Taku Fukuzawa and Junichi Nezu* Pages 1 - 8 ( 8 )
Background: Dysregulation of the complement system is linked to the pathogenesis of a variety of hematological disorders. Inhibition of complement component 5 (C5) with eculizumab has resulted in significant reduction of hemolysis, reduction of thromboembolic events and increased survival in patients with paroxysmal nocturnal hemoglobinuria (PNH). However, because of high levels of C5 in plasma, eculizumab requires frequent intravenous infusions and some patients may still experience breakthrough hemolysis. This review introduces the recent body of knowledge on recycling technology and discusses the likely therapeutic benefits of SKY59, a novel recycling antibody, for PNH and complement-mediated disorders.
Methods: By applying the recycling technology through pH-dependent binding to C5, we generated a novel humanized antibody against C5, SKY59.
Results: In cynomolgus monkeys, SKY59 suppressed C5 function and complement activity for significantly longer than a conventional antibody. Furthermore, SKY59 showed neutralizing effect on C5 variant p.Arg885His, while eculizumab does not inhibit complement activity in patients carrying this mutation.
Conclusion: SKY59 is a promising anti-C5 agent with significant advantages over current therapies such as long duration of action and efficacy against C5 variants.
Recycling technology, Antibody therapeutics, Complement system, C5, Paroxysmal nocturnal hemoglobinuria &emsp
Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka