Regulatory Decision Summary for Dupixent

Atopic dermatitis (AD), also known as atopic eczema, is a chronic, relapsing, inflammation of the skin that is characterized by intractable pruritus, extensive xerosis (abnormally dry and scaly skin), and skin lesions. AD affects 15-30% of children and 2-10% of adults in developed countries.

The clinical efficacy results for Dupixent are based on clinical data from three randomized, double-blind, placebo-controlled trials, SOLO 1, SOLO 2, and CHRONOS that enrolled a total of 2,119 patients, 18 years of age and older, with moderate-to-severe atopic dermatitis not adequately controlled by topical medications.

In all three trials, subjects in the Dupixent group received subcutaneous injections of Dupixent 600 mg at Week 0, followed by 300 mg every other week. In the monotherapy trials (SOLO 1 and SOLO 2), subjects received Dupixent or placebo for 16 weeks. In the concomitant therapy trial (CHRONOS), subjects received Dupixent or placebo with concomitant topical corticosteroids (TCS) and, as needed, topical calcineurin inhibitors for problem areas only, for 52 weeks.

All three trials assessed the primary endpoint, the change from baseline to Week 16 in the proportion of subjects with an Investigators Global Assessment (IGA) score of 0 or 1, and at least a 2-point improvement. Other endpoints included the proportion of subjects with EASI-75 (improvement of at least 75% in Eczema Area and Severity Index (EASI) score from baseline), and reduction in itch as defined by at least a 4-point improvement in the peak pruritus Numerical Rating Scale (NRS) from baseline to Week 16.

Dupixent was clinically and statistically superior to placebo in all three clinical studies in the target atopic dermatitis (AD) population for the primary endpoint and for key secondary endpoints.

Anti-drug antibodies (ADA) were detected in <2% of patients. Neutralizing antibodies were not generally associated with loss of efficacy, except in patients who exhibited high titer ADA responses.

The safety profile of Dupixent in the target population, as evaluated in over 2,500 patients in three pivotal trials and over 52 weeks of treatment (740 patients), is acceptable. The safety profiles in the monotherapy and concomitant topical corticosteroid trials were similar. An increased incidence of conjunctivitis, keratitis, blepharitis, and dry eye in the Dupixent arms, of moderate severity, did not require treatment discontinuation. Dupixent was generally well tolerated. The safety profile of Dupixent + TCS through week 52 is consistent with the safety profile observed at week 16.

The benefits of Dupixent, in the target population and for the indication authorized, outweigh its risks. The overall benefit/risk profile of Dupixent is considered to be favourable.

In order to ensure that the benefits of Dupixent continue to outweigh any risk after authorization, Health Canada has required several post-approval activities to be carried out and a Risk Management Plan.

For more information on Health Canadas decision, please view the Summary Basis of Decision.