Clinical Development

Topical roflumilast cream (ARQ-151) is a small molecule inhibitor of phosphodiesterase type 4 (PDE4), an intracellular enzyme that increases the production of proinflammatory mediators and decreases production of anti-inflammatory mediators, and has been implicated in a wide range of inflammatory diseases including psoriasis, eczema, and chronic obstructive pulmonary disease (COPD). PDE4 is an established target in dermatology, and other PDE4 inhibitors have been approved by the FDA for the topical or systemic treatment of plaque psoriasis and atopic dermatitis. Topical roflumilast cream is a highly potent, selective PDE4 inhibitor in a convenient, once-daily formulation that Arcutis is developing for chronic plaque psoriasis and atopic dermatitis. Roflumilast is 25–300X more potent than the two other FDA-approved PDE4 inhibitors used in dermatology and has a well-established safety profile with more than 1 million patient years of exposure in clinical use.

In our plaque psoriasis development program, we have completed a 332-patient Phase 2b study and an 89-patient Phase 2a study of topical roflumilast cream. In the recent Phase 2b study, topical roflumilast cream produced statistically significant reductions compared to vehicle in the signs of plaque psoriasis, and also demonstrated excellent safety and tolerability in this population. We also recently completed two pivotal Phase 3 studies of topical roflumilast cream in plaque psoriasis, and expect to release data from those trials in Q1 2021.  Topical roflumilast potentially delivers efficacy comparable to a high potency steroid, but with safety and tolerability that enables chronic use in all areas of the body, and little or none of the local tolerability issues associated with competitive agents. Based on the clinical data we have generated to date, we believe that topical roflumilast cream is uniquely suited to address the unmet needs in topical treatment of psoriasis, offering efficacy comparable to a high potency steroid, but with safety and tolerability that enables chronic use in all areas of the body, and little or none of the local tolerability issues associated with competitive agents. Topical roflumilast has the potential to solve many of the problems with existing therapies that bedevil physicians and patients, enabling physicians to maximize patient outcomes in inflammatory dermatological conditions.

In our atopic dermatitis development program, we have completed a 136-patient Phase 2 proof-of-concept study of topical roflumilast cream.  In this study, topical roflumilast cream demonstrated consistent evidence of symptomatic improvement across endpoints and favorable tolerability in this patient population.  The higher dose tested demonstrated trend towards significance on primary endpoint.  Both doses tested were statistically superior to vehicle on key secondary endpoints. We are advancing topical roflumilast cream development into Phase 3 in atopic dermatitis in Q4 2020 or Q1 2021.