FDA Accepts sNDA for Roflumilast Cream 0.05% to Treat Atopic Dermatitis in Children Aged 2 to 5 Years

Arcutis Biotherapeutics today announced submission of a supplemental New Drug Application (sNDA) to the US FDA for roflumilast cream 0.05%, for topical treatment of atopic dermatitis (AD) in children between ages 2 and 5 years.

Roflumilast, a once-daily, next generation phosphodiesterase 4 (PDE4) inhibitor, is approved in a formulation of 0.15% for topical treatment of mild to moderate AD in individuals 6 years of age and older. The 0.05% potency, if approved, “would offer a new topical option with the potential to advance the standard of care for these young patients,” Rocco Serrao, MD, an investigator for the INTEGUMENT-PED and INTEGUMENT-OLE clinical trials evaluating the cream for the younger pediatric population, said in the Arcutis news release.1

Estimates are that approximately 1.8 million children with AD are treated with topical therapies in the US. “When choosing a therapy for very young children living with AD, 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,” Serrao stressed in the statement.1 

Favorable data to support the Arcutis sNDA come from the pivotal phase 3 INTEGUMENT-PED vehicle-controlled trial, a long-term extension (LTE) study, and a phase 2 pharmacokinetic study, according to the news release. The 652 children enrolled in INTEGUMENT-PED were aged 2 to 5 years and had a mean AD body surface area (BSA) of 22% (range, 3% to 82%). After 4 weeks of treatment, 25.4% of children treated with roflumilast 0.05% achieved validated Investigator Global Assessment – Atopic Dermatitis (vIGA-AD) Success, with a score reflecting “clear” or “almost clear” skin and a 2-grade improvement from baseline. Just 10.7% of children treated with vehicle reached the same endpoint (P <.001). Importantly, investigators observed symptom improvements after only 1 week of treatment, Arcutis said.1

Researchers also reported significant improvements at all time points for all secondary study endpoints, which included vIGA-AD of clear or almost clear and vIGA-AD success by week 1. Further, after 4 weeks of treatment, more than one-third (35.3%) of participants treated with active study drug who had elevated baseline scores on the Worst Itch Numeric Scale (WI-NRS) had a 4-point reduction in the score vs 18.0% of children treated with vehicle (nominal P =.0002). (WI-NRS scores provided by caregivers.)1

The tolerability of roflumilast 0.05% was favorable, according to the news release, with a safety profile in the 2- to 5-year-old INTEGUMENT-PED cohort consistent with that established in adults and older pediatric study participants with mild/moderate AD who were treated with roflumilast 0.15%. The most frequent adverse events observed in the roflumilast-treated group that occurred more often than in the vehicle-treated arm were upper respiratory infection, diarrhea, and vomiting.

Data were also included from the INTEGUMENT-OLE long-term open label study that found 53.6% of individuals who were rolled over from the INTEGUMENT-PED roflumilast treatment arm achieved vIGA-AD success at 56 weeks.2 Nearly three-quarters (71.9%) of those participants achieved EASI-75 (Eczema Area and Severity Index) at week 56. Investigators did not report any new safety signals.2

Roflumilast cream was created to deliver the active medication while avoiding disruption of the skin barrier and without sensitizing excipients and irritants, according to Frank Watanabe, president and CEO of Arcutis. “This lower concentration of roflumilast cream was intentionally formulated for the needs of younger children with AD and demonstrates our commitment to serving this vulnerable patient population,” Watanabe said in the press release.1

In July 2024, roflumilast cream 0.15% received FDA approval as a once daily and steroid-free cream for rapid disease clearance and significant reduction in itch and for long-term disease control in individuals aged 6 years and older.3

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. News release. Arcutis Biotherapeutics. December 16, 2024. Accessed December 16, 2024. https://investors.arcutis.com/news-releases/news-release-details/arcutis-submits-zoryver-roflumilast-cream-005-supplemental-new
2. Arcutis announces positive long-term results of roflumilast cream 0.05% show durable and improved efficacy over time and favorable safety profile in treatment of children aged 2 to 5 with mild to moderate atopic dermatitis. News release. Arcutis Biotherapeutics. August 28, 2024. Accessed December 16, 2024. https://www.arcutis.com/arcutis-announces-positive-long-term-results-of-roflumilast-cream-0-05-show-durable-and-improved-efficacy-over-time-and-favorable-safety-profile-in-treatment-of-children-aged-2-to-5-with-mild-to-moder/
3. FDA approved Arcutis’ Zoryve (roflumilast) Cream 0.15% for the treatment of atopic dermatitis in adults and children down to 6 years of age. Arcutis Biotherapeutics. July 9, 2024. Accessed December 16, 2024.https://www.arcutis.com/fda-approves-arcutis-zoryve-roflumilast-cream-0-15-for-the-treatment-of-atopic-dermatitis-in-adults-and-children-down-to-6-years-of-age/