Arcutis intends to submit a 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.

Roflumilast cream 0.15% showed durable and improved efficacy over time and a favorable safety profile in mild to moderate Atopic Dermatitis (AD), according to interim results from the INTEGUMENT-OLE long-term open-label study.

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.

Fully 46.1% and 51.0% of patients who rolled over from the roflumilast cream treatment arm in INTEGUMENT-1 or -2 achieved 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. In addition, Roflumilast cream maintained disease control even when participants switched to twice weekly maintenance dosing schedule. Long-term safety and tolerability profile was consistent with short-term data in AD, with no new safety signals observed during 56 weeks of treatment, Arcutis reports.

Starting at week four 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 (2) or if signs or symptoms were not adequately controlled. More than 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,” says Eric Simpson, MD, MCR, FAAD, Professor of Dermatology at Oregon Health & Science University in Portland, Oregon, and INTEGUMENT trial investigator. In a news release. “These results build upon the positive findings from the pivotal Phase 3 trials of roflumilast cream 0.15% in atopic dermatitis demonstrating rapid efficacy within the first four 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,” adds 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 (≥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,” says 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.”

About INTEGUMENT-OLE

The “INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis Open Label Extension” (INTEGUMENT-OLE) was a Phase 3, multicenter, open-label extension study of the long-term safety of roflumilast cream 0.15% in adults and children ages 6 years and older with atopic dermatitis and roflumilast cream 0.05% in children ages 2 to 5 years. Individuals completing the INTEGUMENT-1 or INTEGUMENT-2 Phase 3 trials were eligible to enroll (n=658) for either 24 or 52 weeks.

The study evaluated monotherapy with roflumilast cream with no rescue treatment permitted. Beginning at Week 4 of INTEGUMENT-OLE, any participant who achieved vIGA-AD of ‘0-Clear’ switched to twice weekly maintenance treatment. Participants were able to continue twice weekly maintenance dosing, as long as vIGA-AD remained either ‘0‑Clear’ or ‘1-Almost Clear’. Participants resumed once-daily dosing if vIGA-AD reached ≥2-Mild, and could also resume once-daily dosing if signs/symptoms of AD were not adequately controlled with maintenance therapy despite remaining at vIGA-AD of ‘1-Almost Clear’.

The primary objective of the study was to assess the long-term safety of roflumilast cream after either 24 or 52 weeks of treatment. Secondary endpoints include vIGA-AD score of 0 or 1 at each assessment, vIGA-AD success defined as vIGA-AD value of 0 or 1 plus a 2-grade improvement from baseline, Worst Itch Numeric Scale (WI-NRS) score over time, and Eczema Area and Severity Index (EASI) score over time. The assessment of IGA Success and EASI-75 response, as reported here, references baseline of INTEGUMENT-1 and -2.