Regeneron Pharmaceuticals, Inc. and Sanofi announced that the U.S. Food and Drug Administration (FDA) has approved Dupixent (dupilumab) for children aged 6 to 11 years with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Dupixent is the only biologic medicine approved for this population.
“This approval brings the paradigm-changing efficacy and established safety profile of Dupixent to children with moderate-to-severe atopic dermatitis. This young, vulnerable population struggles with debilitating symptoms and disease covering over half of their body, impacting them and their families who spend countless hours helping them manage their disease,” said George D. Yancopoulos, M.D., Ph.D., Co-founder, President and Chief Scientific Officer at Regeneron. “We continue to study Dupixent in even younger children with uncontrolled moderate-to-severe atopic dermatitis from 6 months to 5 years old, as well as in children with uncontrolled, persistent asthma. Additionally, we are investigating Dupixent in other diseases driven by type 2 inflammation including eosinophilic esophagitis, food and environmental allergies, chronic obstructive pulmonary disease and other dermatologic diseases.”
Dupixent is a fully-human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) proteins, and is not an immunosuppressant. 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). Across all approved indications globally, more than 150,000 patients have been treated with Dupixent.
“This FDA approval is another milestone in the journey for Dupixent as an innovative biologic treatment for atopic dermatitis and other conditions driven in part by type 2 inflammation,” said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. “Caregivers of children with moderate-to-severe atopic dermatitis and their physicians now have access to a first-in-class biologic with a proven safety profile, a factor that often plays a critical role in treatment decisions for younger patients. Additionally, improvements in itch and disease severity were observed as early as two weeks after the first dose and continued throughout active treatment, which is important for these children and their families.”
The FDA evaluated the Dupixent application under Priority Review, which is reserved for medicines that represent potentially significant improvements in efficacy or safety in treating serious conditions. The FDA previously granted Breakthrough Therapy designation to Dupixent for the treatment of severe atopic dermatitis in children 6 months to 11 years of age not well controlled on topical prescription medications. The Breakthrough Therapy designation was created to expedite the development and review of drugs developed for serious or life-threatening conditions.
Atopic dermatitis, the most common form of eczema, is a chronic inflammatory disease that often appears as a rash on the skin. Moderate-to-severe atopic dermatitis is characterized by rashes that can potentially cover much of the body and can include intense, persistent itching, skin lesions and skin dryness, cracking, redness or darkness, crusting and oozing. Itch is one of the most burdensome symptoms for patients and can be debilitating.
Dupixent comes in two doses, prescribed based on weight (300 mg every four weeks for children ≥15 to <30 kg and 200 mg every two weeks for children ≥30 to <60 kg, following an initial loading dose) as a pre-filled syringe for pediatric patients aged 6 to 11 years.
The FDA approval is based on data that includes pivotal Phase 3 results on the efficacy and safety of Dupixent combined with topical corticosteroids (TCS) compared to TCS alone in children with severe atopic dermatitis. In the trial, children treated with Dupixent and TCS experienced significant improvements in overall disease severity, skin clearance and itch.
Results at 16 weeks showed:
- 84% improvement in average EASI (Eczema Area and Severity Index) score from baseline in patients who received Dupixent every four weeks and 80% in patients who received Dupixent every two weeks, compared to 49% and 48% for TCS alone, respectively.
- 75% of patients who received Dupixent every four weeks and 75% of patients who received Dupixent every two weeks achieved EASI-75 (Eczema Area and Severity Index-75), compared to 28% and 26% for TCS alone, respectively.
- 54% of patients who received Dupixent every four weeks and 61% of patients who received Dupixent every two weeks experienced at least a 4-point reduction in itch intensity on a 0 to 10-point scale (weekly average of daily Peak Pruritus Numerical Rating Scale), compared to 12% and 13% for TCS alone, respectively.
- 30% of patients who received Dupixent every four weeks and 39% of patients who received Dupixent every two weeks achieved clear or almost clear skin (Investigator’s Global Assessment or IGA), compared to 13% and 10% for TCS alone, respectively.
The safety profile of Dupixent with TCS was similar to what was observed in adults and adolescents with atopic dermatitis, and consistent through 52 weeks. Safety data over the 16-week treatment period showed:
- Overall rates of adverse events (AEs) were 65% for Dupixent every four weeks, 61% for Dupixent every two weeks, and 72% and 75% for TCS alone, respectively.
- AEs that were more commonly observed with Dupixent included upper respiratory tract infections (15% for Dupixent every four weeks, 9% for Dupixent every two weeks, and 8% and 12% for TCS alone, respectively), injection site reactions (10% for Dupixent every four weeks, 14% for Dupixent every two weeks, and 7% and 5% for TCS alone, respectively), nasopharyngitis (10% for Dupixent every four weeks, 3% for Dupixent every two weeks, and 3% and 10% for TCS alone, respectively), conjunctivitis (7% for Dupixent every four weeks, 9% for Dupixent every two weeks, and 3% and 5% for TCS alone, respectively), vomiting (5% for Dupixent every four weeks, 7% for Dupixent every two weeks, and 7% and 7% for TCS alone, respectively) and fever (5% for Dupixent every four weeks, 2% for Dupixent every two weeks, and 7% and 0% for TCS alone, respectively).
Additional prespecified AEs across all weight groups and doses included skin infections (6% for Dupixent every four weeks, 8% for Dupixent every two weeks, and 13% for TCS alone), which is noteworthy because patients with atopic dermatitis have an increased risk of skin infections. In adult atopic dermatitis trials, the incidence of serious skin infections was 57% less with Dupixent compared to the control groups. In addition, in the pediatric trial (6-11 years of age), herpes viral infections occurred in 0% of Dupixent patients every four weeks, 2% of Dupixent patients every two weeks, and 5% for patients on TCS alone.
Dupixent has been studied in more than 8,000 patients ages 6 years and older across more than 40 clinical trials.