Regeneron Pharmaceuticals, Inc. and Sanofi announced that the European Commission has approved Dupixent (dupilumab) for the treatment of moderate-to-severe chronic spontaneous urticaria (CSU) in children aged 2 to 11 years with inadequate response to histamine-1 antihistamines (H1AH) and who are naïve to anti-immunoglobulin E (IgE) therapy for CSU. This expands the previous approval in the EU for adults and adolescents aged 12 years and older with CSU, a chronic, inflammatory skin disease that causes sudden and debilitating hives and recurring itch. The approval in the EU is based on data from the LIBERTY-CUPID clinical trial program.
This includes an extrapolation of efficacy data in adults from two Phase 3 trials (Study A and Study C) complemented by pharmacokinetic, safety and efficacy data from the single-arm CUPIDKids Phase 3 trial in children aged 2 to 11 years with CSU. Study A and Study C demonstrated Dupixent significantly reduced urticaria activity (a composite of itch and hives) and individual measures of itch and hive severity compared with placebo at week 24. Dupixent also increased the percentage of patients with well-controlled disease and complete response at week 24 compared with placebo.
Safety results from Study A, Study C and CUPIDKids were generally consistent with the known safety profile of Dupixent in its approved dermatological indications. The most common adverse reactions for Dupixent overall are injection site reactions, conjunctivitis, conjunctivitis allergic, arthralgia, oral herpes and eosinophilia. Additional adverse reactions of injection site induration, injection site dermatitis and injection site bruising or hematoma were reported in the CSU adult and adolescent trials.
The adverse event more commonly observed with Dupixent (=5%) than placebo in Study A and Study C in adults and adolescents with CSU was COVID-19. Safety data for children aged 2 to 11 years with CSU were generally consistent with the safety profile for adult and adolescent patients with CSU treated with Dupixent. In the U.S., the supplemental Biologics License Application (sBLA) for Dupixent has been accepted for review in certain children aged 2 to 11 years with CSU.
Dupixent is currently approved for CSU in certain adults and adolescents in many jurisdictions, including the U.S. and Japan. CSU is a chronic, inflammatory skin disease driven in part by type 2 inflammation, which causes sudden and debilitating hives and recurring itch. CSU is typically treated with H1AH, medicines that target H1 receptors on cells to control symptoms of itch and urticaria.
However, the disease remains uncontrolled despite H1AH treatment in many patients, some of whom are left with limited alternative treatment options. These individuals continue to experience symptoms that can be debilitating and significantly impact their quality of life. The LIBERTY-CUPID Phase 3 program evaluating Dupixent for CSU in children aged 2 to 11 years includes Study A, Study C and CUPIDKids.
CUPIDKids was a single arm clinical trial that assessed the safety, efficacy and pharmacokinetics of Dupixent in children aged 2 to 11 years with CSU who remained symptomatic despite the use of antihistamines. During the 24-week treatment period, Dupixent was administered at 200 mg every two or four weeks or 300 mg every four weeks, with or without an initial loading dose, based on age and weight. The primary endpoint measured the serum concentration of Dupixent over time, including Ctrough (lowest concentration before the next dose) at week 12 and week 24.
Study A and Study C were replicate, double-blind, placebo-controlled clinical trials that assessed Dupixent as an add-on therapy to standard-of-care antihistamines compared to antihistamines alone in patients aged 6 years and older who remained symptomatic despite the use of antihistamines and were naïve to anti-IgE therapy. During the 24-week treatment period in both trials, all patients received an initial loading dose followed by either 300 mg Dupixent every two weeks, or for pediatric patients weighing 30 kg to Change from baseline in itch (measured by the weekly itch severity score [ISS7], 0-21 scale), the key secondary endpoint. Change from baseline in hives (measured by the weekly hive severity score [HSS7], 0-21 scale), secondary endpoint.
Proportion of patients achieving well-controlled disease status (UAS7 =6). Proportion of patients with complete response (UAS7=0). Dupixent is an injection administered under the skin (subcutaneous injection) at different injection sites.
In children aged 2 to 11 years with CSU who remain symptomatic despite H1AH treatment, Dupixent is administered based on age and weight.
