An Analytical Monograph on Peficitinib (DB11708): A Pan-Janus Kinase Inhibitor for Rheumatoid Arthritis

Executive Summary

Peficitinib, marketed under the brand name Smyraf®, is an orally administered, once-daily small molecule drug classified as a targeted synthetic disease-modifying antirheumatic drug (tsDMARD). It functions as a pan-Janus kinase (pan-JAK) inhibitor, a class of immunomodulatory agents that target the intracellular JAK-STAT signaling pathway. Developed by Astellas Pharma, Peficitinib has received regulatory approval in Japan, South Korea, and Taiwan for the treatment of rheumatoid arthritis (RA), including the prevention of structural joint damage, in adult patients who have demonstrated an inadequate response to conventional therapies.

The primary mechanism of action of Peficitinib involves the competitive and reversible inhibition of all four members of the Janus kinase family: JAK1, JAK2, JAK3, and Tyrosine Kinase 2 (TYK2). By blocking the activity of these enzymes, Peficitinib interrupts the signal transduction of a wide array of pro-inflammatory cytokines that are pivotal in the pathogenesis of RA. This leads to the suppression of immune cell activation, a reduction in systemic inflammation, and the mitigation of joint destruction. While classified as a pan-inhibitor, in vitro data reveal a nuanced selectivity profile, with the most potent activity against JAK3, which may contribute to its specific therapeutic window.