Health Canada will review Arcutis Canada, Inc.’s Supplement to a New Drug Submission (SNDS) for roflumilast cream 0.15% for the treatment of mild to moderate atopic dermatitis (AD) in adults and children ages 6 years and older.
The SNDS includes data from the “INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis” (INTEGUMENT-1 and INTEGUMENT-2) trials, two identical Phase 3, parallel group, double blind, vehicle-controlled trials in which roflumilast cream 0.15% or vehicle was applied once-daily for four weeks to individuals 6 years of age and older with mild to moderate AD involving ≥3% body surface area.
Both studies met the primary endpoint of IGA Success, defined as a validated Investigator Global Assessment – Atopic Dermatitis (vIGA-AD) score of ‘clear’ or ‘almost clear’ plus a 2-grade improvement from baseline at Week 4 (INTEGUMENT-1: 32.0% roflumilast cream vs. 15.2% vehicle; INTEGUMENT-2: 28.9% roflumilast cream vs. 12.0% vehicle).
More than 30% of individuals treated with roflumilast cream in each study achieved Worst Itch-Numeric Rating Scale (WI-NRS) Success at Week 4. WI NRS Success is defined as achievement of at least a 4-point reduction on the WI-NRS 0 (no itch) to 10 (worst imaginable itch) scale (in individuals 12 and older who had a baseline WI-NRS score of at least 4). Rapid and significant improvement in itch was observed in individuals treated with roflumilast cream 0.15% compared with vehicle as early as 24 hours following the first application, as measured by the least-squares (LS) mean change from baseline in daily WI-NRS scores between the two groups.
In both studies, approximately 40% of children and adults treated with roflumilast cream 0.15% achieved a vIGA-AD score of Clear (0) or Almost Clear (1) at Week 4 (INTEGUMENT-1: 41.5% vs. 25.2%; INTEGUMENT-2: 39% vs. 16.9%), with significant improvement as early as Week 1.
In addition, more than 40% of children and adults treated with roflumilast cream 0.15% achieved a 75% reduction in Eczema Area and Severity Index (EASI-75) at Week 4 compared to vehicle (INTEGUMENT-1: 43.2% vs. 22.0%; INTEGUMENT-2: 42.0% vs. 19.7%). Significant improvements in EASI-75 were observed with roflumilast cream 0.15% as early as Week 1 in both studies.
Roflumilast cream 0.15% was generally well tolerated. The incidence of Treatment Emergent Adverse Events (TEAEs) was low in both active treatment and vehicle arms, with most TEAEs assessed as mild to moderate in severity. There were no adverse reactions in the combined Phase 3 pivotal trials that occurred in more than 2.9% of subjects in either arm. The most common adverse reactions included headache (2.9%), nausea (1.9%), application site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%).
The Health Canada submission is also supported by data from a Phase 2 dose ranging study, an open label extension study in which patients were treated for up to 52 weeks, and two Phase 1 pharmacokinetic studies.
“The INTEGUMENT studies have demonstrated the excellent efficacy and tolerability of roflumilast cream 0.15% in both adults and children, which is particularly important given the need for patients to have more non-steroidal topical options for the management of atopic dermatitis,” says Dr. Melinda Gooderham, Medical Director at the SKiN Centre for Dermatology and a principal Canadian investigator in the Phase 3 pivotal INTEGUMENT trials, in a news release. “Trial data showed when applied once daily, roflumilast cream was effective at improving AD over multiple endpoints, rapidly improving symptoms and alleviating itch, a particularly distressing symptom for patients, within as little as 24 hours. The promising combination of efficacy and tolerability shown in the pivotal trials along with the favourable long term safety profile suggest that if approved, roflumilast cream has the potential to improve patient adherence and elevate the management of atopic dermatitis with an option that aligns with patient preferences and concerns.”
Roflumilast cream 0.15% is uniquely formulated with HydroARQ Technology as a non-greasy emollient cream designed to absorb quickly and spread easily without disrupting the skin barrier, which is crucial for maintaining skin health in individuals with AD. It is formulated at physiological skin pH and is free of sensitizing excipients and irritants, such as propylene glycol, polyethylene glycol, isopropyl alcohol, ethanol, or fragrances that have the potential to aggravate skin sensitivity and trigger reaction.
“Roflumilast cream 0.15% is emerging as a promising advancement developed with the needs of atopic dermatitis patients in mind since it is formulated without ingredients that could compromise the skin barrier and without common contact allergens,” says Dr. Chih-ho Hong, a principal investigator for the INTEGUMENT trials in Canada.
