The FDA assigned the application a PDUFA target action date of July 07, 2024.

The U.S. Food and Drug Administration (FDA) has accepted  Arcutis’ supplemental new drug application (sNDA) for roflumilast cream 0.15% for the treatment of atopic dermatitis (AD) in adults and children down to age 6. 

Roflumilast cream is a once-daily, steroid-free, phosphodiesterase-4 (PDE4) inhibitor. The FDA assigned the application a Prescription Drug User Fee Act (PDUFA) target action date of July 07, 2024.

“In clinical trials, roflumilast cream demonstrated rapid and sustained improvement in the signs and symptoms of disease, as well as long-term proactive disease control with twice weekly maintenance dosing,” says study author Lawrence Eichenfield MD, chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego, professor of dermatology and pediatrics and vice-chair of the Department of Dermatology at UC San Diego School of Medicine, in a news release. “With this profile, patients will not need to make tradeoffs between long-term safety, efficacy, and tolerability. Roflumilast cream if approved, has the potential to simplify the approach to disease control for children and adults.”

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. 

INTEGUMENT-1 and INTEGUMENT 2(The INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis) were two identical Phase 3, parallel group, double blind, vehicle-controlled trials evaluating the safety and efficacy of roflumilast cream 0.15% in AD. 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%, and 28.9% compared to a vehicle rate of 12.0% 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.

In addition, 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%; INTEGUMENT-2: 42.0% vs. 19.7%) with significant results observed as early as Week 1 in both studies.

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%).

“With this filing acceptance, we are one step closer to potentially providing a new topical option for the millions of Americans living with atopic dermatitis. Given the prevalence of this disease in both children and adults, as well as the need for better long-term management, we believe once-daily, steroid-free roflumilast cream has the potential to become the new standard of care in atopic dermatitis,” adds Frank Watanabe, president and chief executive officer at Arcutis. “We look forward to working closely with the FDA during the review process as part of our ongoing efforts to develop topical roflumilast for the treatment of immune-mediated skin diseases.”