FDA Receives sNDA for Roflumilast Cream Treatment of Children with Atopic Dermatitis

Arcutis Biotherapeutics, Inc. has submitted a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) for once-daily roflumilast (Zoryve) cream 0.05% treatment of mild-to-moderate atopic dermatitis in children aged 2 - 5 years.¹

The December 16 announcement of Arcutis’s sNDA submission follows recent findings suggesting strong results among those in the aforementioned age range using this topical treatment. Roflumilast cream, a next-generation phosphodiesterase 4 (PDE4) inhibitor formulated to address mild-to-moderate atopic dermatitis.

“When choosing a therapy for very young children living with [atopic dermatitis], healthcare providers and caregivers have to account for unique considerations for pediatric patients, including sensitive skin, and select a medication that is appropriate for long-term use by a child with a chronic skin condition,” Rocco Serrao, MD, FAAD, of DOCS Dermatology and INTEGUMENT-PED and INTEGUMENT-OLE investigator, said in a statement.¹

Atopic dermatitis, also known as eczema, is a chronic inflammatory skin condition impacted by a set of genetic factors and presenting with recurring symptoms such as a red, intensely itchy rash that can appear anywhere on the body and can significantly impact the quality of life for young patients. Roflumilast cream, as an advanced PDE4 inhibitor, targets an enzyme involved in increasing pro-inflammatory mediators and thereby reducing anti-inflammatory ones.

Previously, FDA officials approved roflumilast 0.3% for the treatment of individuals 6 years of age and older with plaque psoriasis, including those with the disease in intertriginous areas.² They also approved roflumilast 0.15% for those with mild-to-moderate eczema in the same age range.

The new sNDA application was backed by a variety of recent clinical data, including results from a pivotal phase 3 analysis, a long-term extension trial, and a phase 1 pharmacokinetic analysis. In the phase 3 INTEGUMENT-PED trial, the investigators had assessed 652 children aged 2 - 5 with an average affected body surface area (BSA) of 22%, ranging from 3% - 82%.

Following a 4-week course of treatment, 25.4% of these children tgiven roflumilast 0.05% were noted as having achieved vIGA-AD Success—a validated Investigator Global Assessment of 'clear' or 'almost clear' with a 2-grade level of improvement in their atopic dermatitis.

This was compared to 10.7% among those in the placebo arm of the study (P < .0001). Improvements in trial participants' eczema were shown to be noticeable to the research team as early as the first week.

In terms of secondary endpoints, including vIGA-AD success and pruritus relief, the investigative team also reported significantly better results at all of the available time points. Specifically, they found that 35.3% of children with a baseline Worst Itch Numeric Scale (WI-NRS) score of ≥4 had a 4-point reduction in their pruritus severity by the 4-week mark, compared to 18% of those in the placebo arm (P = .0002).

The treatment was well-tolerated, with the safety profile in children aged 2 - 5 aligning with the established safety data from older patients using higher concentrations. Common adverse events observed by the team in the analyses included such events as upper respiratory tract infections, diarrhea, and vomiting.

Additional support for this new sNDA resulted from the INTEGUMENT-OLE open-label extension study, during which 562 children aged 2 - 5 were treated for up to 52 weeks. Results further reinforced the medication's efficacy and safety.

“Data from the pivotal trial demonstrated that roflumilast cream 0.05% provided consistent and rapid relief, and was well-tolerated,” Serrao said in his statement. “If approved, roflumilast cream 0.05% would offer a new topical option with the potential to advance the standard of care for these young patients, offering fast relief to the children and their families from the onerous symptoms of [atopic dermatitis].”¹

References

1. ^{Arcutis Submits ZORYVE® (roflumilast) Cream 0.05% Supplemental New Drug Application to the FDA for the Treatment of Children Aged 2 to 5 with Mild to Moderate Atopic Dermatitis. Arcutis Biotherapeutics, Inc. December 16, 2024. https://www.biospace.com/press-releases/arcutis-submits-zoryve-roflumilast-cream-0-05-supplemental-new-drug-application-to-the-fda-for-the-treatment-of-children-aged-2-to-5-with-mild-to-moderate-atopic-dermatitis. Date accessed: December 16, 2024.}
2. ^{FDA approvesArcutis’ ZORYVE (roflumilast) cream 0.3% for the treatment of psoriasis in children ages 6 to 11. Arcutis Biotherapeutics. News release. October 6, 2023. Date accessed: October 6, 2023. https://investors.arcutis.com/news-releases/news-release-details/fda-approves-arcutis-zoryver-roflumilast-cream-03-treatment. Date accessed: December 16, 2024.}