Reduced WBC and lymphocytes; lymphoid depletion in spleen, thymus, lymph nodes and GALT
“The target organs were identified as lymphoid organs in both species, with major study findings including reduced circulating white blood cells and lymphocytes and decreased lymphocytes/cellularity in various lymphoid tissues (including spleen, thymus, lymph nodes, and gut-associated lymphoid tissue).”
✓ VerifiedFDA multi-discipline review, p. 50Source ↗
Biodistribution & persistence
Excreted in rat milk; milk/plasma ratios ~7 to 20 over 8 hours
“Milk/plasma concentration ratios were approximately 7, 13, 19, and 20 at 1 hr, 2 hr, 4 hr, and 8 hr postdose, respectively.”
✓ VerifiedFDA multi-discipline review, p. 48Source ↗
Modality-specific risk
Exaggerated JAK pharmacology: lymphoid organ toxicity with reduced white cells and lymphocytes
“The major safety signals identified in these studies were consistent with deuruxolitinib’s pharmacological activity. The target organs were identified as lymphoid organs in both species, with major study findings including reduced circulating white blood cells and lymphocytes”
✓ VerifiedFDA multi-discipline review, p. 45Source ↗