FDA Approves Zoryve (roflumilast) cream 0.05% for the teatment of aopic dermatitis in children aged 2 to 5 – Arcutis Biotherapeutics

Arcutis Biotherapeutics, Inc. announced that the FDA has approved the supplemental new drug application (sNDA) for Zoryve  (roflumilast) cream 0.05% for the topical treatment of mild to moderate atopic dermatitis in children 2 to 5 years of age. Once-daily  Zoryve  cream 0.05% provides rapid and significant clearance of atopic dermatitis anywhere on the body and offers clinicians, parents, and caregivers of children ages 2 to 5 an alternative to steroids that can be used for any duration.

The FDA approval is based on results from the INTEGUMENT-PED Phase III trial (INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis), the INTEGUMENT-OLE long-term extension study and a Phase I pharmacokinetic study. In clinical trials ,Zoryve demonstrated rapid clearance of atopic dermatitis, with positive results across all efficacy endpoints, and was safe and well tolerated.

INTEGUMENT-PED was a randomized, double-blind, vehicle-controlled, parallel-group study, that evaluated Zoryve cream or vehicle once-daily for 4 weeks in 652 children ages 2 to 5 years (n=437 treated with Zoryve cream, n=215 vehicle). INTEGUMENT-OLE was a Phase III, multicenter, open-label extension study of the long-term safety and efficacy of Zoryve cream 0.15% in adults and children ages 6 years and older with atopic dermatitis and Zoryve cream 0.05% in children ages 2 to 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.

In the INTEGUMENT-PED trial, Zoryve demonstrated rapid disease clearance, with data showing 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 improvements seen across all time points, including vIGA-AD of ‘Clear’ and ‘Almost Clear’ at Week 1. Additionally, 39.4% of children using Zoryve 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 (exploratory endpoint).

Zoryve was also shown to reduce itch at Week 4, with some caregivers reporting less itching within 24 hours after first application. In an exploratory analysis, over one-third of the children 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% for vehicle-treated children [nominal P=0.0002]).

Zoryve cream 0.05% was well-tolerated in the pivotal studies. The most common adverse reactions reported in the clinical trials of Zoryve cream 0.05% were upper respiratory tract infection, diarrhea, vomiting, rhinitis, conjunctivitis, and headache.

In INTEGUMENT-OLE, Zoryve treatment continued for up to 56 weeks. Not only was efficacy maintained over time, but it continued to improve, with 71.9% of participants who rolled over from the Zoryve cream 0.05% treatment arm in the INTEGUMENT-PED trial achieving 75% improvement from baseline in EASI after 56 weeks of treatment.

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 Zoryve 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 Zoryve cream 0.15%.

The safety profile of Zoryve cream 0.05% was generally consistent with continued treatment in INTEGUMENT-OLE.

“ZORYVE 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, ZORYVE does not include ingredients known to compromise the skin barrier, which is especially important for young children with atopic dermatitis,” said Frank Watanabe, president and chief executive officer of Arcutis. “ZORYVE provides patients and their families with a treatment option for long-term, continuous use, helping maintain clear skin and limiting cumulative topical steroid exposure.”

“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,” said Lawrence F. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego and INTEGUMENT study investigator. “In clinical trials, ZORYVE 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.”