Arcutis Submits sNDA for Roflumilast for Children 2 to 5 with AD

Arcutis Biotherapeutics, Inc. announced the submission of a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) for roflumilast (ZORYVE) cream 0.05%, a once-daily, next-generation phosphodiesterase 4 (PDE4) inhibitor, for the topical treatment of mild-to-moderate atopic dermatitis (AD) in children 2 to 5 years old.

“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. Data from the pivotal trial demonstrated that roflumilast cream 0.05% provided consistent and rapid relief, and was well-tolerated,” Rocco Serrao, MD, FAAD, an investigator in clinical trials of roflumilast, said in a press release. “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 AD.”

Arcutis president and CEO Frank Watanabe said parents, caregivers, and healthcare professionals need to feel confident in their treatment plan for AD.

“Our clinical development program for ZORYVE reinforces the well-established efficacy, safety, and tolerability profile of roflumilast cream, which was designed to deliver drug without disrupting the skin barrier or using sensitizing excipients and irritants. 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,” Frank Watanabe said in the press release. “We look forward to the opportunity to offer ZORYVE cream 0.05%, if approved, as a new topical therapy for the 1.8 million children between the ages of 2 to 5 with AD and their families.”

The sNDA is supported by positive results from one pivotal Phase 3 trial, one pivotal long-term extension study, as well as a Phase 1 pharmacokinetic study. The INTEGUMENT-PED vehicle-controlled, pivotal Phase 3 trial enrolled 652 children 2 to 5 years of age, with a mean AD Body Surface Area (BSA) of 22% overall, and ranging from 3% to 82%. In the study, at Week 4, 25.4% of children treated with roflumilast 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), with significant improvements seen as early as Week 1. All secondary endpoints were also met, with significant improvements seen across all time points, including vIGA-AD success and vIGA-AD of ‘Clear’ and ‘Almost Clear’ at Week 1. In addition, 35.3% of children treated with roflumilast cream who had a baseline Worst Itch Numeric Scale (WI-NRS) score ≥4 (as reported by the caregiver) achieved a four-point reduction in WI-NRS at Week 4 (vs. 18.0% for vehicle-treated children [nominal P=0.0002]).

Roflumilast cream 0.05% was well-tolerated. Overall, 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. The most frequent adverse events occurring in the roflumilast arm greater than vehicle (≥2%) included upper respiratory tract infection, diarrhea, and vomiting.

The submission is also supported by data from the INTEGUMENT-OLE open-label extension study in which patients ages 2 to 5 (n = 562) were treated for up to 52 weeks.