Fully 25.4% of children treated once daily with roflumilast cream 0.05% achieved Investigator Global Assessment (IGA) Success compared to 10.7% of children treated with vehicle at Week 4, with significant improvements seen as early as Week 1.

Arcutis Biotherapeutics, Inc.’s roflumilast cream 0.05% met all primary endpoint and all secondary endpoints in children aged 2 to 5 years with mild to moderate atopic dermatitis (AD), according to results from the INTEGUMENT-PED pivotal Phase 3 trial. 

In the study, 25.4% of children treated with roflumilast cream achieved onvestigator global assessment (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, compared to 10.7% treated with vehicle, with significant improvements seen as early as Week 1.

INTEGUMENT-PED enrolled 652 children ages 2 to 5, with a mean Body Surface Area (BSA) of 22% overall, and a range from 3% to 82%. The new data reinforce the efficacy, safety and tolerability profile of roflumilast cream in atopic dermatitis across the INTEGUMENT program.

“The positive findings from this study of roflumilast cream are highly consistent with the findings from the INTEGUMENT-1 and INTEGUMENT-2 studies,” says Adelaide A. Hebert, MD, Chief of Pediatric Dermatology at McGovern Medical School at UTHealth Houston, and INTEGUMENT-PED investigator, in a news release. “These results further reinforce the safety and efficacy profile of roflumilast cream as a potential treatment option, if approved, for pediatric atopic dermatitis down to 2 years of age.”

Roflumilast cream met all secondary endpoints, with significant improvements seen across all time points including vIGA-AD success and vIGA-AD of ‘clear’ and ‘almost clear’ at Week 1. In the study, 39.4% of children treated with roflumilast cream 0.05% achieved a 75% improvement in EASI-75 at Week 4 compared to 20.6% treated with vehicle. In addition, 35.3% of children treated with roflumilast cream achieved a four-point reduction in Worst Itch Numeric Scale (WI-NRS) at Week 4 (vs. 18.0% for vehicle-treated subjects.

“EASI-75 has emerged as an important endpoint in clinical trials and reflects clinically meaningful responses in the real world,” says Jonathan Silverberg, MD, PhD, MPH, FAAD, Professor, Director of Clinical Research, and Director of Patch Testing at George Washington University School of Medicine and Health Sciences, Washington, DC. “EASI incorporates body surface area, and higher body surface area involvement is an important consideration for the severity and impact of the disease for patients suffering from pediatric atopic dermatitis.”

Roflumilast cream was very well-tolerated. Overall, the incidence of adverse events in INTEGUMENT-PED was low, and the only adverse event occurring in ≥3% of subjects in either arm was upper respiratory tract infection. The most frequent adverse events in the roflumilast arm (≥2%) included upper respiratory tract infection, pyrexia, diarrhea, and vomiting. Of children who were randomized to roflumilast cream in the study, 93.8% completed the full four weeks, and there were few discontinuations due to adverse events (1.1% and 1.9% in the roflumilast cream and vehicle groups, respectively). Of the children who completed INTEGUMENT-PED, 93.4% elected to continue open label, long-term treatment in the INTEGUMENT-OLE study.

“Roflumilast cream was formulated with the atopic dermatitis patient in mind, delivering drug without disrupting the skin barrier or the use of sensitizing excipients and irritants. The consistent safety and tolerability profile of roflumilast cream sets our next generation PDE4 inhibitor apart,” says Patrick Burnett, MD, PhD, FAAD, chief medical officer at Arcutis. “In addition, roflumilast cream provided rapid improvement and control in atopic dermatitis as well as quick reduction of itch, which provides the positive feedback loop to the parent and caregiver that the treatment is working and an incentive to maintain therapy over time.”

The Company recently announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for roflumilast cream 0.15% for the treatment of mild to moderate atopic dermatitis in adults and children ages 6 years and older. 

Following the potential approval of roflumilast cream 0.15% and based on these positive results, Arcutis intends to submit an sNDA for roflumilast cream 0.05% for the treatment of mild to moderate atopic dermatitis in children ages 2 to 5 years.

About INTEGUMENT-PED

The “INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis in PEDiatric patients” (INTEGUMENT-PED) is a Phase 3, parallel group, double blind, vehicle-controlled trial in which roflumilast cream 0.05% or vehicle was applied once daily for four weeks to children 2 to 5 years of age with mild to moderate AD. A total of 652 children were enrolled in the study. The primary endpoint was IGA Success, defined as a vIGA-AD score of ‘clear’ or ‘almost clear’ plus a 2-grade improvement from baseline at Week 4. Multiple secondary endpoints were also evaluated, including the proportion of subjects who attain at least a 75% reduction in the EASI-75 at Week 4.