Regulatory Decision Summary for Zoryve

The purpose of this Supplement to a New Drug Submission (SNDS) for Zoryve was to propose the addition of a new dose strength (i.e., 0.15% weight in weight [w/w]) for the following new indication: Zoryve (roflumilast cream, 0.15%) is indicated for topical treatment of mild to moderate atopic dermatitis, in patients 6 years of age and older.

This SNDS was filed to obtain market authorization, pursuant to section C.08.0004 of the Food and Drugs Regulations, for Zoryve filed by Arcutis Canada, Inc.

The Sponsor was seeking to expand the indication for Zoryve to include patients 6 years of age and older with mild to moderate atopic dermatitis.

Two multicenter, randomized, double blind, vehicle-controlled trials (INTEGUMENT 1 and INTEGUMENT 2) enrolled a total of 1,337 subjects with mild to moderate atopic dermatitis. The study population ranged in age from 6 to 91 years, with 615 subjects aged 6 to 17 years, 657 subjects aged 18 to 64 years, and 65 subjects aged 65 years or older.

Subjects were randomized 2:1 to receive Zoryve cream 0.15% or vehicle applied once daily for 4 weeks. The primary endpoint was the proportion of subjects who achieved validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) treatment success, defined as a vIGA-AD score of clear (0) or almost clear (1), plus at least a 2 grade vIGA-AD score improvement from baseline, at Week 4. Secondary endpoints included the proportion of subjects that achieved vIGA-AD success at Weeks 2 and 1, at least a 75% reduction in Eczema Area and Severity Index (EASI-75) at Week 4, and Worst Itch-Numeric Rating Scale (WI- NRS) success at Weeks 4, 2, and 1. WI-NRS success was defined as a reduction of at least 4 points from baseline in subjects 12 years of age or older with a baseline WI NRS score of at least 4.

The results of the primary efficacy endpoint analysis in both pivotal trials demonstrated that patients treated with Zoryve cream 0.15% had a clinically meaningful and statistically significant improvement in vIGA-AD success at Week 4 (32.0% and 28.9%) when compared with those treated with vehicle (15.2% and 12.0%). Zoryve cream 0.15% showed significant improvement based on vIGA-AD success compared to vehicle as early as 2 weeks in both pivotal trials. At Week 4, the proportion of patients with EASI‑75 was significantly larger in the Zoryve treatment group compared with the vehicle group. More patients treated with Zoryve achieved statistical significance in WI‑NRS success compared to those receiving vehicle.

In terms of safety, the most common adverse drug reactions reported in clinical trials among patients with atopic dermatitis 6 years of age and older treated with Zoryve cream 0.15% are headache and nausea. There was no evidence of a meaningfully different adverse reaction profile in patients aged 6 to 17, relative to adults. The safety profile of Zoryve remains unchanged following this submission.

An updated Risk Management Plan was submitted and reviewed by the Marketed Health Products Directorate.

The chemistry and manufacturing information submitted for Zoryve has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

The final labelling and Product Monograph were considered acceptable.

Overall, the benefit-harm-uncertainty profile of Zoryve was favourable for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Thus, a Notice of Compliance (NOC) was recommended for Zoryve.

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