Promising and Consistent Topline Results Seen in Phase 3 Trial of Roflumilast in AD

Fully 28.9 percent of individuals treated with roflumilast cream 0.15% achieved Investigator Global Assessment Success compared to 12.0% of individuals treated with vehicle.

Arcutis Biotherapeutics, Inc.’s roflumilast met the key primary and secondary endpoints in the INTEGUMENT-2 pivotal Phase 3 trial of , adults and children 6 years and older with mild to moderate atopic dermatitis (AD).

The new findings are consistent with positive topline results from the INTEGUMENT-1 trial released in November 2022, the Company reports.

Roflumilast cream 0.15% is  a once-daily, non-steroidal topical phosphodiesterase-4 (PDE4) inhibitor,

The study met its primary endpoint, with 28.9 percent of individuals treated with roflumilast cream 0.15% achieving IGA Success, defined as a validated Investigator Global Assessment – Atopic Dermatitis (vIGA-AD) score of ‘clear’ or ‘almost clear’ plus a 2-grade improvement from baseline at Week 4, compared to 12.0 percent of individuals treated with vehicle, the study showed.

“Atopic dermatitis, a common condition in children through adults, is a chronic disease characterized by intense, persistent itching and eczematous rashes, that can greatly impact quality of life,” explains Lawrence F. 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, and study investigator, in a news release. “Adults and children who suffer with atopic dermatitis are in need of non-steroidal topical treatment options that are safe, well-tolerated, and suitable for long-term use. The strong results from this second pivotal Phase 3 trial, which are consistent with the findings from INTEGUMENT-1, further reinforce the safety and efficacy profile of roflumilast cream and its potential as a new treatment option for atopic dermatitis.”

Roflumilast cream also demonstrated rapid and statistically significant improvements compared to vehicle on key secondary endpoints, including 42.0 percent of individuals treated with roflumilast cream 0.15% achieving a 75 percent improvement in Eczema Area and Severity Index (EASI-75) at Week 4 compared to 19.7 percent treated with vehicle,

In an additional secondary endpoint, the study evaluated reduction in itch in individuals 12 years of age and older, with 30.2 percent of individuals treated with roflumilast cream achieving a 4-point reduction in Worst Itch Numeric Scale (WI-NRS) at Week 4 versus 12.4 percent for vehicle-treated subjects.

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 severity. Overall, incidence of adverse events were low, with no adverse event occurring in more than 3.5 percent of subjects in either arm. The most frequent adverse events in the roflumilast arm (≥1%) included headache, nausea, vomiting, diarrhea, and upper respiratory tract infection. More than 90 percent of patients who were randomized to roflumilast cream in the study completed the full four weeks, and there were few discontinuations due to adverse events (1.8% and 0.9% in the roflumilast cream and vehicle groups, respectively).

“We are very pleased with these positive findings from INTEGUMENT-2, our second of two Phase 3 pivotal trials with roflumilast cream 0.15% in individuals with mild to moderate atopic dermatitis aged 6 years and older. Roflumilast cream delivered positive efficacy as early as Week 1 for symptomatic response in itch and Week 2 for IGA Success, as well as favorable safety and tolerability results,” says Patrick Burnett, MD, PhD, FAAD, chief medical officer at Arcutis. “With these positive results, we plan to move forward with filing a supplemental new drug application (sNDA) with the United States Food & Drug Administration (FDA) for roflumilast cream 0.15% for the treatment of mild to moderate atopic dermatitis in adults and children 6 years of age and older in the second half of 2023.

“I am incredibly proud of the entire Arcutis team for their ability to complete enrollment and report positive results for four Phase 3 pivotal trials across three indications for topical roflumilast in 2022. All of this is on the heels of the FDA approval and successful launch of our first product in plaque psoriasis,” adds Frank Watanabe, president and CEO at Arcutis. “We are also deeply grateful for all of the investigators and individuals with atopic dermatitis, seborrheic dermatitis, and scalp and body psoriasis who volunteered to enroll in these trials.”

Summary of Topline Results from INTEGUMENT-1 and INTEGUMENT-2
Arcutis investigated roflumilast cream 0.15% in adults and children aged 6 and over with mild to moderate AD in two identical pivotal Phase 3 studies, INTEGUMENT-1 and INTEGUMENT-2. In November, the company reported positive topline findings from INTEGUMENT-1.

About INTEGUMENT-2

The “INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis” 2 (INTEGUMENT-2) is a Phase 3, parallel group, double blind, vehicle-controlled trial in which roflumilast cream 0.15% or vehicle is applied once daily for four weeks to individuals 6 years of age and older with mild to moderate AD involving ≥3% body surface area. A total of 683 individuals were randomized in the study. The primary endpoint was IGA Success, defined as vIGA-AD score of ‘clear’ or ‘almost clear’ plus a 2-grade improvement from baseline at Week 4. Multiple secondary endpoints were also evaluated, including itch as measured by WI-NRS as well as the proportion of subjects who attained at least a 75% improvement in EASI-75 at Week 4.

After completing INTEGUMENT-1 and INTEGUMENT-2, individuals were eligible to enroll in an open-label extension study (INTEGUMENT-OLE) evaluating treatment with once-daily roflumilast cream 0.15% for up to 12 months.

Arcutis is enrolling a third pivotal Phase 3 trial, the “INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis in PEDiatric patients” (INTEGUMENT-PED) to evaluate roflumilast cream 0.05% in children 2 to 5 years of age with mild to moderate AD. The Company plans to report topline data from this study in 2023.