Chronic inflammatory skin diseases are estimated to affect 20–25% of the world’s population and the medical need persists for new safe and effective oral drugs for long-term treatment of chronic inflammatory skin diseases.

A new class of selective phosphodiesterase 4 subtype B and subtype D (PDE4B/D) inhibitors is emerging as four selective PDE4B/D inhibitor drug candidates (nerandomilast, zatolmilast, orismilast, and PF-07038124) are currently in late-stage clinical trials for diseases of the lung, brain, and skin.

Short isoforms of PDE4B/D—in particular PDE4B2 and PDE4D1/D2—are critical isoforms to block to achieve anti-inflammatory effects, and selective PDE4B/D inhibitors may drive higher efficacy than previously approved pan-phosphodiesterase 4 (pan-PDE4) inhibitors.

Next generation PDE4B/D inhibitors also have potential to affect comorbidities that are associated with chronic inflammatory skin diseases, including cardiometabolic disease.