with at least 300 eosinophils per cubic millimeter at baseline.

Children receiving dupilumab also had a lower risk of loss of asthma control and received fewer treatment courses with systemic glucocorticoids.

The incidence of serious adverse events was similar in the 2 groups; parasitic infections were reported in 7 patients (2.6%) in the dupilumab group. Investigators did not consider the infections to be related to the study drug.

In a statement, the international lead investigator for the trial said the next frontier for dupilumab is likely to involve using it even earlier than age 6.

“Can we use this agent earlier in life to change how the disease develops? I think that’s the next frontier,” said Leonard Bacharier, MD, an asthma specialist at Monroe Carell Jr. Children’s Hospital at Vanderbilt University.

In addition, patients in the trial were invited to join an extension trial for another year, with all participants receiving dupilumab. The extension trial will focus on both efficacy and long-term safety; results should be available mid-2022.

The study had some limitations, including a lack of diversity, the investigators noted. Although participant makeup reflected the demographics of the 99 trial sites, the low number of enrolled Black children “should be considered when generalizing findings to the wider population of children with asthma. The inclusion of these underrepresented populations in future studies is needed,” the authors wrote.

In addition, the “rapid decrease in the FeNO among the children receiving dupilumab could have given investigators a suspicion of trial-group assignment that could have had an effect on treatment decisions,” they said, although the findings about the effect of the biologic on FeNO in older populations was not known at the start of this trial.

Dupilumab is also approved for atopic dermatitis and chronic rhinosinusitis with nasal polyposis. The study was funded by the drugmakers.

Reference

Bacharier LB, Maspero JF, Katelaris CH, et al. Dupilumab in children with uncontrolled moderate-to-severe asthma. N Engl J Med. 2021;385:2230-224. doi:10.1056/NEJMoa2106567