Arcutis Biotherapeutics has announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for roflumilast cream 0.05% (ZORYVE) for the treatment of mild to moderate atopic dermatitis (AD) in children aged 2 to 5 years. The sNDA is supported by data from the pivotal Phase 3 INTEGUMENT-PED trial, demonstrating the efficacy and safety of the topical phosphodiesterase-4 (PDE4) inhibitor in this young patient population.
The INTEGUMENT-PED trial, a multicenter, randomized, double-blind, vehicle-controlled study, involved 652 children with mild to moderate AD. Results showed that 25.4% of children treated with roflumilast cream achieved vIGA-AD Success (defined as a Validated Investigator Global Assessment-Atopic Dermatitis score of "Clear" or "Almost Clear" with a minimum 2-grade improvement from baseline) at week 4, compared to 10.7% in the vehicle-treated group (p<0.0001). Significant improvements were observed as early as week 1, with 35.3% of children experiencing a notable reduction in itch by week 4.
Clinical Efficacy and Safety
The study also met its secondary endpoints, with a significantly higher proportion of patients in the roflumilast arm achieving EASI-75 (75% improvement in Eczema Area and Severity Index) at week 4 (39.4% versus 20.6% in the vehicle arm, p<0.0001). Rapid improvement in pruritus was observed, with 35.3% of children achieving a ≥4-point reduction in Worst Itch-Numeric Rating Scale (WI-NRS) scores by week 4, compared to 18.0% in the vehicle group (p=0.0002).
The safety profile of roflumilast cream 0.05% was favorable, with adverse events, including upper respiratory tract infection, diarrhea, and vomiting, occurring at rates consistent with prior studies. Long-term safety was further demonstrated in the INTEGUMENT-OLE open-label extension study, which involved 562 patients treated for up to 52 weeks.
Addressing Unmet Needs in Pediatric AD
Atopic dermatitis affects approximately 1.8 million children aged 2 to 5 years in the United States, often resulting in impaired quality of life for both patients and their caregivers. Current treatment options for this age group are limited, with concerns surrounding the long-term use of topical corticosteroids. Roflumilast, a PDE4 inhibitor, offers a non-steroidal approach by targeting intracellular enzymes to decrease pro-inflammatory mediators and increase anti-inflammatory mediators.
"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," said Rocco Serrao, MD, FAAD, of DOCS Dermatology and an investigator in the INTEGUMENT-PED and INTEGUMENT-OLE studies. "Data from the pivotal trial demonstrated that roflumilast cream 0.05% provided consistent and rapid relief, and was well-tolerated."
Potential Impact on Treatment Landscape
If approved, roflumilast cream 0.05% would offer a new topical option with the potential to advance the standard of care for young patients with AD, providing fast relief from the burdensome symptoms of the condition. The once-daily application and favorable safety profile may enhance adherence among pediatric patients and caregivers.
"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," said Patrick Burnett, MD, PhD, FAAD, chief medical officer at Arcutis. "We look forward to the FDA’s potential approval of roflumilast cream 0.05% anticipated later this year."
