Roflumilast cream 0.05% (Zoryve, Arcutis Biotherapeutics, Inc.) improved atopic dermatitis (AD) across all primary and secondary efficacy endpoints, with significant improvement as early as Week 1 on multiple efficacy endpoints in kids aged 2 to 5, according to the INTEGUMENT-PED Trial.
Roflumilast cream is a next-generation topical phosphodiesterase 4 (PDE4) inhibitor. Roflumilast cream 0.3% is approved by the U.S. Food and Drug Administration (FDA) for the topical treatment of plaque psoriasis, including intertriginous areas, in patients 6 years of age and older. Roflumilast cream 0.15% is approved by the FDA for the topical treatment of mild to moderate AD in patients 6 years of age and older. Arcutis Biotherapeutics submitted a supplemental new drug application to the FDA for roflumilast cream 0.05% for treating pediatric mild to moderate atopic dermatitis in December 2024.
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, with a mean Body Surface Area (BSA) of 22% overall and a range from 3% to 82%.
As previously reported, at Week 4, 25.4% of children treated with roflumilast cream 0.05% achieved vIGA-AD 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, compared to 10.7% of children treated with vehicle, with significant improvements seen as early as Week 1.
Other key findings included:
- Rapid improvement in itch was observed in children treated with roflumilast cream 0.05% within 24 hours of the first application, as measured by the change from baseline in daily Worst Itch Numeric Scale (WI-NRS), compared with vehicle.
- Fully 35.3% of children treated with roflumilast cream 0.05% achieved a four-point reduction in WI-NRS at Week 4 vs. 18.0% for vehicle-treated subjects.
- 39.4% of children treated with roflumilast cream achieved a 75% improvement in the Eczema Area and Severity Index (EASI-75) at Week 4 compared to 20.6% treated with vehicle. Significant improvements based on EASI-75 were observed with roflumilast cream compared to vehicle as early as Week 1.
- 35.4% of children treated with roflumilast cream 0.05% achieved a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of ‘clear’ or ‘almost clear’ at Week 4, with significant improvements seen as early as Week 1.
- Roflumilast cream 0.05% was very well-tolerated. The incidence of Treatment-Emergent Adverse Events (TEAEs) was low and similar in both active treatment and vehicle arms. The most frequent adverse events in the roflumilast cream arm (≥2%) included upper respiratory tract infection, diarrhea, and vomiting. All individual AEs occurred in <4.1% of patients.
- Safety and tolerability results were consistent with previous trials of roflumilast cream 0.15% in patients aged ≥6 years with AD.
“Results from the INTEGUMENT-PED trial demonstrate that ZORYVE cream 0.05% can quickly and reliably improve the symptoms of AD, especially itch,” says lead study author Lawrence F. Eichenfield, MD, Chief of Pediatric and Adolescent Dermatology at Rady Children’s Hospital-San Diego in San Diego, CA. ”The publication of these results and the entire clinical development program highlight that ZORYVE cream 0.05%, if approved, could fill a significant gap in the current treatment landscape for a once-daily steroid-free topical therapy that is appropriate for both the short and long-term management of AD, key concerns for young patients and their caregivers.”
“On the heels of our recent submission of a sNDA to the FDA for ZORYVE cream 0.05%, we’re proud to share the full INTEGUMENT-PED results published in Pediatric Dermatology with the dermatology community, supporting the well-established efficacy, safety, and tolerability profile of this lower concentration of ZORYVE cream,” says Patrick Burnett, MD, PhD, FAAD, Chief Medical Officer at Arcutis. “We’re committed to bringing forth meaningful innovation and addressing the significant unmet need for topical treatments of young children living with the challenges of AD. We look forward to the FDA’s potential approval of ZORYVE cream 0.05% anticipated later this year.”
