Regulatory Decision Summary for Dupixent

The purpose of this Supplement to a New Drug Submission - Priority Review (SNDS-PR) was to:

• seek market authorization for Dupixent (dupilumab injection) for the treatment of pediatric patients (1 years of age and older) with Eosinophilic Esophagitis (EoE).

• seek labelling updates to include longer-term efficacy and safety results from the main clinical study supporting authorization of EoE in adult and adolescents.

This submission was filed under the Priority Review Policy.

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, 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 in a phase 3, three-part protocol consisting of a randomized, double-blind, parallel-group, multicentre, placebo-controlled, 16-week treatment study (Part A) of pediatrics (children 1 to <12 years of age) with active EoE that were non-responsive to high-dose proton pump inhibitor (PPI) therapy. Subjects completing the 16-weeks of the double-blind treatment period in Part A were provided an option to enroll in a 36-week active treatment extension study (Part B).

Study EE-1877 Part A demonstrated that a statistically significant greater proportion of subjects achieved histological remission (i.e., peak esophageal intraepithelial eosinophil count ≤6 eos/hpf) at Week 16 with Dupixent versus placebo. Additionally, subjects receiving Dupixent had favourable change from baseline in the proportion of days with 1 or more EoE signs at Week 16 versus placebo. Furthermore, subjects receiving dupilumab experienced a favourable change in endoscopic scoring of inflammatory features of EoE compared to placebo at Week 16 as measured by the Eosinophilic Esophagitis Endoscopic Reference Score (EoE-EREFS) total score; no changes in remodeling features reflective of the characteristic pathophysiology of EoE were observed. The reduction in esophageal inflammation early in the disease course can limit – and possibly even prevent – the progression toward the development of irreversible structural remodelling features in patients with EoE.

In the pediatric EoE clinical programme, Dupixent was well-tolerated in subjects receiving treatment for up to 52 weeks. The incidence of adverse events (AEs) were generally consistent when comparing dupilumab to placebo, with few serious AEs, AEs of special interest, and discontinuations due to AEs reported. Treatment-emergent adverse events (TEAEs) were generally mild-to-moderate intensity, were non-serious, and did not require treatment discontinuation. The most frequently reported treatment-emergent AEs were COVID-19 infection, rash, injection site erythema, and headache. Despite the disproportionate incidence of COVID-19 infection in subjects receiving dupilumab compared to placebo, no causal association has been established. Serious AEs were generally reported as single incidences with no observable trend suggestive of a greater risk of serious AEs in subjects receiving dupilumab than placebo. Overall, identified risks are consistent with those observed in adults and considered sufficiently mitigated by product labelling and routine pharmacovigilance activities.

Overall, based on the data and information evaluated as part of this assessment, the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) considers there to be a favourable benefit-risk profile for Dupixent (dupilumab) in support of an extension to the authorized indication for the treatment of patients 1 year of age and older, weighing at least 15 kg, with EoE. Therefore, a Notice of Compliance (NOC) was recommended.

A Risk Management Plan (RMP) for Dupixent was reviewed by Health Canada and considered acceptable.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

For further details about Dupixent, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.