A 200 mg dose of the monoclonal antibody was also shown to significantly reduce ashtma exacerbations over 1 year versus placebo.
Jorge Maspero, MD, MS
Just 2 weeks before the US Food and Drug Administration is set to rule on its supplemental biologics application as an add-on asthma therapy in adolescents and adults, dupilumab (Dupixent) has phase 3 data showing its efficacy in reducing severe exacerbations and improving lung function in certain adolescent patients with asthma.
In new data from Sanofi and Regeneron Pharmaceuticals’ LIBERTY ASTHMA program, the anti-interleukin 4 (IL-4) monoclonal antibody was shown to significantly improve lung function in adolescent patients with uncontrolled, moderate-to-severe asthma—on 2 different dosing regimens.
The study results were presented at the 2018 CHEST Annual Meeting in San Antonio, TX. Investigators, led by Jorge Maspero, MD, MS, investigators assessed the 107 adolescents of the 1902 total (5.6%) enrolled in the LIBERTY ASTHMA trials. Qualified patients were aged 12-17 years old, with no minimum baseline eosinophil requirement, diagnosed with asthma uncontrolled with medium-to-high dose inhaled corticosteroids (ICS) plus 1-2 controllers.
Patients received either 200 mg or 300 mg dupilumab every 2 weeks, or matching placebo, for 52 weeks. Both dupilumab treatment arms had 34 patients, and 39 patients were split between the 2 placebo regimens. The patient population was 64.5% male, with a mean baseline forced expiratory volume in 1 second (FEV1) of 2.33 L. Mean predicted FEV1 was 70.45%, and mean exacerbations in the year prior to baseline was 1.91 per patient.
Investigators assessed for the annualized rate of severe exacerbations using a regression model, as well as the change in pre-bronchodilator FEV1 and percentage predicted FEV1 at week 12, using a mixed-effect model with repeated measures approach.
Dupilumab 200 mg patients had reported a 46.4% reduced annualized severe exacerbation rates. However, adolescent patients on 300 mg dupilumab did not report a treatment effect versus placebo. Investigators noted, though, that the unadjusted exacerbation rate for patients on 300 mg therapy was .46, and .76 for those on matching placebo.
They theorized this disparity was due to the small sample size, as well as an imbalance in the number of prior exacerbation events between treated patients (1.53) and patients on placebo (2.22).
Both dupilumab treatment groups did manage to report significant improvements in FEV1 from baseline to week 12 versus placebo. The 200 mg patients (.36 [95% CI: .12 - .61]) fared better than 300 mg patients (.27 [95% CI: .02 - .52]), though all adolescents treated with dupilumab reported greater FEV1 than treated adults from the LIBERTY ASTHMA trials (.12 [95 CI%: .07 - .18] for both 200 and 300 mg; P < .05).
The only adverse event to have occurred in more than 10% of the adolescent patient population was injection site reactions—it was reported in 9% and 0% of the 200 mg and 300 mg dupilumab groups, respectively.
The trend of issuing biologics capable of inhibiting the pathways of both IL-4 and IL-13—as dupilumab does—has been widely discussed at CHEST 2018 in the same vein as emerging type 2 asthma therapies. As a therapy already approved for improperly controlled atopic dermatitis and being investigated for pediatric atopic dermatitis, nasal polyps, and eosinophilic esophagitis, the newest LIBERTY data simply widens the antibody’s reach across inflammatory disease.
The study, "Dupilumab Reduceds Severe Exacerbation Rate and Improves Lung Function in Adolescent Patients with Uncontrolled, Moderate-to-Severe Asthma: From the LIBERTY ASTHMA QUEST Study," was presented at CHEST 2018.
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