Sanofi’s Dupixent® Recommended by EU for Treating Children Aged 6–11 with Atopic Dermatitis; Approved in China for Adults

October 17, 2020 News /BioValleyBIOON/ -- Sanofi and Regeneron recently jointly announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending approval for expanding the indicated population of Dupixent (Chinese brand name: Dabito; generic name: dupilumab) to include children aged 6 to 11 years with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy. The CHMP’s opinion represents the final step in the marketing authorization procedure prior to approval by the European Commission (EC). The CHMP’s opinion will now be submitted to the EC for review; the EC typically adopts the CHMP’s opinion and issues a final decision within two months.

In June this year, Dupixent received U.S.FDAApproval was granted to expand the indicated population to include pediatric patients aged 6–11 years with moderate-to-severe AD. Notably, Dupixent is the first and only biologic approved in the United States for patients aged ≥6 years and in the European Union for patients aged ≥12 years with uncontrolled moderate-to-severe AD.

In China, Dupixent® (dupilumab) was approved by the National Medical Products Administration this June for the treatment of adult patients with moderate-to-severe atopic dermatitis (AD). As the first and only targeted biologic agent approved globally for treating moderate-to-severe atopic dermatitis in adults, Dupixent® addresses an unmet clinical need in China, providing rapid, significant, and sustained improvement in skin lesions and pruritus symptoms among patients with atopic dermatitis. Benefiting from regulatory reforms, Dupixent® received approval in China two years ahead of schedule, offering Chinese patients a novel therapeutic option.

Atopic dermatitis (AD) is a refractory, recurrent, inflammatory skin disease characterized by severe pruritus and rash that recur frequently. Patients often have comorbid allergic rhinitis,Asthmaand other atopic diseases. Most patients experience pain and discomfort caused by skin cracking, crusting, and exudation. If not effectively controlled, these symptoms can affect patients' emotional and psychological well-being, leading to anxiety, depression, and feelings of loneliness. Some patients have reported that relentless, severe itching lasting up to 12 hours is most unbearable at night, forcing them to scratch continuously and use pain to mask the itch, making a normal night's sleep a luxury.

Dupixent is a fully human monoclonal antibody that inhibits IL-4 and IL-13 signaling; it is not an immunosuppressant. From DupixentClinical TrialData indicate that IL-4/IL-13 are key drivers of type 2 inflammation in atopic dermatitis,Asthma, plays a key role in chronic rhinosinusitis with nasal polyps (CRSwNP). Among these three globally approved indications, more than 170,000 patients have been treated with Dupixent.

Atopic Dermatitis (Image Source: icresearch.net)

The U.S. FDA approval for the treatment of children aged 6–11 years and the positive opinion from the EU CHMP are both based on the results of a pivotal Phase III pediatric clinical study of Dupixent (NCT03345914). This was a randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of Dupixent in combination with standard-of-care topical corticosteroids (TCS) for the treatment of severe atopic dermatitis (AD) in children (with an average body surface area involvement of nearly 60%). The study enrolled a total of 367 patients aged 6–11 years with severe AD whose condition was not adequately controlled with topical medications. Overall, 92% of patients had at least one comorbidity, such as allergic rhinitis,Asthmaand food allergies.

Throughout the study, all patients received topical corticosteroid (TCS) therapy. These patients were randomized into three treatment groups for a 16-week treatment period: Group 1 received Dupixent 300 mg via subcutaneous injection every 4 weeks (with an initial loading dose of 600 mg); Group 2 received Dupixent 100 mg or 200 mg via subcutaneous injection every 2 weeks (weight-adjusted dosing: 100 mg for <30 kg and 200 mg for ≥30 kg), with initial loading doses of 200 mg or 400 mg, respectively; Group 3 received placebo via subcutaneous injection every 2 weeks or every 4 weeks. The primary endpoint was the proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) within 16 weeks, along with a 75% improvement in the Eczema Area and Severity Index (EASI-75, the co-primary endpoint outside the United States).

The results showed that the study met both the primary and secondary endpoints. The data demonstrated that, in pediatric patients with severe atopic dermatitis (AD), Dupixent combined with topical corticosteroids (TCS) significantly improved outcomes in overall disease severity, skin clearance, pruritus, and health-related quality of life compared to TCS alone. Furthermore, the safety profile was consistent with previously reported data in patients aged 12 years and older, including a numerically lower rate of skin infections compared to placebo.

Treatment outcomes at 16 weeks included: (1) 33% and 30% of patients in Group 1 and Group 2, respectively, achieved an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear), compared with 11% in the placebo group (p<0.0001 and p=0.0004, respectively). (2) 70% and 67% of patients in Group 1 and Group 2, respectively, achieved ≥75% improvement in skin clearance (EASI-75), compared with 27% in the placebo group (both p<0.0001). (3) The mean EASI scores improved by 82% and 78% from baseline in Group 1 and Group 2, respectively, compared with 49% in the placebo group (both p<0.0001). (4) Dupixent demonstrated significant pruritus relief and improved patient-reported outcomes, including anxiety, depression, and health-related quality of life for parents and family members.

During the 16-week treatment period, the overall incidence rates of adverse events were 65% in Group 1 and 67% in Group 2, compared with 73% in the placebo group. Adverse events more commonly associated with Dupixent treatment included conjunctivitis (7% in Group 1, 15% in Group 2, and 4% in the placebo group), nasopharyngitis (13% in Group 1, 7% in Group 2, and 7% in the placebo group), and injection-site reactions (10% in Group 1, 11% in Group 2, and 6% in the placebo group). Other prespecified adverse events included skin infections (6% in Group 1, 8% in Group 2, and 13% in the placebo group) and herpes viral infections (2% in Group 1, 3% in Group 2, and 5% in the placebo group).

Based on these results, Dupixent is the first biologic to demonstrate positive outcomes in this pediatric (aged 6–11 years) population with atopic dermatitis (AD).

Dupixent targets the key drivers of type 2 inflammation. This fully human monoclonal antibody specifically inhibits the overactivated signaling of two key proteins, IL-4 and IL-13. IL-4 and IL-13 are two inflammatory cytokines considered to be the key drivers of underlying inflammation in allergic diseases and other type 2 inflammatory conditions, including atopic dermatitis,Asthma, eosinophilic esophagitis, grass allergy, peanut allergy, etc.

Dupixent was launched in late March 2017, becoming the first biologic agent for the treatment of moderate-to-severe atopic dermatitis worldwide. To date, the drug has been approved in multiple countries and regions, including the United States, the European Union, and Japan. In the United States, Dupixent is currently approved for the treatment of three diseases driven by type 2 inflammation: moderate-to-severe atopic dermatitis (in patients aged ≥6 years), moderate-to-severeAsthma(≥12 years of age), chronic rhinosinusitis with nasal polyps (CRSwNP, adult patients).

Currently, Sanofi and Regeneron are also conducting an extensive clinical program to evaluate Dupixent for the treatment of diseases caused by allergies and other type 2 inflammation, including: pediatricAsthma(6–11 years, Phase III), pediatric atopic dermatitis (6 months to 5 years, Phase II/III), eosinophilic esophagitis (Phase III), chronic obstructive pulmonary disease (Phase III), bullous pemphigoid (Phase III), prurigo nodularis (Phase III), chronic spontaneous urticaria (Phase III), and food and environmental allergies (Phase II).

Dupixent is another major product co-developed by Sanofi and Regeneron following the PCSK9 inhibitor lipid-lowering drug Praluent, and it is poised to become a game-changing medication. Currently, the indications for Dupixent are steadily expanding. EvaluatePharma, a renowned pharmaceutical market research firm, previously predicted that the drug’s global sales could reach $8 billion in 2024. (Bioon.com)

Original Source: European advisory group backs expanded use of Regeneron/Sanofi's Dupixent