Takeaways
- The FDA has accepted the supplemental New Drug Application (sNDA) for roflumilast cream 0.15% to treat atopic dermatitis (AD) in children and adults aged 6 and up.
- Roflumilast is a once-daily, steroid-free, phosphodiesterase-4 (PDE4) inhibitor, with a Prescription Drug User Fee Act (PDUFA) date set for July 7, 2024.
- Positive results from two phase 3 trials, INTEGUMENT-1 and INTEGUMENT-2, supported the sNDA acceptance, demonstrating efficacy and safety.
- Roflumilast cream achieved primary outcomes, including a significant improvement in Investigator Global Assessment–Atopic Dermatitis (vIGA-AD) scores.
- More than 40% of individuals treated with roflumilast cream achieved a 75% reduction in Eczema Area and Severity Index (EASI-75) at week 4 compared to the vehicle.
The FDA has accepted a supplemental New Drug Application (sNDA) for roflumilast cream 0.15% (Arcutis Biotherapeutics) to treat atopic dermatitis (AD) in children and adults 6 years and up.1
The once-daily, steroid-free, phosphodiesterase-4 (PDE4) inhibitor has been assigned a Prescription Drug User Fee Act (PDUFA) date of July 7, 2024, according to the manufacturer.1 The sNDA for roflumilast 0.15% was filed with the FDA on September 12, 2023.2
“AD is a complex disease and there's this incredible range in severity of AD and while we have incredible new systemic medicines to help us with our more severe patients, most patients still will be using topical therapy, and many of them can be effectively managed with topical therapies,” said Lawrence Eichenfield, MD, professor of dermatology and pediatrics, vice chair, Department of Dermatology, chief, Pediatric and Adolescent Dermatology, University of California, San Diego, and Rady Children’s Hospital, San Diego, in an interview with Contemporary Pediatrics.
He added, “But we've had some needs in regard to that because there is still incredible concern about topical corticosteroids. You can't use them for extended periods of time, there's unfortunately, I'd say even more concern about topical corticosteroids being fed by social media that is making people think that exacerbations of their eczema may be due to the topical steroids, where it could just be the natural disease, not to take away that some individuals truly can have a steroid withdrawal phenomenon.”
Eichenfield said newer agents that bring safety and efficacy to patients is important, especially when they can be approved down to younger ages.
The acceptance of the sNDA is supported by positive results from 2 phase 3 trials, INTEGUMENT-1 (NCT04773587) and INTEGUMENT-2 (NCT04773600). The studies were identical, phase 3, double-blind, parallel-group, and vehicle-controlled clinical trials.1,2
Participants, 6 years or older with mild to moderate AD involving 3% or more body surface area, were treated with roflumilast cream 0.15% or vehicle once a day for 4 weeks.2
Roflumilast met its primary outcome of an Investigator Global Assessment–Atopic Dermatitis (vIGA-AD) score of clear (0) or almost clear (1), plus a 2-grade improvement from baseline at week 4 (INTEGUMENT-1: 32% roflumilast cream vs 15.2% vehicle [P < 0.0001]) and (INTEGUMENT-2: 28.9% roflumilast cream vs 12% vehicle [P < 0.0001]).2
In each study, over 30% of individuals treated with roflumilast cream achieved a Worst Itch-Numeric Rating Scale (WI-NRS) success at week 4, demonstrating “significant” improvements that were observed as early as 24 hours after the first application.1
More than 40% of children and adults treated with roflumilast cream achieved a 75% reduction in Eczema Area and Severity Index (EASI-75) at week 4 compared to vehicle (INTEGUMENT-1: 43.2% vs 22% [P < 0.0001]; INTEGUMENT-2: 42.0% VS 19.7% [P < 0.0001]).1
Significant results were observed as early as week 1 in both studies, according to Arcutis (nominal P = 0.0006; nominal P = 0.0329).1
The incidence of Treatment Emergent Adverse Events (TEAEs) was low in both arms, with most assessed as “mild to moderate” in severity. There were no adverse reactions in the combined phase 3 trials that occurred in more than 2.9% of subjects in either the active treatment or vehicle arm.1
“The announcement of the FDA accepting the sNDA for roflumilast [0.15%], plus other work with that drug and other drugs, with different formulations and different agents, I think will be very important going forward to have a newer set of nonsteroidal medicines for AD,” Eichenfield said.
Roflumilast 0.3% (ZORYVE; Arcutis) is FDA approved for the topical treatment of plaque psoriasis in patients aged 6 years and up.1 Roflumilast cream was also evaluated at lower dose, including for 0.05% for children aged 2 to 5 years with AD.1,3
Arcutis plans to submit a sNDA with the FDA for roflumilast 0.05%.3
References:
- FDA accepts Arcutis’ supplemental New Drug Application for roflumilast cream 0.15% for the treatment of atopic dermatitis in adults and children down to age 6. Arcutis Biotherapeutics. Press release. November 29, 2023. Accessed November 29, 2023. https://investors.arcutis.com/news-releases/news-release-details/fda-accepts-arcutis-supplemental-new-drug-application
- Fitch, J. Arcutis submits roflumilast 0.15% sNDA for AD in children 6 years and up. Contemporary Pediatrics. September 21, 2023. Accessed November 29, 2023. https://www.contemporarypediatrics.com/view/arcutis-submits-roflumilast-0-15-snda-for-ad-in-children-6-years-and-up
- Fitch, J. Roflumilast cream 0.05% safe, effective for children aged 2 to 5 years with atopic dermatitis. Contemporary Pediatrics. September 20, 2023. Accessed November 29, 2023. https://www.contemporarypediatrics.com/view/roflumilast-cream-0-05-safe-effective-for-children-aged-2-to-5-years-with-atopic-dermatitis
