FDA Approves Roflumilast Cream 0.15% For Atopic Dermatitis in Patients Aged 6 Years and Older

Image credit: © Calin - stock.adobe.com

Arcutis Biotherapeutics recently announced that the US Food and Drug Administration (FDA) has approved its supplemental new drug application (sNDA) for roflumilast (Zoryve) cream 0.15% for the treatment of patients aged 6 years and older with mild to moderate atopic dermatitis. Roflumilast cream is a once-daily, steroid-free topical designed to significantly reduce itch and manage atopic dermatitis long-term.¹

“What is really unique about the profile of Zoryve cream is that it works quickly, but it’s also appropriate for long-term treatment. Oftentimes, we would have to go to 2 different therapies in order to address these different parts of the treatment. For an atopic dermatitis patient, it’s important that you work quickly because this is a disease that has a lot of itching and symptoms that need to be relieved,” said Patrick Burnett, MD, PhD, FAAD, chief medical officer of Arcutis, in an interview with Dermatology Times.

See more below on expert insights from Burnett.

The FDA’s approval of Arcutis’ sNDA is based on positive results from the three phase 3 INTEGUMENT clinical trials, a phase 2 dose-ranging study, and two phase 1 pharmacokinetic studies. INTEGUMENT-1 (NCT04773587) and INTEGUMENT-2 (NCT04773600) were 2 identical, parallel-group, double-blind, vehicle-controlled, phase 3 clinical trials evaluating the safety and efficacy of roflumilast cream 0.15% or vehicle applied once-daily to affected skin for 4 weeks in 1337 adult and pediatric patients aged 6 years and older with mild to moderate atopic dermatitis.

In INTEGUMENT-1 and INTEGUMENT-2, each study met its primary end point of a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of clear (0) or almost clear (1) and a 2-grade improvement from baseline at week 4 (INTEGUMENT-1: 32.0% roflumilast cream vs. 15.2% vehicle, P<0.0001; INTEGUMENT-2: 28.9% roflumilast cream vs. 12.0% vehicle, P<0.0001). In both studies, 40% of adult and pediatric patients treated with roflumilast cream achieved a vIGA-AD score of 0 or 1 at week 4 (INTEGUMENT-1: 41.5% vs. 25.2%, P<0.0001; INTEGUMENT-2: 39% vs. 16.9%, P<0.0001), with significant improvement seen as early as week 1 (P<0.0001).

Over 40% of adult and pediatric patients treated with roflumilast cream achieved a 75% improvement in Eczema Area and Severity Index (EASI 75) at week 4 compared to vehicle (INTEGUMENT-1: 43.2% vs. 22.0%, P<0.0001; INTEGUMENT-2: 42.0% vs. 19.7%, P<0.0001). Patients treated with roflumilast also achieved significant improvements in EASI 75 compared to vehicle as early as week one in both INTEGUMENT studies.

Pediatric patients are an important factor in Arcutis’ roflumilast cream 0.15% approval, as it provides a non-steroidal topical for pediatric patients down to 6 years of age and their caregivers. In a recent roflumilast cream 0.15% media briefing, Lawrence Eichenfield, MD, professor of dermatology and pediatrics and vice-chair of the department of dermatology at UC San Diego School of Medicine, and an INTEGUMENT study investigator, addressed “steroid phobia” and misinformation on social media.

“The way patients and families hear information is different than before because they're searching out information directly, and therefore social media and unfiltered sources can influence their sense of the positives and negatives of medications. This is certainly a case of steroid phobia where there’s a heightened sense of steroid phobia that I truly think is beyond what really the risks are... It definitely sets up a situation where having effective non-steroidals that are safe and tolerant can certainly make families happier,” Eichenfield told Dermatology Times.

Expert Perspective With Patrick Burnett, MD, PhD

In an interview with Dermatology Times, Burnett discussed his unique perspective of being both a board-certified dermatologist and chief medical officer during the development of roflumilast cream 0.15% and what he views as the value of the non-steroidal topical cream. Burnett also discusses the important indication of pediatric patients in this approval of roflumilast cream and how roflumilast cream stands up in a world of atopic dermatitis treatments that also include injections, other topicals, and oral medications.

Safety and Long-Term Data

Regarding safety, roflumilast cream 0.15% was well-tolerated and treatment emergent adverse events (TEAEs) were low in both the roflumilast cream and vehicle treatment groups. No adverse reactions in both INTEGUMENT-1 and INTEGUMENT-2 occurred in more than 2.9% of patients in either group. The most common adverse events were headache (2.9%), nausea (1.9%), application site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%).

No new safety signals were seen during treatment up to 56 weeks in the INTEGUMENT-OLE open-label study (n=658). 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, 61.5% and 66.2% of patients who rolled over from the roflumilast cream arm in INTEGUMENT-1 or INTEGUMENT -2 demonstrated EASI 75 after 28 weeks and 56 weeks, respectively.^1,2

“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,” said Melinda Gooderham, MSc, MD, FRCPC, medical director at SKiN Centre for Dermatology in Peterborough, Ontario, Canada, and roflumilast cream 0.15% investigator, told Dermatology Times in a previous interview.

References

1. FDA approves Arcutis’ ZORYVE (roflumilast) cream 0.15% for the treatment of atopic dermatitis in adults and children down to 6 years of age. News release. Arcutis Biotherapeutics. July 9, 2024. Accessed July 9, 2024. https://investors.arcutis.com/news-releases/news-release-details/fda-approves-arcutis-zoryver-roflumilast-cream-015-treatment
2. 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 July 7, 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/