FDA Accepts Roflumilast Cream sNDA in Atopic Dermatitis for Ages 2-5 Years

Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) for roflumilast cream 0.05% (Zoryve) for the treatment of mild to moderate atopic dermatitis in children aged 2 to 5 years old.

Announced by Arcutis Biotherapeutics on February 26, 2025, the application for the topical, once-daily, next generation phosphodiesterase-4 (PDE4) inhibitor has received a PDUFA target action date of October 13, 2025. According to the company’s release, the application is supported by positive findings from the phase 3 INTEGUMENT-PED trial, the INTEGUMENT-OLE study, and a phase 1 pharmacokinetic study.¹

“In clinical trials, investigational ZORYVE cream 0.05% has shown significant positive results in treating [atopic dermatitis] in children 2 to 5 years old. The data highlight the efficacy of the cream, along with its favorable safety and tolerability profile, which are critical when prescribing a long-term treatment for children with AD,” said Mercedes E. Gonzalez, MD, medical director of Pediatric Skin Research, LLC, and INTEGUMENT PED clinical trial investigator.¹ “In children, [atopic dermatitis] often occurs on sensitive areas like the face and neck. In addition to persistent itching and scratching, [atopic dermatitis] is associated with a lower quality of life for the affected child and caregiver. If approved, ZORYVE cream 0.05% will provide a new treatment option that offers long-term relief and can help alleviate the disease burden for children and their caregivers.”

The announcement from Arcutis Biotherapeutics comes less than a week after the publication of INTEGUMENT-PED data in Pediatric Dermatology. A phase 3, double-blind, parallel-group trial INTEGUMENT-PED evaluated the efficacy and safety of roflumilast cream 0.05% in 652 patients aged 2 to 5 years with mild-to-moderate atopic dermatitis. In total, 437 patients received roflumilast and 215 received a vehicle cream to be applied once daily for 4 weeks.^1,2

At week 4, significantly more patients in the roflumilast group achieved the trial’s primary endpoint of Validated Investigator Global Assessment for AD Success (25.4% vs. 10.7%; P < 0.0001). Secondary endpoint analysis also revealed greater improvements in EASI-75 (39.4% vs. 20.6%; P <.0001), Worst Itch-Numeric Rating Score Success (35.3% vs. 18.0%; P = .0002), and pruritus improvement within 24 hours (35.4 vs 13.6%; P = .0014) among the roflumilast group.²

“The publication of these results and the entire clinical development program highlight that [roflumilast] 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 [atopic dermatitis], key concerns for young patients and their caregivers," said Lawrence Eichenfield, MD, professor of dermatology and pediatrics at Rady Children's Hospital and the University of California, San Diego, in a statement from Arcutis Biotherapeutics.³

Safety analysis indicated adverse events occurred among 29.7% of the roflumilast group and 21.9% of the vehicle group. However, 98.9% of events were classified as mild or moderate. Investigators noted stinging and burning discomfort was minimal, with less than 1% of caregivers reporting definite discomfort.²

At the time the sNDA filing for roflumilast 0.05% cream in patients aged 2 to 5 years with mild to moderate atopic dermatitis, roflumilast cream 0.15% had already received approval for management of atopic dermatitis in adults and children down to 6 years of age.

“Topical treatments prescribed to young [atopic dermatitis] patients today can have significant shortcomings, which lead to difficult trade-offs between efficacy, safety, and tolerability. Our clinical trials demonstrate that investigational ZORYVE cream 0.05% effectively relieves the itchy rash of [atopic dermatitis] in these very young children, with a safe and tolerable profile that dermatology clinicians trust from their experience with our ZORYVE portfolio,” said Frank Watanabe, president and CEO of Arcutis.¹ “Our commitment to helping people with immune-mediated dermatological diseases is underscored by our efforts to provide an alternative to steroids with a new targeted topical therapy option with the potential to advance the standard of care for the approximately 1.8 million children between the ages of 2 and 5 living with [atopic dermatitis].”

References:

1. Arcutis Biotherapeutics. U.S. FDA accepts Supplemental New Drug Application For Arcutis’ ZORYVE® (roflumilast) cream 0.05% for the treatment of children aged 2 to 5 with mild to moderate atopic dermatitis. Arcutis Biotherapeutics. February 26, 2025. Accessed February 26, 2025. https://www.arcutis.com/u-s-fda-accepts-supplemental-new-drug-application-for-arcutis-zoryve-roflumilast-cream-0-05-for-the-treatment-of-children-aged-2-to-5-with-mild-to-moderate-atopic-dermatitis/.

2. Smith T. Roflumilast Cream 0.05% effective for atopic dermatitis in patients aged 2-5 years. HCP Live. February 24, 2025. Accessed February 26, 2025. https://www.hcplive.com/view/roflumilast-cream-0-05-effective-atopic-dermatitis-patients-aged-2-5-years.

3. Arcutis Announces Publication of Positive Data from INTEGUMENT-PED Trial Evaluating ZORYVE® (roflumilast) Cream 0.05% in Children 2 to 5 Years Old with Mild to Moderate Atopic Dermatitis in Pediatric Dermatology. Arcutis Biotherapeutics, Inc. February 24, 2025. https://www.arcutis.com/arcutis-announces-publication-of-positive-data-from-integument-ped-trial-evaluating-zoryve-roflumilast-cream-0-05-in-children-2-to-5-years-old-with-mild-to-moderate-atopic-dermatitis-in-pediat/.