FDA Approves Roflumilast (Zoryve) Cream 0.05% for Atopic Dermatitis in Children Aged 2-5 Years

The US Food and Drug Administration has approved Arcutis Biotherapeutics’ supplemental new drug application (sNDA) for roflumilast (Zoryve) cream 0.05% for the topical treatment of mild to moderate atopic dermatitis in children 2-5 years of age.1

As described in an October 6, 2025, press release from the Company, the approval is based on data from the INTEGUMENT-PED phase 3 trial, the INTEGUMENT-OLE long-term extension study, and a phase 1 pharmacokinetic study, representing the 6th FDA approval for the roflumilast portfolio in just over 3 years.1,2

“It is essential to have safe and effective treatments for children, who are often diagnosed with atopic dermatitis at a young age and can live with the condition across their lifetime. Young children often experience widespread disease, affecting large portions of their skin. Although topical steroids have been the standard treatment for years, they are not appropriate for long-term use,” Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego and INTEGUMENT study investigator, said in a statement.1 "In clinical trials, [roflumilast] cream 0.05% rapidly improved the severity and extent of eczema (atopic dermatitis) signs and symptoms, with approximately 40% of children achieving a 75% improvement from baseline as measured by EASI, and more than one-third (35%) achieving a clinically meaningful improvement in itch intensity, both in only four weeks. With this approval, healthcare providers and families have an effective new treatment option for young children with atopic dermatitis.”

An advanced topical phosphodiesterase 4 (PDE4) inhibitor, roflumilast boasts several FDA indications. Roflumilast topical foam 0.3% is approved by the FDA for the treatment of plaque psoriasis of the scalp and body in patients 12 years of age and older, as well as for seborrheic dermatitis in patients 9 years of age and older. Roflumilast cream, 0.15%, is indicated for topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 6 years of age and older.1

The latest approval of roflumilast cream 0.05% was based on clinical trial data from from the INTEGUMENT-PED trial, the INTEGUMENT-OLE long-term extension study, and a phase 1 pharmacokinetic study demonstrating rapid clearance of atopic dermatitis with roflumilast treatment, with positive results across all efficacy endpoints, and was safe and well tolerated.1

INTEGUMENT-PED was a randomized, double-blind, vehicle-controlled, parallel-group study, that evaluated roflumilast cream or vehicle once-daily for 4 weeks in 652 children 2-5 years of age (n = 437 treated with roflumilast cream, n = 215 vehicle). INTEGUMENT-OLE was a phase 3, multicenter, open-label extension study of the long-term safety and efficacy of roflumilast cream 0.15% in adults and children ≥ 6 years of age with atopic dermatitis and roflumilast cream 0.05% in children ages 2-5 years with atopic dermatitis. A total of 658 children and adults from INTEGUMENT-1 and -2 and 562 children from INTEGUMENT-PED enrolled in the INTEGUMENT-OLE study.1,3

In INTEGUMENT-PED, roflumilast demonstrated rapid disease clearance, with data showing significant improvements as early as Week 1. At Week 4, results showed 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 <.0001).1,3

The study also met all pre-determined secondary endpoints, with improvements seen across all time points, including vIGA-AD of ‘Clear’ and ‘Almost Clear’ at Week 1. Additionally, 39.4% of children using roflumilast cream achieved a 75% reduction in Eczema Area and Severity Index (EASI-75) at Week 4 compared to 20% using vehicle, with differences observed as early as Week 1.1,3

In INTEGUMENT-OLE, roflumilast treatment continued for up to 56 weeks. Results showed efficacy was maintained over time and continued to improve, with 71.9% of participants who rolled over from the roflumilast cream 0.05% treatment arm in the INTEGUMENT-PED trial achieving 75% improvement from baseline in EASI after 56 weeks of treatment.1

Starting at Week 4 of INTEGUMENT-OLE, participants who achieved a vIGA-AD score of Clear (0), switched to proactive twice-weekly application (170 participants; 30.2% of those treated with roflumilast cream 0.05%). For participants who switched to twice-weekly application, the median duration of disease control (maintaining vIGA-AD of ‘Clear’ or ‘Almost Clear’, with adequate control of signs and symptoms on the twice-weekly schedule application) was 238 days (34 weeks), consistent with the 281 days observed for adults and children down to age 6 who used twice-weekly dosing with roflumilast cream 0.15%.1

“[Roflumilast] cream was intentionally formulated to address the critical unmet need in atopic dermatitis care, and it provides a safe, effective alternative to steroid treatments, targeting the underlying inflammation that drives disease activity. Notably, [roflumilast] does not include ingredients known to compromise the skin barrier, which is especially important for young children with atopic dermatitis,” Frank Watanabe, president and chief executive officer of Arcutis, said in a statement.1 “[Roflumilast] provides patients and their families with a treatment option for long-term, continuous use, helping maintain clear skin and limiting cumulative topical steroid exposure.”

As described in the press release, Arcutis intends to make roflumilast cream 0.05% widely available via key wholesaler and pharmacy channels as a new treatment option by the end of October 2025.1

References

1. Arcutis Biotherapeutics. FDA Approves Arcutis’ ZORYVE® (roflumilast) Cream 0.05% for the Treatment of Atopic Dermatitis in Children Ages 2 to 5. October 6, 2025. Accessed October 6, 2025. https://investors.arcutis.com/news-releases/news-release-details/fda-approves-arcutis-zoryver-roflumilast-cream-005-treatment

2. Campbell P. FDA Accepts Roflumilast Cream sNDA in Atopic Dermatitis for Ages 2-5 Years. February 26, 2025. Accessed October 6, 2025. https://www.hcplive.com/view/fda-accepts-roflumilast-cream-snda-in-atopic-dermatitis-for-ages-2-5-years

3. Smith T. Roflumilast Cream 0.05% effective for atopic dermatitis in patients aged 2-5 years. HCP Live. February 24, 2025. Accessed October 6, 2025. https://www.hcplive.com/view/roflumilast-cream-0-05-effective-atopic-dermatitis-patients-aged-2-5-years