FDA Grants Priority Review to Dupixent (dupilumab) for Moderate-to-Severe Atopic Dermatitis in Children Aged 6 Months to 5 Years

Infant Atopic Dermatitis (Image Source: atopicdermatitis.net)

News on February 17, 2022 /BioValleyBIOON/ -- Sanofi and its partner Regeneron recently announced jointly that the U.S. Food and Drug Administration (FDA) has accepted a supplemental Biologics License Application (sBLA) for Dupixent (Chinese trade name: 达必妥, generic name: dupilumab) and granted it priority review: Dupixent is proposed as an add-on maintenance therapy for children aged 6 months to 5 years with moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies or when these therapies are not advisable.FDAThe target action date for this sBLA has been set for June 9, 2022.

If approved, Dupixent will become the first biologic available in the U.S. for treating moderate-to-severe atopic dermatitis in young children whose condition is uncontrolled. Currently, Dupixent remains the only biologic approved for this indication in patients aged 6 years and older.In 2016, the United StatesFDADupixent has been granted Breakthrough Therapy Designation (BTD) for the treatment of severe atopic dermatitis in children aged 6 months to 11 years.

This sBLA is based on the positive results from the pivotal Phase 3 LIBERTY AD PRESCHOOL trial. The trial was conducted in children aged 6 months to 5 years with uncontrolled moderate to severe atopic dermatitis (AD), and the results showed:Compared with standard-of-care topical corticosteroids (TCS), the combination of Dupixent and TCS significantly improved skin clearance, reduced overall disease severity, and alleviated itching.The safety observed in this trial is consistent with the well-established safety profile of Dupixent in adult, adolescent, and pediatric patients aged 6 years and above with atopic dermatitis. The most commonAdverse ReactionsIncluding conjunctivitis and herpesvirus infection.

Atopic Dermatitis (AD) is a chronic type 2 inflammatory skin disease. Symptoms appear in 85-90% of patients before the age of 5 (onset) and usually persist into adulthood. Symptoms include intense, persistent itching and skin lesions that can cover much of the body, leading to dry, cracked, painful, red or darkened skin, crusting, and oozing – while also increasing the risk of skin infections. Moderate to severe atopic dermatitis can also significantly impact the lives of young children and their parents or caregivers, including their emotions, sleep patterns, and quality of life. Current treatment options for this age group are primarily topical steroids, but long-term use may raise safety concerns and affect growth.

Mechanism of Action of Dupixent (Image Source: dupixenthcp.com)

LIBERTY AD PRESCHOOL is a two-part Phase 2/3 trial. The Phase 3 randomized, double-blind, placebo-controlled trial (Part B) was conducted in 162 children aged 6 months to 5 years with uncontrolled moderate-to-severe atopic dermatitis, evaluating the efficacy and safety of adding Dupixent to low-potency TCS standard care versus low-potency TCS alone (placebo). The primary endpoints were the proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 (clear skin) or 1 (almost clear skin) and a 75% improvement in the Eczema Area and Severity Index (EASI-75) at week 16. EASI measures the extent and severity of the disease using a 0-10 numerical rating scale. Patients treated with Dupixent received 200mg (for 5 kg ≤ weight < 15 kg) or 300mg (for 15 kg ≤ weight < 30 kg) every four weeks. Of the 162 patients enrolled in the trial, on average, atopic dermatitis covered 58% of their body surface area, and 29% had previously used systemic immunosuppressants. Additionally, 81% of the patients had at least one concurrent type 2 inflammatory disease.

The pre-specified primary analysis showed that at 16 weeks, 28% of patients in the Dupixent group achieved complete or almost complete clearance of skin lesions (IGA 0/1, primary endpoint), compared to 4% in the placebo group (p≤0.0001). In addition, 53% of patients in the Dupixent group achieved ≥75% improvement in overall disease from baseline (EASI-75, co-primary endpoint outside the U.S.), compared to 11% in the placebo group (p≤0.0001).

Patients in the Dupixent group experienced an average EASI improvement of 70% from baseline, compared to 20% in the placebo group (p≤0.0001). Patients in the Dupixent group also showed an average pruritus improvement of 49% from baseline, compared to 2% in the placebo group (p＜0.0001). Additionally, significant improvements were observed in the Dupixent group compared to the placebo group in patient-reported outcomes (including sleep, skin pain, and health-related quality of life) as well as caregiver-reported health-related quality of life measures.

In terms of safety, the overall incidence of adverse events (AEs) during the 16-week treatment period was 64% for Dupixent and 74% for placebo. The most common adverse events and those of particular concern in the Dupixent group versus the placebo group included nasopharyngitis (8% vs 9%), upper respiratory tract infection (6% vs 8%), conjunctivitis (5% vs 0%), and herpesvirus infection (6% vs 5%).

Dupixent targets the key drivers of type 2 inflammation. It is a fully human monoclonal antibody that specifically inhibits overactive signaling of two key proteins, IL-4 and IL-13. IL-4/IL-13 are two cytokines considered to be key drivers of intrinsic inflammation in allergic diseases and other type 2 inflammatory conditions, including atopic dermatitis.Asthma, Eosinophilic Esophagitis, Grass Allergy, Peanut Allergy, etc.

Dupixent was launched at the end of March 2017 and has currently been approved to treat three diseases caused by type 2 inflammation: moderate to severe atopic dermatitis (patients ≥6 years old), moderate to severeAsthma(≥6 years old patients), chronic rhinosinusitis with nasal polyps (CRSwNP, adult patients).

In China, in June 2020, Dupixent (Dupilumab) was approved by the National Medical Products Administration (NMPA) for the treatment of adult patients with moderate-to-severe atopic dermatitis (AD). Dupixent is the world's first and only targeted biologic therapy approved for treating adult patients with moderate-to-severe atopic dermatitis, addressing an unmet clinical need in China by providing rapid, significant, and sustained improvement in skin lesions and pruritus symptoms for patients with atopic dermatitis. Thanks to the regulatory reform, Dupixent was approved two years ahead of schedule in China, offering Chinese patients a new treatment option.

Currently, Sanofi and Regeneron are also conducting an extensive clinical program to evaluate Dupixent in the treatment of diseases caused by allergies and other type 2 inflammations, including: chronic obstructive pulmonary disease (Phase 3), pediatric atopic dermatitis (6 months to 5 years, Phase 3), eosinophilic esophagitis (Phase 3), bullous pemphigoid (Phase 3), prurigo nodularis (Phase 3), chronic spontaneous urticaria (Phase 3), chronic inducible urticaria (Phase 3), chronic rhinosinusitis without nasal polyps (Phase 3), allergic fungal rhinosinusitis (Phase 3), allergic bronchopulmonary aspergillosis (Phase 3), and peanut allergy (Phase 2). (Bioon.com)

Source of the original text:FDA ACCEPTS DUPIXENT (DUPILUMAB) FOR PRIORITY REVIEW IN CHILDREN AGED 6 MONTHS TO 5 YEARS WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS