Natalizumab: α4-integrin antagonist selective adhesion molecule inhibitors for MS

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Abstract

Natalizumab (AntegrenTM, Elan Corp. plc.; Biogen Idec.) is the first α4-integrin antagonist in the class of selective adhesion molecule inhibitors and is in Phase III clinical trials for the treatment of multiple sclerosis. After a 300 mg intravenous infusion, natalizumab has an elimination half-life of 6 to 9 days, but α4-integrin receptors expressed on the surface of peripheral blood leukocytes are more than 80% saturated approximately 1 month postinfusion. Therefore, natalizumab is given as a 300 mg dose administered monthly. Preliminary efficacy results showed a marked reduction (˜90%) in the formation of new gadolinium-enhancing lesions and reduced the number of patients with relapse by 50% in patients with relapsing-remitting or secondary progressive multiple sclerosis receiving natalizumab versus those receiving placebo over a 6-month period. In clinical studies, natalizumab has demonstrated a favorable safety profile. Pivotal Phase III studies of natalizumab as monotherapy and in combination with intramuscular interferon-β-1a are underway in patients with relapsing-remitting multiple sclerosis. Natalizumab may be an important addition to the therapeutic armamentarium for multiple sclerosis.

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