Regulatory Decision Summary for Dupixent

The purpose of this Supplement to a New Drug Submission (SNDS) was to seek market authorization for Dupixent (dupilumab injection) for the treatment of adult and adolescent patients with eosinophilic esophagitis (EoE).

Eosinophilic esophagitis (EoE) is a serious, chronic, immune-mediated condition of the esophagus that can cause symptoms of esophageal dysfunction. EoE is histologically characterized by type 2 inflammation with abnormal preponderance of eosinophilic infiltration of the esophagus. Persistent eosinophilic inflammation increases the risk of fibrostenosis of the esophagus and the frequency of symptoms of esophagus dysfunction, including dysphagia and food impaction. As EoE progresses, fibrostenosis of the esophagus can occur, which increases the frequency of food impactions, which in some instances, requires manual removal by a healthcare professional in an urgent care setting to relieve the impaction. Patients with EoE require repeated endoscopic evaluations, sometimes requiring repeat esophageal dilations intervention. Health Canada granted this application priority review.

The benefits of Dupixent are primarily demonstrated by a phase 3, three-part protocol study (Study-EE-1774) consisting of two independent randomized, double-blind, parallel-group, multicentre, placebo-controlled, 24-week treatment studies (Part A and Part B) in separate groups of adult and adolescent subjects with a confirmed diagnosis of EoE that was non-responsive to high-dose proton pump inhibitor (PPI) therapy.

Study EE-1774 demonstrated that a greater proportion of subjects achieved histological remission (i.e., reduction in peak esophageal intraepithelial eosinophil count below pre-specified threshold) at Week 24 with dupilumab 300 mg QW versus placebo. Additionally, subjects receiving dupilumab 300 mg QW experienced a statistically significant and clinically meaningful improvement in self-reported dysphagia symptom questionnaire (DSQ) score – a questionnaire designed to measure difficulty swallowing associated with EoE – from baseline to Week 24; subjects receiving placebo did not experience a clinically meaningful change in DSQ score. Furthermore, subjects receiving dupilumab 300 mg QW experienced a favourable change in endoscopic scoring of inflammatory and remodeling features of EoE compared to placebo at Week 24 as measured by the Eosinophilic Esophagitis Endoscopic Reference Score (EoE-EREFS) total score.

The treatment response in favour of Dupixent observed in the adolescent subpopulation was consistent with overall population.

In the primary safety pool (n = 320), dupilumab 300 mg QW was well-tolerated over 24 weeks, with few serious AEs, AEs of special interest, or discontinuations due to AEs. All cases of injection site reaction were non-serious and mild, and cases of infections were generally mild and did not lead to study discontinuation. While observed at a lower frequency than in previous dupilumab clinical development programs, arthralgia was reported in 2.5% of subjects treated with dupilumab 300 mg QW and was the only AE that led to study discontinuation by more than one subject. Overall, serious AEs were uncommon, and no serious AE was reported more than once in a single treatment arm. Injection site reactions were more frequently reported in adolescents receiving dupilumab vs. placebo; however, no pronounced risk was identified in the adolescent sub-population. While long-term safety data reflective of the intended chronic treatment with Dupixent remains limited, no additional risks were identified in subjects receiving up to 52 weeks of treatment for EoE. The safety profile of dupilumab in patients with EoE was consistent with that reported for the other approved indications.

Overall, based on the data evaluated as part of this submission, the Biologic and Radiopharmaceutical Drugs Directorate considers the benefit-risk profile of Dupixent 300 mg administered once weekly (QW) to be favourable for the treatment of adult and adolescent patients, weighing at least 40 kg, with eosinophilic esophagitis.