Regulatory Decision Summary for Zoryve

The purpose of this Supplement to a New Drug Submission (SNDS) was to obtain market authorization, pursuant to section C.08.0004 of the Food and Drugs Regulations, for Zoryve filed by Arcutis Canada, Inc.

This Supplement was filed for Zoryve (roflumilast foam 0.3%) for a new indication, topical treatment of plaque psoriasis of the scalp and body in patients 12 years of age and older. Upon review of the submitted data package, Health Canada authorized Zoryve as filed.

The proposed indication and dosing regimen of once daily topical administration were supported by a single pivotal, parallel-group, double-blind, vehicle-controlled Phase 3 study (ARQ-154-309, ARRECTOR). Adolescent (≥ 12 years of age) and adult (≥ 18 years of age) subjects (n = 432) with scalp psoriasis of at least moderate severity and body psoriasis of at least mild severity, involving up to 25% of body surface area (BSA) (not including the palms and soles) were administered either Zoryve foam or vehicle foam daily (QD) for 8 weeks. The co-primary endpoints investigated were Scalp-Investigator Global Assessment (S-IGA) success at Week 8 and Body-Investigator Global Assessment (B-IGA) success at Week 8.

The co-primary endpoints were met. A statistically significantly higher proportion of patients in the Zoryve foam group achieved S-IGA success at Week 8 (Zoryve foam 66.4% vs. Vehicle 27.8%, OR [97.5% confidence interval {CI} 5.19 {2.90, 9.31}], p< 0.0001) and B-IGA success at Week 8 (Zoryve foam 45.5% vs. Vehicle 20.1%, OR [97.5% CI] 3.17 [1.75, 5.73], p < 0.0001). Zoryve foam was statistically superior to Vehicle for key, multiplicity-controlled secondary efficacy endpoints, including achievement of Psoriasis Scalp Severity Index (PSSI)-75 and Psoriasis and Severity Index (PASI)-75 at Week 8, and achievement of a ≥ 4-point improvement in Scalp Itch-Numeric Rating Scale (SI-NRS) and Worst Itch-Numeric Rating Scale (WI-NRS).

Because the vehicle-controlled studies limited the total BSA affected by psoriasis (scalp and body) up to 25% (not including the palms and soles), the extrapolation to more extensive disease should be approached with caution.

Overall, Zoryve foam was well tolerated in both adolescents and adults. The majority of treatment-emergent adverse events (TEAEs) were mild or moderate and manageable; no life-threatening TEAEs or deaths occurred. The rate of serious TEAEs and discontinuations due to TEAEs was low. The most common TEAEs (more than 1%) were headache, diarrhea, nausea, and nasopharyngitis. Local tolerability was favorable, with investigator-rated assessments showing no evidence of irritation, and subject-rated assessments mostly reporting no sensation or mild, slight warming, tingling sensation. Limited moderate sensations (definite warm, tingling) were reported in the subject-rated local tolerability assessment.

Roflumilast is an inhibitor of phosphodiesterase 4 (PDE-4). Marketed oral PDE-4 inhibitors have been associated with psychiatric adverse events (AEs), including depression and weight loss. No signals of depression or suicidality in adults and adolescents, and no unintentional marked weight loss were observed in the clinical studies for Zoryve foam.

The long-term safety profile of Zoryve foam is supported by the established long-term safety for Zoryve cream in plaque psoriasis based on the composition of the formulations, same once-daily dosing regimen, similar pharmacokinetic profiles, and similar patient populations studied.

A limited number of adolescents (12 to 17 years of age) were enrolled in the clinical development program with Zoryve foam for the treatment of plaque psoriasis of the scalp and body. The pediatric indication is based on extrapolation from adult safety and efficacy data as per recommendations outlined in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E11 Clinical Investigation of Medicinal Products in the Pediatric Population (Addendum to E11). The criteria considered for the approval of pediatric indication were: 1) comparable pathophysiology and disease course of plaque psoriasis across the pediatric and adult patients; 2) demonstrated efficacy in vehicle-controlled studies (including in the adolescent group); 3) similar pharmacokinetic exposure between adults and adolescents; 4) comparable safety profile of roflumilast foam 0.3% in adults and adolescents; and 5) clinical experience with roflumilast cream 0.3% in this population.

Information related to pharmacokinetics, safety and efficacy of Zoryve foam for the treatment of plaque psoriasis of the scalp and body in patients ≥ 12 years were included in the Product Monograph.

There are no outstanding concerns at this point in time.

An updated Risk Management Plan (RMP) for Zoryve (roflumilast foam 0.3%) was reviewed by Health Canada and considered acceptable.

The final labelling and Product Monograph were considered acceptable.

Overall, the benefit-harm-uncertainty profile was favorable for Zoryve (roflumilast foam 0.3%) for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

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