Roflumilast Cream Improves Signs and Symptoms of Plaque Psoriasis: Results from a Phase 1/2a Randomized, Controlled Study

August 2020 | Volume 19 | Issue 8 | Original Article | 734 | Copyright © August 2020


Published online July 15, 2020

Kim A Papp MD PhDa, Melinda Gooderham MS MDb, Michael Droege PhDc, Charlotte Merritt MBAc, David W. Osborne PhDc, David R. Berk c, Archie W. Thurston Jr. PhDd, Valerie H. Smith MState, Howard Welgus MDc

aProbity Medical Research and K. Papp Clinical Research, Ontario, ON, Canada bSKiN Centre for Dermatology and Probity Medical Research, Peterborough Queens University Kingston, ON, Canada cArcutis Biotherapeutics, Inc., Westlake Village, CA dADME Solutions, Inc., San Diego, CA ePremier Research, Research Triangle Park, NC

Abstract
Background: Roflumilast cream (ARQ-151) is a highly potent, selective phosphodiesterase-4 inhibitor in development for once-daily topical treatment of chronic plaque psoriasis.
Objectives: To assess the safety and efficacy of once-daily roflumilast cream 0.5% and 0.15% in patients with chronic plaque psoriasis.
Methods: This phase 1/2a study enrolled a single-dose, open-label cohort (Cohort 1: 0.5% cream applied to 25 cm² psoriatic plaques), and a 28-day, double-blinded cohort (Cohort 2: 1:1:1 randomization to roflumilast cream 0.5%, 0.15%, or vehicle). Patients had chronic plaque psoriasis of >6 months’ duration with ≤5% body surface area involvement. Outcomes included safety (adverse events) and efficacy (percentage change in the Target Plaque Severity Score [TPSS] × Target Plaque Area [TPA]) at week 4.
Results: For Cohorts 1 (n=8) and 2 (n=89), adverse events (all mild/moderate; none severe or serious) were similar between active arms and vehicle. Treatment-related events were confined to the application site, without differences between drug and vehicle. No patient discontinued treatment due to adverse events. The primary efficacy endpoint was met for both roflumilast cream doses: TPSS×TPA improvement at week 4 was statistically significant for roflumilast 0.5% (P=0.0007) and 0.15% (P=0.0011) versus vehicle; significance was reached as early as 2 weeks. For both roflumilast cream doses, 66%–67% improvement from baseline was observed at week 4, without reaching a plateau, versus 38% improvement for vehicle.
Conclusion: Roflumilast cream was safe and highly effective at doses of 0.5% and 0.15% and represents a potential novel once-daily topical therapy for the treatment of chronic plaque psoriasis.
ClinicalTrials.gov #NCT03392168.

J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5370

INTRODUCTION

The primary goals of psoriasis treatment are to improve skin lesions and improve quality of life.1 The choice of treatment for chronic plaque psoriasis depends on the severity of disease. Although the new biologic therapies have heralded remarkable efficacy in patients with moderate to severe disease, patients with mild to moderate disease manage their psoriasis with topical therapies. Topical treatment is also often used adjunctively in patients on systemic therapy or phototherapy for resistant plaques.1,2 Topical treatments include corticosteroids, vitamin D analogues (calcipotriene), tar-based preparations, dithranol, salicylic acid, topical retinoids (tazarotene), and topical calcineurin inhibitors (tacrolimus and pimecrolimus), with corticosteroids and vitamin D analogues being the most commonly prescribed.1-3 Topical corticosteroids are effective for the treatment of psoriasis but are associated with adverse events (AEs): treatment may cause local reactions (eg, skin atrophy, striae, telangiectasia, and acne) and may be associated with systemic effects, rebound after discontinuation of treatment, and/or tachyphylaxis.1,3 Vitamin D analogues are not as effective as high-potency topical corticosteroids for psoriasis treatment and are more likely to cause local adverse reactions (eg, irritation).3 Treatment dissatisfaction is high among patients with psoriasis, underscoring the need for new treatment options.4

Roflumilast is a highly potent, selective phosphodiesterase-4 (PDE-4) inhibitor; an oral formulation is approved to treat acute exacerbations of chronic obstructive pulmonary disease.5 Rodoi: