JAMA Publishes Roflumilast Cream Phase 3 Trial Results for Plaque Psoriasis

The Journal of the American Medical Association (JAMA) published positive results from 2 pivotal phase 3 trials, DERMIS-1 and DERMIS-2, evaluating roflumilast cream 0.3% (ZORYVE; Arcutis Biotherapeutics) for plaque psoriasis.¹ The study data showed roflumilast cream achieved many significant improvements across multiple endpoints, including plaque and itch clearance at 8 weeks in adults and adolescents with plaque psoriasis.

The DERMIS-1 and DERMIS-2 trials were identical phase 3 randomized, parallel, double-blind, vehicle-controlled, multi-national, multi-center studies where roflumilast cream or matching vehicle cream were applied once a day for 8 weeks to participants aged 2 years and older with mild, moderate, or severe chronic plaque psoriasis involving between 2% and 20% body surface area. DERMIS-1 enrolled 439 participants and DERMIS-2 enrolled 442 participants.²

Results showed that in both studies, significantly more participants treated with roflumilast cream reached Investigator's Global Assessment (IGA) Success at week 8 compared to the control group of vehicle-treated participants (DERMIS-1: 42.4% vs 6.1%; DERMIS-2: 37.5% vs. 6.9%, P<0.001 for both). Participants with clinically significant itch, measured by a baseline Worst Itch Numerical Rating Scale (WI-NRS) of greater than or equal to 4, achieved a 4-point reduction in WI-NRS at week 8 (DERMIS-1: 67.5% vs 26.8%; DERMIS-2: 69.4% vs 35.6%, P<0.001). Itch improvement was achieved after 2 weeks, the earliest timepoint measured (DERMIS-2: P=0.003), with consistent improvements seen through week 8.

Roflumilast cream was successful in intertriginous areas, where two areas of skin may rub together, with significantly more roflumilast-treated participants achieving Intertriginous IGA (I-IGA) success at week 8 than vehicle-treated patients (DERMIS-1: 71.2% vs. 13.8%; DERMIS-2: 68.1% vs 18.5%, P<0.001 for both), with most of the participants achieving I-IGA=0 (clear).

"I confess that I was perhaps not paying enough attention to roflumilast during its development, but I am impressed by these results. What really stood out to me was seeing some 70% of patients get clear or almost clear in the intertriginous areas- a delicate location that is generally not suitable for longer-term corticosteroid use. This, along with seeing itch improvement at 2 weeks, the once daily application, and a favorable safety and tolerability profile have me very interested.," said Peter Lio, MD, clinical professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine in Chicago, Illinois.

Compared to the vehicle, roflumilast cream showed improvement in psoriasis at all timepoints, measured by the Psoriasis Area Severity Index (PASI). In both trials, approximately 40% of participants achieved a 75% reduction in PASI scores (PASI-75) by week 8 (DERMIS-1: 41.6% vs 7.6%; DERMIS-2: 39.0% vs 5.3%, P<0.001 for both). Roflumilast cream also significantly improved patient-reported signs and symptoms, measured by significantly greater improvements in the Psoriasis Symptom Diary.

Roflumilast cream and vehicle safety and tolerability were similar, including pooled rates of treatment-related treatment-emergent adverse events (AEs) (4.0% roflumilast vs. 3.6% vehicle), any AE leading to discontinuation (1.0% roflumilast vs 1.3% vehicle) and application site pain (1.0% roflumilast vs 0.3% vehicle). There were no reported serious AEs, and local tolerability was positive for roflumilast cream as reported by participant and investigator assessment of irritation, burning, and stinging.

"Good access to the medication will hopefully allow for clinical experience, and while we have many powerful systemic agents for psoriasis, I still firmly believe that topical therapy is an important part of its care," said Lio.

Roflumilast cream 0.3% was approved by the US Food and Drug Administration in July 2022. Approximately 9 million people in the US suffer from plaque psoriasis, including adolescents and adults.³ Topical therapies have typically been the primary treatment option for plaque psoriasis, but determining a treatment plan has not always been easy. Plaque psoriasis affects different parts of the body, including areas like the face, elbows, knees, genitalia, and other areas of skin-to-skin contact. With varying degrees of skin sensitivities in each area, some cases require multiple topical medication prescriptions which can become complicated and frustrating.

Disclosure:

Lio was not involved in the DERMIS-1 and DERMIS-2 trials and has not worked with Arcutis Biotherapeutics.

References:

1. Lebwohl MG, Kircik LH, Moore AY, et al. Effect of roflumilast cream vs vehicle cream on chronic plaque psoriasis: The DERMIS-1 and DERMIS-2 randomized clinical trials. JAMA. 2022;328(11):1073–1084. doi:10.1001/jama.2022.15632
2. Journal of the American Medical Association publishes roflumilast cream 0.3% results from pivotal dermis-1 and -2 phase 3 trials in plaque psoriasis. Arcutis Biotherapeutics. Published September 20, 2022. Accessed September 20, 2022. https://www.arcutis.com/journal-of-the-american-medical-association-publishes-roflumilast-cream-0-3-results-from-pivotal-dermis-1-and-2-phase-3-trials-in-plaque-psoriasis/
3. FDA approves arcutis’ zoryve (roflumilast) cream 0. 3% for the treatment of plaque psoriasis in individuals age 12 and older. Arcutis Biotherapeutics. Published July 29, 2022. Accessed September 20, 2022. https://www.arcutis.com/fda-approves-arcutis-zoryve-roflumilast-cream-0-3-for-the-treatment-of-plaque-psoriasis-in-individuals-age-12-and-older/