FDA Approves Roflumilast Cream for Adolescent, Adult Plaque Psoriasis


The indication to Arcutis makes the once-daily topical cream the first marketed PDE4 inhibitor of its kind.

FDA Approves Roflumilast Cream for Adolescent, Adult Plaque Psoriasis

The US Food and Drug Administration (FDA) has approved roflumilast cream (ZORYVE) 0.3% for the treatment of plaque psoriasis in patients aged ≥12 years old.

The indication granted to Arcutis Biotherapeutics makes the topical phosphodiesterase-4 (PDE4) inhibitor the first of its kind approved for treating plaque psoriasis. It also introduces a new, non-steroidal, daily agent to the armament of psoriasis treatment options, with supporting long-term data showing benefit in key symptoms including itch and patient tolerability.

Roflumilast cream’s approval was based on the findings from the phase 3 DERMIS trial. In data presented at the American Academy of Dermatology (AAD) 2022 Annual Meeting in Boston, investigators reported that patients significantly improved in proportion of treated patients achieving Investigator Global Assessment (IGA) scores for clear or almost clear skin at week 8 versus placebo (P <.0001).

The DERMIS investigative team also reported significant improvements in intertriginous IGA (I-IGA; P <.01), Psoriasis Area Severity Index 75% improvement (PASI-75; P <.0001) and Worst Itching Intensity Numerical Rating Scale (WI-NRS) improvement (P <.0001) among patients receiving roflumilast cream versus placebo through 8 weeks.

Last month, interim data from the 24-week open-label extension for DERMIS showed half of treated patients with psoriasis achieved IGA clear or almost clear skin at 24 weeks, while another three-fourths of patients achieved I-IGA improvement in the same time period. Investigators additionally observed favorable tolerability and no unexpected adverse events among the long-term treatment arm that achieved and maintained clear or almost clear skin.

In an interview with HCPLive, DERMIS author Mark Lebwohl, MD, professor and chair of the department of dermatology at Icahn School of Medicine at Mount Sinai, highlighted the “many advantages” once-daily roflumilast cream offers over the variety of previously available psoriasis treatments.

“For decades, the treatments we’ve been using are primarily topical corticosteroids,” Lebwohl said. “There are many of them on the market, they come in many shapes in forms, they’re very effective—but they’re associated with a number of adverse side effects.” Common topical steroid effects including irreversible stretch marks or temporary atrophy or facial rashes are not an issue with the PDE4 inhibitor cream.

Lebewohl also highlighted the uniquely beneficial properties of roflumilast cream for patients with differing effects of plaque psoriasis.

“Really, a dramatically effective treatment for facial and intertriginous skin—exactly the places where we get in trouble,” he explained. “But also, highly effective on non-facial or iintertriginous skin.”

Raj Chovatiya, MD, PhD, director of the Center for Eczema and Itch at Northwestern University Feinberg School of Medicine, told HCPLive that patients with mild-to-moderate plaque psoriasis have generally been without newer targeted therapies in the last 15 years—an anomaly given the rate of biologic therapy development and regulation in today’s dermatology.

“And that group of individuals are the ones that are heavily using topical therapy,” he said. “Typically, they have relatively low body surface area, that’s kind of the first place they want to start treating, it’s practical, it makes sense and there’s a lot of inflammation in the skin. So really, in some ways, it’s funny that our topical armamentarium hasn’t necessarily kept pace with where we’ve been at as far as systemic therapies.”

Roflumilast joins tapinarof cream as the latest non-steroidal topical option for psoriasis, Chovatiya said—though its function as a PDE4 inhibitor separates it from anything else available in the field.

“The reason why this is pretty exciting is because we know that phosphodiesterase-4 activity is highly elevated in psoriatic skin compared to healthy skin,” Chovatiya said. “And when you inhibit phosphodiesterase-4 activity, you get down-regulation of all those inflammatory cytokines and signals we think about with psoriasis.”

These inflammatory pathways, a byproduct of clinical breakthroughs and extensive research in the last decade, have informed dermatologists on the key avenues to mitigating the impact of chronic disease like psoriasis.

“And the cool thing about roflumilast is the degree to which it has such high affinity, binding and potency to PDE4,” Chovatiya said. “The estimate is anywhere from about 25- to almost 300-fold more potent than currently available PDE4 inhibitors.”

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