Positive long-term results of roflumilast cream 0.15% showing durable and improved efficacy over time and favorable safety profile in treatment of mild to moderate atopic dermatitis (AD)

In the study, roflumilast cream was well-tolerated, with no new safety signals observed during treatment up to 56 weeks in duration.

Efficacy was not only maintained but improved over time, with 46.1% and 51.0% of participants who rolled over from the roflumilast cream treatment arm in INTEGUMENT-1 or -2 achieving 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 Weeks 28 and 56, respectively. Starting at Week 4 of INTEGUMENT-OLE, participants who achieved a vIGA-AD score of clear (0) switched to twice weekly maintenance dosing. Participants were to resume once-daily dosing if vIGA-AD reached mild or if signs or symptoms were not adequately controlled. Over two-thirds of participants who switched to maintenance dosing remained on the twice weekly schedule for more than half of their time in the study (post-Week 4).

“When determining a treatment plan for an adult or child with a chronic, burdensome skin condition such as atopic dermatitis, long-term efficacy and safety are both incredibly important considerations,” said Eric Simpson, MD, MCR, FAAD, Professor of Dermatology at Oregon Health & Science University in Portland, Oregon, and INTEGUMENT trial investigator. “These results build upon the positive findings from the pivotal Phase III trials of roflumilast cream 0.15% in atopic dermatitis demonstrating rapid efficacy within the first 4 weeks of treatment, and further validate the long-term durable efficacy and tolerability of roflumilast cream, with continued improvement over the course of the long-term study. Importantly, individuals who reached clear were able to switch to a twice weekly dosing and maintain control of their disease through this schedule.”

“The goal and greatest clinical challenge for treating adults and children with atopic dermatitis is dependable disease control. Due to the instability of this chronic disease, long-term control and safety is key; however, data on prevention and maintenance with topical therapy is lacking. This long-term study was designed to study proactive treatment, for patients with clear skin, to optimize and maintain control with twice weekly dosing,” said Emma Guttman-Yassky, MD, PhD, System Chair of the Department of Dermatology and Waldman Professor of Dermatology and Immunology at the Icahn School of Medicine at Mount Sinai. “These study results provide evidence for a paradigm shift to break the cycle of the current topical paradigm that only reactively chase and manage flares, showing the utility of infrequent preventive treatment regimens to disease control.” Dr. Guttman is a paid consultant with Arcutis Biotherapeutics, Inc.

Additionally, in the study, 61.5% and 66.2% of participants who rolled over from the roflumilast cream arm in INTEGUMENT-1 or -2 demonstrated a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75) after 28 weeks and 56 weeks, respectively.

The long-term study results reinforce the safety profile of roflumilast cream already seen in the short-term INTEGUMENT-1 and INTEGUMENT-2 clinical trials, 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 ( greater than 2%) included: COVID-19, upper respiratory tract infection, nasopharyngitis, and headache. Overall, only 3.0% of trial participants discontinued the study due to adverse events.

Roflumilast cream is uniquely formulated to deliver treatment without sensitizing excipients and irritants, which can often disrupt the skin barrier. We are excited by these results, which demonstrate the long-term efficacy and the safety and tolerability profile of our next generation phosphodiesterase type 4 (PDE4) inhibitor for the treatment of atopic dermatitis,” said Patrick Burnett, MD, PhD, FAAD, chief medical officer at Arcutis. “Based on the positive results we have seen, we are convinced that, if approved, roflumilast cream will provide individuals with atopic dermatitis with an important new long-term treatment option that is designed with their specific needs in mind.”

Arcutis intends to submit a supplemental New Drug Application (sNDA) late in the third quarter of 2023 for roflumilast cream 0.15% for the treatment of mild to moderate atopic dermatitis in individuals ages 6 years and older.