Data Show Dupilumab Significantly Reduces Asthma Attacks, Improves Lung Function in Children
Patients who added dupilumab to standard of care saw a 65% reduction in the rate of severe asthma attacks over 1 year.
New data from a randomized phase 3 trial indicate that dupilumab (Dupixent) is effective in reducing pediatric asthma attacks and improving lung function. An FDA decision for children with moderate-to-severe asthma is expected by October 21, 2021.
Asthma is the most common chronic disease in children, with approximately 75,000 children between 6 and 11 years of age living with uncontrolled moderate-to-severe asthma in the United States. Although many receive treatment with standard-of-care inhaler corticosteroids and bronchodilators, many children continue to experience serious symptoms such as coughing, wheezing, and difficulty breathing.
Managing asthma can also require multiple courses of systemic corticosteroids that carry significant risks. Children who have asthma and underlying type 2 inflammation are more likely to have poor disease control, more frequent asthma attacks, and symptoms that interfere with their day-to-day activities.
“Children living with uncontrolled moderate-to-severe asthma experience serious and persistent symptoms that can impact many crucial aspects of their lives including school, sleep, and exercise,” said Leonard B. Bacharier, MD, director of the Center for Pediatric Asthma Research, in the press release.
Dupilumab is a fully human monoclonal antibody that inhibits signaling of the interleukin-4 and interleukin-13 pathways. Both of these pathways are central drivers of the type 2 inflammation that plays a major role in asthma, chronic rhinosinusitis with nasal polyposis, atopic dermatitis, and eosinophilic esophagitis.
The VOYAGE trial investigated the use of dupilumab in children aged 6 to 11 years with uncontrolled moderate-to-severe asthma, with evidence of type 2 inflammation. They found that it rapidly improved lung function and significantly improved overall asthma symptom control. Furthermore, dupixent reduced fractional exhaled nitric oxide (FeNO), an airway biomarker of type 2 inflammation that plays a major role in asthma.
The 408 trial participants received 100 mg or 200 mg of dupixent every 2 weeks, based on weight, combined with standard-of-care therapy. Two pre-specified subgroups with evidence of type 2 inflammation were evaluated for the primary analysis: patients with baseline blood eosinophils ≥300 cells/μl and patients with FeNO ≥20 parts per billion or EOS ≥150 cells/μl; n=350. The trial met its primary and key secondary endpoints.
In the 2 subgroups, patients who added dupilumab to standard of care saw a 65% reduction in the rate of severe asthma attacks over 1 year, compared to a 59% reduction in the placebo group. Similarly, participants in the dupilumab arm experienced improved lung function as early as 2 weeks and sustained for up to 52 weeks, as measured by percent predicted FEV1.
In the primary patient population, patients experienced significant improvements in asthma control. On a 0 to 6 scale, patients taking dupilumab improved their asthma control scores by 1.34 for symptoms and 1.33 for impact at week 24, compared to 0.88 and 1.00, respectively, for the placebo group. Notably, the improvement from baseline in patients taking dupilumab was more than double the clinically meaningful threshold of 0.5 points on the Asthma Control Questionnaire 7-Interviewer Administered.
Researchers also saw a significant reduction in FeNO levels in the primary study group. From baseline to week 12, the participants saw FeNO levels fall below the threshold for type 2 inflammation, with an average improvement in FeNO levels by -20.59.
The safety results were generally consistent with the known safety profile of dupilumab in patients aged 12 years and older with uncontrolled moderate-to-severe asthma. The overall rates of adverse events (AEs) were 83% for dupilumab and 80% for the placebo. The most commonly observed AEs with dupilumab included injection site reactions, viral upper respiratory tract infections, and eosinophilia.
Pivotal data at ATS 2021 show Dupixent (dupilumab) significantly reduced asthma attacks and improved lung function in children [news release]. Sanofi; May 17, 2021. https://www.sanofi.com/en/media-room/press-releases/2021/2021-05-17-16-00-00-2230876. Accessed May 20, 2021.