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Drugs of the Future
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Drugs Fut 2018, 43(7): 489
ISSN 0377-8282
e-ISSN 2013-0368
Copyright 2018 Clarivate
CCC: 0377-8282
DOI: 10.1358/dof.2018.043.07.2835326
 
 
Crizanlizumab. Anti-P-selectin monoclonal antibody, Prevention of sickle-cell-related pain crises
Kanter, J.
 
 
Vaso-occlusive crises (VOCs; also known as sickle-cell-related pain crises [SCPCs]), which are the hallmark of sickle cell disease (SCD), can be precipitated by microvascular occlusion, increased inflammation and physical/emotional distress. Despite the substantial burden of morbidity and mortality caused by VOCs, there is a paucity of approved preventive therapies that target the processes caused by SCD. Current options impose potential risk to the patient and have highly inconsistent therapeutic effects. Crizanlizumab is a first-in-class, recombinant, humanized monoclonal antibody that blocks interactions between P-selectin (a key VOC pathway modulator), and its ligand P-selectin glycoprotein ligand-1. Preclinical research has guided the initial clinical development of crizanlizumab, yielding insights into its pharmacokinetic/pharmacodynamic profile and immunogenic properties in healthy volunteers. A phase II study demonstrated that crizanlizumab 5.0 mg/kg significantly lowers the rate of SCPCs versus placebo, and identified no unexpected safety findings. Current findings provide hope that crizanlizumab can deliver disease-modifying effects that prevent VOCs.


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