Roflumilast Cream 0.15% Approved for Treatment of Atopic Dermatitis in People Aged 6 Years and Older

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Arcutis Biotherapeutics announced this week approval by the US FDA of the company’s supplemental new drug application (sNDA) for roflumilast cream 0.15% (Zoryve) for the treatment of mild-to-moderate atopic dermatitis (AD) in adults and children as young as age 6 years. The steroid-free topical is applied once daily and has been developed specifically for long-term disease control, according to an Arcutis news release. Arcutis expects the product to be available by the end of July.

“People suffering from AD experience intense itch, rash, and sensitive skin, which warrant effective, safe, and well-tolerated treatments,” Jonathan Silverberg, MD, PhD, MPH, professor of dermatology, and the director of clinical research and director of contact dermatitis at The George Washington University School of Medicine and Health Sciences in Washington, DC,” said in the Arcutis statement. “ZORYVE was developed with the AD patient in mind, to deliver the drug in a moisturizing vehicle that is formulated without common sensitizers or irritants and does not further disrupt the abnormal skin barrier. It’s also important to note that in clinical trials ZORYVE monotherapy provided safe and effective long-term disease control to AD patients.”

AD is a chronic condition and the instability of the disease can make individuals feel as though they “are constantly chasing their AD flares,” Lawrence F Eichenfield, MD, professor of dermatology and pediatrics and vice chair of the department of dermatology at UC San Diego School of Medicine, said in the release. Eichenfield, an investigator for the INTEGUMENT clinical trial program of roflumilast cream 0.15% in AD, emphasized the rapid improvement in itch observed with the cream, stating that pruritis is the most bothersome reported disease symptom. “In clinical trials, 9 in 10 patients saw some improvement at 4 weeks, with 69% of patients demonstrating a clinically meaningful improvement" of at least 50% in eczema area and severity index (EASI) score.

Roflumilast is a “next-generation” topical phosphodiesterase 4 (PDE4) inhibitor. PDE4 inhibitors can have a direct effect on itch-signaling nerves of the skin, as well as on the inflammatory pathways.

INTEGUMENT Development Program

The FDA based its approval of the Arcutis sNDA on positive results from the 3 phase 3 INTEGUMENT registration trials, a phase 2 dose-ranging study, and two phase 1 pharmacokinetic studies. INTEGUMENT-1 (NCT04773600) and INTEGUMENT-2 (NCT04773600) were identical, parallel-group, double-blind, vehicle-controlled, trials that evaluated the safety and efficacy of roflumilast cream 0.15% or vehicle applied once-daily to affected skin for 4 weeks. The studies enrolled 1337 adults and children aged 6 years and older with mild to moderate AD.

Both studies met the shared primary endpoint, a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of clear (0) or almost clear (1) and a 2-grade improvement from baseline at week 4 (INTEGUMENT-1: 32.0% roflumilast cream vs 15.2% vehicle) and INTEGUMENT-2: 28.9% roflumilast cream vs 12.0% vehicle) (P <.001 for both). In both studies, 40% of all participants treated with roflumilast cream achieved a vIGA-AD score of 0 or 1 at week 4, with significant improvement seen as early as week 1 (P <.001 for all).

Within 24 hours of the first application, participants treated with roflumilast reported significant improvement in pruritis as measured by change from baseline in scores on the Worst-Itch-Numeric Rating Scale (WI-NRS) compared with vehicle-treated participants. Moreover, nearly one-third (more than 30%) of treated participants in both phase 3 trials achieved WI-NRS “success” after 4 weeks, defined a at least a 4-point reduction on the 0 to 10 scale (P < .01).

The incidence of treatment emergent adverse events was low in both active treatment groups and vehicle arms, most reported as mild to moderate in severity.

Roflumilast cream 0.15% was also evaluated in the INTEGUMENT open label extension (OLE) study, which enrolled 658 participants rolled over from either of the phase 3 trials. At any time after 4 weeks of once-daily application a participant reached a vIGA-AD score of clear (0), they were switched to twice-weekly application (130 participants; 19.8% of study population). All other participants continued once-daily application. Overall, 61.5% and 66.2% of patients who rolled over from the roflumilast cream arm in INTEGUMENT-1 or INTEGUMENT -2 demonstrated EASI 75 after 28 weeks and 56 weeks, respectively.

“Topical steroids have been the foundation of treatment for AD for the past 50 years. Having a new and effective steroid-free option, without some of the risks associated with topical and systemic steroids, is a welcome advancement for dermatologists, patients, and caregivers,” investigator Eichenfield said.

Roflumilast cream for AD is currently being evaluated at a lower dose of 0.05% for children aged 2 to 5 years, according to Arcutis. The company also has completed its clinical development program for roflumilast foam 0.3% for the treatment of scalp and body psoriasis and intends to submit an sNDA in the third quarter of 2024.

Source: FDA approves Arcutis’ ZORYVE (roflumilast) cream 0.15% for the treatment of atopic dermatitis in adults and children down to 6 years of age. News release. Arcutis Biotherapeutics. July 9, 2024. Accessed July 9, 2024. https://investors.arcutis.com/news-releases/news-release-details/fda-approves-arcutis-zoryver-roflumilast-cream-015-treatment