Rovelizumab (ICOS Corp).
Rovelizumab is a humanized monoclonal leukointegrin antibody under development by ICOS as a potential treatment for multiple sclerosis (MS), hemorrhagic shock, myocardial infarction (MI) and stroke. ICOS announced the commencement of phase II studies in MS patients experiencing acute exacerbations in January 1997; a randomized, double-blind, placebo-controlled phase III trial for acute ischemic stroke, to involve 800 patients, was initiated in January 1999 [312467,313014]. The compound is also undergoing preclinical investigation for cerebral vasospasm, head trauma, kidney transplantation and restenosis [346437]. In September 1999, results from a phase II clinical trial in 45 patients suffering from acute exacerbations of MS were presented at the Warburg Dillion Read Global Life Sciences Conference (New York). The study was designed to evaluate the safety and efficacy of four weekly doses of rovelizumab, as compared to placebo. Rovelizumab was shown to be safe, but demonstrated no clinical benefit for the recovery of neurological functioning [341638]. In February 1997, ICOS announced the initiation of a phase II trial in MI. The placebo-controlled trial is being coordinated by the Mayo Physician Alliance for Cardiovascular Trials and will evaluate safety, pharmacokinetics and infarct size in 60 patients [234046,264363]. Patient enrollment for this, and an open label phase II trial in trauma-induced hemorrhagic shock, was completed in September 1997 [264363]. An expanded shock trial in 150 trauma patients, is expected to complete enrollment by the end of 1998 [296831]. An expanded trial for MI was also planned [264363]. The company is to evaluate rovelizumab in patients with ischemic stroke, and a double-blind, dose-escalating, placebo-controlled phase II trial has been initiated at several centers in the US [264363]. A patient population of 48 was tested, with patient dosing occurring within 12 h of stroke onset symptoms. There was no significant difference in SAEs between rovelizumab and placebo treatment, and no immunogenicity was observed [315799]. Neuroprotection was observed in a rabbit model of focal ischemia, with greatest reduction in infarct noted in the cortical areas of the brain. Neutrophil infiltration to ischemic brain parenchyma was reduced by 90% [315799]. Rovelizumab is a monoclonal antibody directed against the CD11/CD18 cell adhesion proteins. By binding to these receptors, rovelizumab prevents the migration and adhesion of neutrophils in the central nervous system, which may cause brain inflammation and neuronal loss [167725]. Rovelizumab binds to all four known leukointegrin receptors, blocking neutrophil adhesion and binding to ICAMs [307344]. ICOS collaborated with the University of Washington on the preclinical development of this compound [175193].
Jones
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Trinity Cottage, Killiney Hill Road, Killiney, Co Dublin, Ireland, rjj101@excite.com