Late-Breaker: Roflumilast Cream 0.15% Demonstrates Continued Improvement in AD Symptoms Through 56 Weeks

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Late-breaking data presented at the Revolutionizing Alopecia Areata, Vitiligo, and Eczema Conference showed that Arcutis Biotherapeutics’ roflumilast cream 0.15% demonstrated continued improvements in the signs and symptoms of atopic dermatitis, including itch, through 56 weeks in patients aged 6 years and older. The late-breaking data from the INTEGUMENT-OLE long-term, open-label study of investigational once-daily roflumilast cream 0.15% also showed that roflumilast was well-tolerated with no new safety signals observed.¹

The FDA accepted Arcutis’ supplement new drug application for roflumilast cream 0.15% for atopic dermatitis in November 2023. The FDA set a Prescription Drug User Fee Act (PDUFA) target action date of July 7, 2024.²

In INTEGUMENT-OLE, efficacy was maintained over time and continued to improve, with 56.6% of patients who continued to use roflumilast cream from the initial trial and 53.8% of patients who switched to roflumilast cream 0.15% from vehicle after the initial trial achieving validated Investigator Global Assessment-Atopic Dermatitis (vIGA-AD) success, defined asvIGA-AD value of 0 or 1 plus a 2-grade improvement from baseline, at week 56.

Beginning at week 4 of INTEGUMENT-OLE, patients who achieved a vIGA-AD score of clear switched to proactive twice-weekly application (n=130; 19.8% of study population). With these patients, after their first switch to twice-weekly application, the median duration of disease control, defined as maintaining vIGA-AD of 0 or 1 with adequate control of signs and symptoms on the twice-weekly schedule application, was 281 days. Overall,57.7% of patients maintained disease control on the twice-weekly schedule through the final study day.

“I'm really excited to present the open-label extension period of topical roflumilast, 0.15% cream for atopic dermatitis. We know from INTEGUMENT-1 and INTEGUMENT-2, which were both 4-week studies that topical roflumilast 0.15% cream is more effective than the vehicle. But, what the long-term extension study looked at was safety as the primary endpoint, but it also looked at a maintenance dose for patients who were clear. So, about 20% of patients achieved an IGA of 0, and at that point, they switched from daily application to twice weekly application,” Melinda Gooderham, MSc, MD, FRCPC, medical director at SKiN Centre for Dermatology in Peterborough, Ontario, Canada, and late-breaker presenter, told Dermatology Times.

Other key results from INTEGUMENT-OLE include:

• 66.2% and 64.6% of patients who rolled over from the roflumilast cream arm in INTEGUMENT-1 or -2 or switched to once-daily roflumilast cream 0.15% from the vehicle arm demonstrated a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75) after 56 weeks, respectively
• 56.9% and 50.0% of patients who rolled over from or switched to once-daily roflumilast cream 0.15% treatment achieved a significant reduction (≥4-point) in itch based on daily Worst Itch Numeric Rating Scale (WI-NRS) (among patients aged ≥12 years with baseline WI-NRS ≥4) at week 56, respectively

According to the announcement, the long-term study results provide further support of the safety and tolerability of roflumilast cream that was already seen in INTEGUMENT-1 (NCT04773600) and INTEGUMENT-2 (NCT04773600). The overall incidence of adverse events was low, with the most frequently reported adverse events being COVID-19, upper respiratory tract infection, nasopharyngitis, and headache. Overall, only 3.0% of patients discontinued the trials due to adverse events.

“A lot of studies have looked at patient preferences for topical therapies. There was one study that looked at the number of flares per year, and what they found were patients were delaying treating a flare by about 7 days on average, because they were reluctant to use their topical corticosteroids,” said Gooderham.

She added, “Patients, I think, would prefer a non-steroidal option. But, unfortunately, many that we have available now come with issues of burning and stinging, so to have a new treatment option that has shown efficacy with twice weekly maintenance dosing without the burning and stinging is going to really change the way we treat our patients,” concluded Gooderham.

References

1. Arcutis announces new long-term data of roflumilast cream 0.15% for the treatment of mild to moderate atopic dermatitis (ad) in adults and children down to age six presented at Revolutionizing Alopecia Areata, Vitiligo, and Eczema Conference. News release. Arcutis Biotherapeutics. June 10, 2024. Accessed June 10, 2024. https://www.arcutis.com/arcutis-announces-new-long-term-data-of-roflumilast-cream-0-15-for-the-treatment-of-mild-to-moderate-atopic-dermatitis-ad-in-adults-and-children-down-to-age-six-presented-at-revolutionizing-alopecia/
2. FDA accepts Arcutis’ supplemental new drug application for roflumilast cream 0.15% for the treatment of atopic dermatitis in adults and children down to age 6. Arcutis Biotherapeutics. November 29, 2023. Accessed June 10, 2024. https://investors.arcutis.com/news-releases/news-release-details/fda-accepts-arcutis-supplemental-new-drug-application