Add-on treatment with dupilumab may improve lung function in children aged 6-11 years with uncontrolled moderate to severe type 2 inflammatory asthma, results from a randomized, placebo-controlled, phase 3 study show.
Dr. Leonard B. Bacharier
Improvements in lung function parameters were observed as early as 2 weeks and persisted over the 52-week treatment period among children in the LIBERTY ASTHMA VOYAGE study, according to investigator Leonard B. Bacharier, MD, of Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tenn.
“Dupilumab led to clinically meaningful rapid and sustained improvements in lung function parameters,” Dr. Bacharier said in an online poster presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.
The improvements in forced expiratory volume in 1 second (FEV1) and other measures reported for children with moderate to severe asthma who have the type 2 phenotype, which is the most common driver of pediatric asthma, according to Dr. Bacharier.
“Many children with moderate to severe asthma have abnormal lung function, and this can be a risk factor for future lung disease in adulthood,” Dr. Bacharier said in his presentation.
The VOYAGE continues
The findings presented at the meeting build on another report earlier this year from the LIBERTY ASTHMA VOYAGE study demonstrating that add-on dupilumab treatment led to a significant improvement versus placebo in FEV1 up to 12 weeks.
“We now have a long term data on this drug as well, showing its efficacy over a period of time,” said Muhammad Adrish, MD, MBA, FCCP, associate professor of pulmonary, critical care and sleep medicine at Baylor College of Medicine, Houston.
“I think that’s pretty exciting, and that’s another step towards precision medicine in treatment of asthma,” Dr. Adrish, who is Vice-Chair of CHEST’s Airways Disorders NetWork Steering Committee and was not involved in the study.
Dupilumab received Food and Drug Administration approval in 2018 as add-on maintenance therapy for the treatment of patients aged 12 years or older with moderate to severe asthma that has an eosinophilic phenotype or that is dependent on oral corticosteroid treatment.
In March 2021, Sanofi and Regeneron announced that the FDA had accepted for review a supplemental Biologics License Application for dupilumab as an add-on treatment in children aged 6-11 years with uncontrolled moderate to severe asthma.
That sBLA is supported by data from the LIBERTY ASTHMA VOYAGE study, Sanofi and Regeneron said.
In results of the phase 3 study that Dr. Bacharier presented in May at the American Thoracic Society International Conference, add-on dupilumab dosed every 2 weeks significant improved percent predicted prebronchodilator FEV1 by an additional 5.21 percentage points versus placebo at week 12.
Dupilumab and the type 2 phenotype
The new data reported at the CHEST meeting come from a prespecified analysis evaluating the impact of dupilumab on lung function over a 52-week treatment period in patients with a T2 inflammatory asthma phenotype.
“Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and -13, key and central drivers of T2 inflammation in multiple diseases,” Dr. Bacharier and coinvestigators reported in their study abstract.
Of 408 patients in the study, 350 met the T2 phenotype criteria, including 236 in the dupilumab arm and 114 in the placebo arm.
Patients met T2 phenotype criteria if they had blood eosinophils of at least 150 cells/mcL or fractional exhaled nitric oxide FeNO of at least 20 parts per billion at baseline, investigators said.
Dr. Bacharier and coinvestigators reported on several different endpoints, including absolute and percent predicted prebronchodilator FEV1, percent predicted postbronchodilator FEV1, prebronchodilator forced expiratory flow at 25%-75% of pulmonary volume (FEF25%-75%), and forced vital capacity (FVC).
Dupilumab, when compared with placebo, significantly improved prebronchodilator FEV1 in pediatric patients with uncontrolled moderate to severe type 2 asthma, according to Dr. Bacharier.
“Patients receiving dupilumab experienced rapid improvements by week 2, and this was sustained for up to 52 weeks,” he said.
The prebronchodilator FEV1 improved from baseline for dupilumab versus placebo, with a least squares mean difference of 0.06 L at week 2, which reached 0.17 L by week 52, according to their data. Similarly, postbronchodilator FEV1 improved from baseline for dupilumab, with a least square mean difference versus placebo of 0.09 L at week 52.
Dupilumab compared to placebo also significantly improved percent predicted FEF25%-75%, and percent predicted FVC over the 52-week treatment period, according to Dr. Bacharier.
“Dupilumab led to significant, rapid, and sustained improvements in multiple aspects of lung function in children aged 6-11 years,” Dr. Bacharier added in a CHEST press release that described the findings.
The LIBERTY ASTHMA VOYAGE study was sponsored by Sanofi and Regeneron Pharmaceuticals. Dr. Bacharier provided disclosures related to AstraZeneca, GlaxoSmithKline, Regeneron Pharmaceuticals, Sanofi, CF Foundation, DBV Technologies, NIH, and Vectura.