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Erlizumab, also known as rhuMAb, is a recombinant humanized monoclonal antibody that was an experimental immunosuppressive drug. Erlizumab was developed by Genentech under a partnership with Roche to treat heart attack, stroke, and traumatic shock.
Mechanism of action
The drug works by blocking a growth factor in blood vessels. Specifically, erlizumab targets CD18 and an LFA-1 integrin. Erlizumab was meant to stop lymphocyte movement into inflamed tissue, thereby reducing tissue damage.
Genentech started clinical trials on the drug in October 1996. During clinical trials, six patients suddenly started coughing up blood, and four of them later died. In June 2000, preliminary phase II clinical trial results showed that erlizumab did not meet Genentech's goals. Genentech's primary goal was for the drug to increase blood flow to the heart within 90 minutes of administering the medicine.
Other anti-CD18 drugs
Multiple companies have tried to develop anti-CD18 drugs, but none of them have been successful. Among them are Icos's rovelizumab (LeukArrest), and two drugs developed by Protein Design Labs (PDL) and Centocor. Although trials in humans have not gone well, the research of CD18 drugs in animals has been encouraging. It is thought that the experimental medicines are affecting the lymphocyte adhesion pathway in humans in unintended ways. One hypothesis is that the endothelial cell barrier function fails when blood supply is low for a prolonged time in humans. If this is true, the drug is not able to stop lymphocyte movement into inflamed tissue.
- "Genentech Announces Phase II Trial of Experimental Anti-CD18 Antibody Did Not Meet Its Primary Objectives". Business Wire. June 16, 2000. Retrieved January 29, 2009.
- Altman, Lawrence (May 30, 2000). "THE DOCTOR'S WORLD; In Search of Surprises as Cures for Cancer". The New York Times. Retrieved January 29, 2009.
- Hehlgans, Stephanie; Michael Haasea and Nils Cordes (January 2007). "Signalling via integrins: Implications for cell survival and anticancer strategies". Biochimica et Biophysica Acta (BBA) 1775 (1): 163–80. doi:10.1016/j.bbcan.2006.09.001. PMID 17084981.
- Dove, Alan (2000). "CD18 trials disappoint again". Nature Biotechnology 18 (8): 817–8. doi:10.1038/78412. PMID 10932141.
- "Genentech Reports 1996 Third Quarter Results". Genentech. October 21, 1996. Retrieved January 31, 2009.
- Barran, Kenneth; Michel Nguyen; George R. McKendall; Costas T. Lambrew; Gary Dykstra; Sebastian T. Palmeri; Raymond J. Gibbons; Steven Borzak; Burton E. Sobel; Steven G. Gourlay; Amy Chen Rundle; C. Michael Gibson; Hal V. Barron (December 4, 2001). "Double-Blind, Randomized Trial of an Anti-CD18 Antibody in Conjunction With Recombinant Tissue Plasminogen Activator for Acute Myocardial Infarction". Circulation 104 (23): 2778–83. doi:10.1161/hc4801.100236. PMID 11733394.