Natalizumab was the first migration-inhibitory biological drug to be approved for inflammatory diseases. It targets α4β1 integrin (VLA-4) on leukocytes to block interaction with vascular cell adhesion molecule 1 (VCAM-1) on inflamed endothelium, thus inhibiting leukocyte extravasation into sites of inflammation. It is active in peripheral tissues and the central vervous system.
Targeting cell migration-related molecules in immune conditions (and cancer) is regarded as a valid approach for the development of novel anti-inflammatory therapeutics [3
]. The design and synthesis of this antibody was originally described in a 1997 publication [2
The first natalizumab biosimilar was approved by the FDA in August 2023. Like the originator/reference agent, Tyruko® (natalizumab-sztn; Sandoz Inc.) is indicated for relapsing forms of multiple sclerosis and moderate-severe active Crohn's disease (when conventional therapies, including TNF-α inhibitors, are inadequate or not tolerated).
View more information in the IUPHAR Pharmacology Education Project: natalizumab