Natalizumab: alpha 4-integrin antagonist selective adhesion molecule inhibitors for MS.
Natalizumab (Antegren, Elan Corp. plc.; Biogen Idec.) is the first alpha4-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 alpha4-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 (approximately 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-beta-1a are underway in patients with relapsing-remitting multiple sclerosis. Natalizumab may be an important addition to the therapeutic armamentarium for multiple sclerosis.
Rudick
Richard A
RA
Department of Neurology, Center for Multiple Sclerosis Treatment and Research, Cleveland, OH 44195, USA. rudickr@ccf.org
Sandrock
Alfred
A
D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D039441:Integrin alpha4 / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D000069442:Natalizumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015815:Cell Adhesion Molecules; D000069442:Natalizumab; D039441:Integrin alpha4