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Synonyms: AN100226 | anti-alpha4 integrin | anti-VLA4 | Tysabri®
natalizumab is an approved drug (FDA (2004), EMA (2006))
Compound class:
Antibody
Comment: 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]. Biosimilars: The first natalizumab biosimilar was approved by the FDA in August 2023 and by the EMA a month later. 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 |
| No information available. |
Summary of Clinical Use  |
| Used in the treatment of relapsing forms of multiple sclerosis, and in the management of Crohn's disease. However, natalizumab is not widely prescribed due to safety concerns around induction of progressive multifocal leukoencephalopathy (PML). |
| Mechanism Of Action and Pharmacodynamic Effects |
| Binds to the α4-subunit of α4β1 and α4β7 integrins on leukocyte cell surfaces [2] which inhibits the adhesion of leukocytes to their counter-receptor, vascular cell adhesion molecule-1 (VCAM-1). This action limits T cell migration to inflamed tissue, thereby reducing active inflammation. |
| Clinical Trials | |||||
| Clinical Trial ID | Title | Type | Source | Comment | References |
| NCT02176031 | Phase II Trial of Natalizumab + Prednisone for Initial Therapy of Acute GI GVHD | Phase 2 Interventional | Dana-Farber Cancer Institute | Trial results indcated that initial treatment of acute gastrointestinal GvHD with natalizumab plus corticosteroids is safe, effective, and produces a durable response. | 1 |
| External links |
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For extended ADME data see the following: Electronic Medicines Compendium (eMC) Drugs.com European Medicines Agency (EMA) |
