Regulatory Decision Summary for Dupixent

The purpose of this submission was to expand the recommended use of Dupixent (dupilumab injection) to include the treatment of adult patients with prurigo nodularis. After evaluation of the submitted data package, Health Canada authorized Dupixent for the treatment of adult patients with moderate-to-severe prurigo nodularis (PN) whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

The submission was reviewed using the international review work sharing model with the Access Consortium. SwissMedic led the review of the clinical modules. Health Canada’s assessment is based on peer review and subsequent communications with the SwissMedic.

Prurigo Nodularis (PN) is an uncommon, chronic inflammatory skin disease. It is characterized by chronic pruritus (≥6 weeks), presence of nodular skin lesions that are symmetrically distributed on areas of the trunk and extremities, and signs of repeated scratching, picking, or rubbing. Severely debilitating itch is considered the most burdensome symptom. PN is associated with high disease burden and several co-morbidities.

Authorization was based on two Phase 3, 24-week, randomized, double-blind, placebo-controlled studies (PRIME and PRIME2). Patients (n = 311) aged ≥18 years of age with moderate-to-severe prurigo nodularis whose disease was not adequately controlled with topical prescription therapies or for whom those therapies were not advisable were randomized to receive either Dupixent (n = 153) or placebo (n = 158). The dose administered was an initial loading dose of 600 mg administered subcutaneously, followed by 300 mg every other week.

The primary efficacy endpoint was the proportion of patients with improvement (reduction) in worst-itch numeric rating scale (WI-NRS) by ≥4 points. WI-NRS is a self-reported itch score based on a rating scale from 0 (“no itch”) to 10 (“worse imaginable itch”). This primary endpoint was evaluated at Week 12 in PRIME2 and at Week 24 in PRIME. A key secondary endpoint evaluated was the proportion of patients with Investigator Global Assessment Prurigo Nodularis-Stage (IGA PN-S) 0 or 1 score at Week 24. The IGA PN-S is a scale that measures the approximate number of nodules using a 5-point scale from 0 (clear) to 4 (severe). There was a statistically significant and clinically meaningful benefit for dupilumab compared to placebo for these endpoints.

The safety profile of Dupixent is well-established. The observed safety profile of dupilumab in adult patients with PN is considered consistent with that reported for the other authorized indications. No additional risks were identified in PRIME and PRIME 2 studies. Commonly reported treatment emergent adverse events (TEAEs) (≥2%) that occurred ≥1% more frequently in PN patients receiving dupilumab included: nasopharyngitis, dizziness, diarrhea, eczema, myalgia, conjunctivitis/conjunctivitis allergic, blood creatine phosphokinase increased, accidental overdose and herpes infection.

An updated 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.

Overall, based on the data evaluated as part of this submission, the benefit-risk profile of Dupixent used as per the recommended dosing regimen, is considered to be favourable for the treatment of adult patients with moderate-to-severe PN. A Notice of Compliance (NOC) was issued.

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