Study: Roflumilast Foam Data Announced for both Psoriasis and Seborrheic Dermatitis

Two poster presentations for roflumilast foam (ARQ-154, Arcutis Biotherapeutics Inc) were recently presented at the European Academy of Dermatology and Venereology (EADV) 30th annual conference, September 29 to October 2.^{1, 2} 

Roflumilast, a selective and highly potent phosphodiesterase-4 inhibitor that is currently available only as an oral treatment for COPD, is being investigated for once-daily, nonsteroidal treatment of several dermatologic conditions.

The first poster presented was a randomized, double-blind, vehicle-controlled 8-week phase 2a study (NCT04091646) that evaluated once daily roflumilast foam 0.3% for patients diagnosed with moderate to severe seborrheic dermatitis (SD).¹ According to the poster, current topical treatments for SD are antifungals, steroids, immunomodulators, and dandruff shampoos.

Eligible patients were those aged 18 years or older with a clinical diagnosis of SD of at least 3 months’ duration, an Investigator Global Assessment (IGA) score greater than or equal to 3 (moderate) and affecting less than or equal to 20% of the body surface area (BSA), including the scalp, face, trunk, and/or intertriginous areas.

The 226 patients were randomized in a 2:1 ratio of roflumilast foam 0.3% (154) or vehicle foam (72), which was applied once daily to lesions of SD. The groups had similar demographics. The intention-to-treat (ITT) population included all randomized patients, while the modified intent-to-treat (mITT) population included all randomized patients except for 2 patients who missed the Week 8 IGA assessment due to the COVID-19 disruption.¹ 

The primary efficacy analysis was based on the mITT population and repeated for the ITT population. The primary efficacy endpoint was analysed using a Cochran-Mantel-Haenszel test stratified by study site and baseline disease severity; statistical significance was concluded at the 10% significance level (2-sided).¹

Of the total number, 92% of patients completed the study. Roflumilast foam 0.3% demonstrated significant and rapid improvement in SD with 33.8%, 56.6%, and 73.8% of patients in the treatment arm achieving success (defined as a score of clear or almost clear and at least a 2 grade improvement from baseline) at weeks 2, 4, and 8, respectively. Additionally, roflumilast foam 0.3% significantly improved erythema success, scaling success, and itch. It also reduced the BSA affected and improved Dermatology Life Quality Index (DLQI).¹

It was found that the rates of adverse events (AEs) were low, and few were treatment related (TRAE). The rates of discontinuation due to AE were similar between the vehicle and roflumilast groups and there were no serious AEs. The most common TRAEs were contact dermatitis (1.9%), insomnia (1.9%), and nasopharyngitis (1.9%) for the roflumilast arm. Application site pain or burning were less than 1% in the roflumilast-treated group.

The other poster presented was a 8-week randomized, double-blind, vehicle-controlled phase 2b study (NCT04128007) on once-daily roflumilast foam 0.3% as a treatment option for patients with psoriasis with itch. Eligible patients were those aged 12 years or older with scalp and body psoriasis for at least 6 months.²

The 304 patients were randomised 2:1 into roflumilast foam 0.3% (200; 198 received treatment) or vehicle foam (104). Most patients (83.7% to 88.5%) completed the study.

The primary efficacy endpoint was scalp-IGA (S-IGA), which was defined as patients who achieved S-IGA 0/1 (clear or almost clear) and a 2-grade improvement from baseline at week 8. The efficacy endpoints were analysed by the Cochran-Mantel-Haenszel test, baseline S-IGA, and baseline body-IGA (B-IGA) category using multiple imputation for missing data.

Roflumilast foam significantly improved scalp (17.4%, 41.3%, 59.1%) and body psoriasis (9.5%, 21.3%, 40.3%) at weeks 2, 4, and 8, respectively, while also demonstrating significantly improved scalp (44.6%, 62.0%, 71.0%) and body itch (45.3%, 57.0%, 68.2%) by week 2 through week 8. Also, the roflumilast foam significantly improved patient-reported severity and burden of itch as indicated by improvements on the Psoriasis Symptom Diary (PSD) Items 1 (Severity of Itch, -59.6% by week 8) and 2 (Burden of Itch, -60.6% by week 8). It also provided an increase in quality of life as indicated by the Dermatology Life Quality Index.

There were 23.2% of patients with treatment emergent adverse events (TEAEs). The most common TEAEs were application site pain, COVID-19, psoriasis, sinusitis, hypertension, and diarrhea.²

Both studies found roflumilast to be well tolerated and efficacious, which may warrant further investigation.¹²

Disclosures:

MZ, JD, LK, AM, LSG, JA-L, MB, SB, KE, LJG, STG, LKF, SF, SEK, EL, CWL, DMP, DPT, and PSY are investigators and/or consultants for Arcutis Biotherapeutics, Inc. and received grants/research funding and/or honoraria; AF, RCH, PB, and DRB are employees of Arcutis Biotherapeutics, Inc. Additional disclosures provided on request.

AYM, JA-L, NB, MB, ARD, ZDD, MJG, SEK, LHK, KAP, DMP, MS, RS, and MZ are investigators and/or consultants for Arcutis Biotherapeutics, Inc. and received grants/research funding and/ or honoraria; AF, PB, RCH, and DRB are employees of Arcutis Biotherapeutics, Inc. Additional disclosures provided on request.

References:

1. Zirwas M, Draelos Z, DuBois J, et al. A Randomized, Double-blind, Vehicle-Controlled Phase 2a Study Evaluating Once Daily Roflumilast Foam 0.3% in Patients With Moderate to Severe Seborrheic Dermatitis. Presented at: EADV 30th Annual Congress 2021. 

2. Moore A, Alonso-Llamazares J, Bhatia N, et al. Once-Daily Roflumilast Foam 0.3% Improves Severity and Burden of Itch in Patients With Scalp and Body Psoriasis in a Randomized, Double-blind, Vehicle-Controlled Phase 2b Study. Presented at: EADV 30th Annual Congress 2021.