The FDA has accepted the supplemental new drug application (sNDA) from Arcutis Biotherapeutics, Inc. for roflumilast cream 0.15% for the treatment of atopic dermatitis (AD) in adults and children down to age 6. The FDA assigned the application a Prescription Drug User Fee Act (PDUFA) target action date of July 07, 2024.
Roflumilast cream, a once-daily, steroid-free, phosphodiesterase-4 (PDE4) inhibitor, topical treatment of plaque psoriasis, including intertriginous areas, in patients 6 years of age and older as a 0.3% cream (Zoryze®). Roflumilast cream for AD was evaluated at lower doses of 0.15% for adults and children 6 years of age and older and 0.05% for children aged 2 to 5 years.
The sNDA is supported by positive results from three Phase 3 programs as well as a Phase 2 dose ranging study, and two Phase 1 pharmacokinetic studies. Two identical Phase 3, parallel group, double blind, vehicle-controlled trials, INTEGUMENT-1 and INTEGUMENT-2 (The INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis), evaluated the safety and efficacy of roflumilast cream 0.15% in AD. Arcutis reports that roflumilast met its primary endpoint with a validated Investigator Global Assessment – Atopic Dermatitis (vIGA-AD) Success rate of 32.0% compared to a vehicle rate of 15.2% (P<0.0001), and 28.9% compared to a vehicle rate of 12.0% (P<0.0001) at Week 4, in INTEGUMENT-1 and -2, respectively.
More than 30% of individuals treated with roflumilast cream in each study achieved Worst Itch-Numeric Rating Scale (WI-NRS) Success at Week 4, with rapid and significant improvements observed as early as 24 hours following the first application.
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. 22.0%, P<0.0001; INTEGUMENT-2: 42.0% vs. 19.7%, P<0.0001) with significant results observed as early as Week 1 in both studies (nominal P=0.0006; nominal P=0.0329).
Roflumilast cream 0.15% was well tolerated. The incidence of Treatment Emergent Adverse Events (TEAEs) was low in both active treatment and vehicle arms, with most TEAEs assessed as mild to moderate in severity. There were no adverse reactions in the combined Phase 3 pivotal trials that occurred in more than 2.9% of subjects in either arm. The most common adverse reactions included headache (2.9%), nausea (1.9%), application site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%).