Once-daily roflumilast cream 0.05% (Zoryve, Arcutis) showed durable efficacy and favorable safety profile in the treatment of mild to moderate atopic dermatitis (AD) in children 2 to 5 years old, according to results from the INTEGUMENT-OLE long-term open-label study.
Arcutis intends to submit a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration in the first quarter of 2025 for roflumilast cream 0.05% for the treatment of AD in individuals ages 2-5 years. Roflumilast cream 0.15% is approved for the topical treatment of mild to moderate AD in adults and pediatric patients down to age 6.
Efficacy was not only maintained but improved over time, with 71.9% of participants who rolled over from the roflumilast cream 0.05% treatment arm in INTEGUMENT-PED achieving 75% improvement from baseline in Eczema Area and Severity Index (EASI-75) after 56 weeks. Moreover, roflumilast cream was well-tolerated, with no new safety signals observed during treatment of up to 56 weeks in duration.
“When choosing a therapy for very young children, health care providers and caregivers are looking for treatments that provide both rapid relief and are well-tolerated and suitable for long-term use,” says Adelaide Hebert, MD, Professor of Dermatology and Pediatrics at UTHealth Houston in Houston, TX, and INTEGUMENT trial investigator, in a news release. “These results build upon the findings from the Phase 3 trial of roflumilast cream 0.05% that demonstrated rapid efficacy within the first 4 weeks of treatment, and further showed long-term durable efficacy and tolerability of investigational roflumilast cream, with continued improvement over the course of the long-term study.”
In the study, 53.8% of participants who rolled over from the roflumilast cream treatment arm in INTEGUMENT-PED achieved a validated Investigator Global Assessment-Atopic Dermatitis (vIGA-AD) success, defined as vIGA-AD value of 0 or 1 plus a 2-grade improvement from baseline, at 56 weeks.
The long-term study results reinforce the safety and tolerability profile of roflumilast cream 0.05% already seen in the 4-week pivotal INTEGUMENT-PED clinical trial, with no new safety signals observed up to 56 weeks. Overall incidence of adverse events was low, with most being mild to moderate in nature. The most frequently reported adverse events (≥3%) included: upper respiratory tract infection, nasopharyngitis, pyrexia, influenza, COVID-19, and otitis media. Overall, only 3.0% of trial participants discontinued the study due to adverse events.
The “INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis Open Label Extension (INTEGUMENT-OLE) was a Phase 3, multicenter, open-label extension study of the long-term safety of roflumilast cream 0.15% in adults and children ages 6 years and older with AD and roflumilast cream 0.05% in children ages 2 to 5 years. A total of 562 individuals enrolled in the study after completing the INTEGUMENT-PED Phase 3 trial.
The study evaluated monotherapy with roflumilast cream 0.05% with no rescue treatment permitted. Beginning at Week 4 of INTEGUMENT-OLE, any participant who achieved vIGA-AD of ‘0-Clear’ switched to twice weekly maintenance treatment. Participants were able to continue twice weekly maintenance dosing, as long as vIGA-AD remained either ‘0‑Clear’ or ‘1-Almost Clear’. Participants resumed once-daily dosing if vIGA-AD reached ≥2-Mild, and could also resume once-daily dosing if signs/symptoms of AD were not adequately controlled with maintenance therapy.
The primary objective of the study was to assess the long-term safety of roflumilast cream. Secondary endpoints included vIGA-AD score of 0 or 1 at each assessment, vIGA-AD success defined as vIGA-AD value of 0 or 1 plus a 2-grade improvement from baseline, and Eczema Area and Severity Index (EASI) score over time. The assessment of vIGA-AD Success and EASI-75 response, as reported here, references baseline of INTEGUMENT-PED.
