Originally published on Sanofi.com.
Dupixent® (dupilumab) showed positive topline results in Phase 3 trial of children aged 6 to 11 years with severe atopic dermatitis
- U.S. FDA submission for children planned for 4Q 2019
PARIS and TARRYTOWN, NY – August 6, 2019 – A pivotal Phase 3 trial evaluating Dupixent® (dupilumab) to treat severe atopic dermatitis in children aged 6 to 11 years met its primary and secondary endpoints. Dupixent is the first and only biologic to show positive results in this pediatric atopic dermatitis population.
The topline data show that for children with severe atopic dermatitis (covering nearly 60% of their skin surface on average), adding Dupixent to standard-of-care topical corticosteroids (TCS) significantly improved measures of overall disease severity, skin clearing, itching and health-related quality of life, compared to TCS alone. In addition, the safety data were consistent with the previously documented safety profile of Dupixent in older populations, including a numerically lower rate of skin infections compared to placebo.
“The results from this trial, the first to assess a biologic medicine in children under 12 with atopic dermatitis, are very important because of the significant unmet needs in this patient population. Children in the trial had suffered from severe atopic dermatitis for most of their lives,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron. “The trial showed that Dupixent significantly improved outcomes and quality of life, with no new safety signals.
Dupixent is a fully-human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) proteins. Data from Dupixent clinical trials have shown that IL-4 and IL-13 are key drivers of the type 2 inflammation that plays a major role in atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP).
“In this trial, children with severe atopic dermatitis had uncontrolled disease covering, on average, nearly 60% of their skin. The unrelenting symptoms of this disease, which impact not just the child but the whole family, include widespread rashes, intense and persistent itching, and skin lesions,” said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. “Symptoms of severe atopic dermatitis can take a toll on children both physically and emotionally. We are encouraged by these results, which demonstrate that Dupixent improved skin lesions, reduced itching, cleared the skin and importantly, improved health-related quality of life measures for these young patients.”
The primary endpoints assessed the proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and 75% improvement in Eczema Area and Severity Index (EASI-75, the co-primary endpoint outside of the U.S.) at 16 weeks.
Results at 16 weeks included:
- 33% of patients who received Dupixent every four weeks (300 mg) and 30% of patients who received Dupixent every two weeks (100 mg or 200 mg, based on weight) achieved clear or almost clear skin (IGA; score of 0 or 1), compared to 11% for placebo (p<0.0001 and p=0.0004, respectively).
- 70% of patients who received Dupixent every four weeks and 67% of patients who received Dupixent every two weeks achieved 75% or greater skin improvement (EASI-75), compared to 27% for placebo (p<0.0001 for both).
- The average EASI score improvement from baseline was 82% in the Dupixent every four weeks group and 78% in the Dupixent every two weeks group, compared to 49% for placebo (p<0.0001 for both).
- Dupixent demonstrated significant itch relief, and also improved measures of patient-reported outcomes, such as anxiety, depression and health-related quality of life of parents and family members.
For the 16-week treatment period, the overall rates of adverse events were 65% for Dupixent every four weeks, 67% for Dupixent every two weeks and 73% for placebo. Adverse events that were more commonly observed with Dupixent included conjunctivitis (7% for Dupixent every four weeks, 15% for Dupixent every two weeks and 4% for placebo), nasopharyngitis (13% for Dupixent every four weeks, 7% for Dupixent every two weeks and 7% placebo) and injection site reactions (10% for Dupixent every four weeks, 11% for Dupixent every two weeks and 6% for placebo). Additional prespecified adverse events included skin infections (6% for Dupixent every four weeks, 8% for Dupixent every two weeks and 13% for placebo) and herpes viral infections (2% for Dupixent every four weeks, 3% for Dupixent every two weeks and 5% for placebo).
Detailed results from this trial will be presented at a future medical meeting and data will be submitted to regulatory authorities, starting with the U.S. Food and Drug Administration (FDA) in 4Q 2019. In 2016, the FDA granted Breakthrough Therapy designation for Dupixent for the treatment of moderate-to-severe (12 to 17 years of age) and severe (6 months to 11 years of age) atopic dermatitis. The efficacy and safety of Dupixent in children below the age of 12 has not been reviewed by any regulatory authority.
About the Dupixent Pediatric Trial
The Phase 3, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of Dupixent combined with TCS in children with severe atopic dermatitis. The trial enrolled 367 patients aged 6 to 11 years with severe atopic dermatitis whose disease could not be adequately controlled with topical medications. In total, 92% of these patients suffered from at least one concurrent condition such as allergic rhinitis, asthma and food allergy.
All patients received TCS throughout the trial. Patients were randomized into one of three treatment groups for the 16-week treatment period: Dupixent subcutaneous injection 300 mg every four weeks (with an initial dose of 600 mg); Dupixent 100 mg or 200 mg every two weeks, based on weight (100 mg for <30 kg, 200 mg for >= 30 kg), with an initial dose of 200 mg or 400 mg, respectively; and placebo every two or four weeks.
Dupilumab Development Program
In addition to the currently approved indications, Sanofi and Regeneron are also studying dupilumab in a broad range of clinical development programs for diseases driven by allergic and other type 2 inflammation, including pediatric asthma and atopic dermatitis (6 to 11 years of age, Phase 3), pediatric atopic dermatitis (6 months to 5 years of age, Phase 2/3), eosinophilic esophagitis (Phase 2/3), chronic obstructive pulmonary disease (Phase 3) and food and environmental allergies (Phase 2). Dupilumab is also being studied in combination with REGN3500 (SAR440340), which targets IL-33. These potential uses are investigational and the safety and efficacy have not been evaluated by any regulatory authority.
Dupilumab is being jointly developed by Sanofi and Regeneron under global collaboration agreement.
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