A Comprehensive Monograph on Delgocitinib (DB16133): A First-in-Class Topical Pan-JAK Inhibitor

Executive Summary

Delgocitinib is a novel, small-molecule, topical pan-Janus kinase (JAK) inhibitor that represents a significant advancement in the treatment of inflammatory dermatological conditions. It functions by competitively inhibiting the adenosine triphosphate (ATP) binding site of all four members of the JAK family—JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2)—thereby disrupting the JAK-Signal Transducer and Activator of Transcription (STAT) signaling pathway.[1] This pathway is fundamental to the cellular response to a wide array of pro-inflammatory cytokines and is a critical driver in the pathophysiology of diseases such as eczema.

The primary clinical indication for delgocitinib in the United States and Europe is the topical treatment of moderate-to-severe chronic hand eczema (CHE) in adults for whom conventional therapies like topical corticosteroids are inadequate or inappropriate.[1] Its approval for this indication was based on robust evidence from the pivotal Phase 3 DELTA 1 and DELTA 2 clinical trials, which demonstrated statistically significant and clinically meaningful improvements in signs and symptoms of CHE, including itch and pain, compared to a vehicle cream.[7] In Japan, delgocitinib is approved for the treatment of atopic dermatitis (AD) in both adult and pediatric populations.[2]