FDA Accepts sNDA for Roflumilast Cream for AD Patients Ages 2-5

The US Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) for ZORYVE (roflumilast) cream 0.05%, for the topical treatment of mild to moderate atopic dermatitis (AD) in children 2 to 5 years old, Arcutis Biotherapeutics, Inc. announced.

The FDA has set a PDUFA target action date of October 13, 2025, for this application for the once-daily, next generation phosphodiesterase-4 (PDE4) inhibitor.

“In clinical trials, investigational ZORYVE cream 0.05% has shown significant positive results in treating AD 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,” clinical trial investigator Mercedes E. Gonzalez, MD, said in a press release. “In children, AD often occurs on sensitive areas like the face and neck. In addition to persistent itching and scratching, AD 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.” 

Arcutis president and CEO Frank Watanabe noted in the press release that topical treatments prescribed to young AD 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 AD in these very young children, with a safe and tolerable profile that dermatology clinicians trust from their experience with our ZORYVE portfolio,” Watanabe said in the release. “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 AD.”

The sNDA is supported by positive results from the pivotal INTEGUMENT-PED Phase 3 trial (4 weeks), the INTEGUMENT-OLE long-term extension study (up to 52 weeks), as well as a Phase 1 pharmacokinetic study.

INTEGUMENT-PED, the pediatric pivotal vehicle-controlled Phase 3 trial, enrolled 652 children from 2 to 5 years of age, with an AD Body Surface Area (BSA) ranging from 3% to 82% and a mean BSA of 22%. Key trial results include:

·       The data showed significant improvements as early as Week 1. At Week 4, 25.4% of children treated with ZORYVE 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 (P<0.0001).

·       The study also met all pre-determined secondary endpoints, with significant improvements seen across all time points, including vIGA-AD success and vIGA-AD of ‘Clear’ and ‘Almost Clear’ at Week 1. 

·       ZORYVE also helped rapidly reduce the itch, with over a third of the children who had a baseline Worst Itch Numeric Scale (WI-NRS) score ≥4 (as reported by the caregiver) achieving a four-point reduction in WI-NRS at Week 4 (vs. 18.0% for vehicle-treated children [nominal P=0.0002]). 

ZORYVE cream 0.05% was well-tolerated in the studies. Overall, the incidence of adverse events (AEs) in INTEGUMENT-PED was low. The safety profile observed in 2- to 5-year-old pediatric subjects treated with ZORYVE cream 0.05% during the trial was consistent with the favorable safety profile established in adults and older pediatric subjects treated with ZORYVE cream 0.15% with mild to moderate AD.