Arcutis Biotherapeutics recently announced the submission of a New Drug Application (NDA) for its topical phosophodiesterase 4 (PDE4) inhibitor, roflumilast cream (ARQ-151), in the treatment of mild-to-severe plaque psoriasis (PsO). Despite having a potential commercial advantage as the first topical PDE4 inhibitor for an underserved PsO patient segment, GlobalData, a leading data and analytics company, notes that Arcutis may still face several challenges when marketing roflumilast cream.

Tiffany Chan, Immunology Analyst at GlobalData, comments: “Over the last decade, the PsO pipeline has been dominated by injectable biologics targeting moderate and severe disease, while topical therapies have strikingly lacked innovation. Recently this has begun to change with the launch of novel formulations of calcipotriene/betamethasone combination therapies, such as LEO Pharma’s Enstilar foam in 2015 and EPI Health/MC2 Therapeutics’ Wynzora Cream launching this past July. The late-stage PsO pipeline holds further innovation for topical therapies. If approved by the FDA, Arcutis’ roflumilast would become the second PDE4 inhibitor to enter the PsO market (after Amgen’s oral agent, Otezla) and the first topical PDE4 inhibitor for the disease.”

The company’s NDA submission is based on two pivotal Phase III studies, DERMIS-1 (NCT04211363) and DERMIS-2 (NCT04211389). Roflumilast, as a molecule, is already approved in oral tablet form (500mg) for chronic obstructive pulmonary disease, under the brand name Daliresp, which is currently marketed by AstraZeneca. The topical cream formulation by Arcutis is in development for PsO as well as atopic dermatitis.

Ms. Chan continues: “One challenge Arcutis could face is that it’s not only a newcomer to the mature PsO market, but to the pharma market as a whole—topical roflumilast cream would represent the company’s first marketed asset for any indication. Still, the company’s reputation (or lack thereof) is not expected to impede regulatory decisions. If the company were to partner with a more established player in the PsO space such as AbbVie, Pfizer, or Janssen, it could expand its reach and obtain a stronger foothold in the market.

“Additionally, roflumilast cream is expected to be the one of two innovative branded topical therapies approved for PsO in the near future. Key opinion leaders interviewed by GlobalData anticipate that roflumilast cream will be directly competing with Dermavant’s topical arylhydrocarbon receptor (Ahr) agonist, tapinarof cream, which is under regulatory review by the FDA as of August 2021.”

Roflumilast, and other late-stage PsO pipeline agents (both topical and oral), signal a changing of the guard in terms of market development. Primary research conducted by GlobalData indicates that given the options of oral, subcutaneous, and topical therapies, PsO patients generally prefer topical therapies (followed by oral) and it appears that drug manufacturers are finally moving away from the biologic focus of the last decade to meet this remaining need. Historically, much of the clinical and research focus has been on treating the most severe patients but roflumilast cream and other newer drugs will finally address milder populations, which have been somewhat neglected until now.