Bigal Marcelo E, Walter Sarah, Rapoport Alan M
Vice President, Migraine & Headache Clinical Development, Teva Pharmaceuticals, Frazer, PA.
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY.
Br J Clin Pharmacol. 2015 Jun;79(6):886-95. doi: 10.1111/bcp.12591.
CGRP is an extensively studied neuropeptide that has been implicated in the pathophysiology of migraine. While a number of small molecule antagonists against the CGRP receptor have demonstrated that targeting this pathway is a valid and effective way of treating migraine, off-target hepatoxicity and formulation issues have hampered the development for regulatory approval of any therapeutic in this class. The development of monoclonal antibodies to CGRP or its receptor as therapeutic agents has allowed this pathway to be re-investigated. Herein we review why CGRP is an ideal target for the prevention of migraine and describe four monoclonal antibodies against either CGRP or its receptor that are in clinical development for the treatment of both episodic and chronic migraine. We describe what has been publically disclosed about their clinical trials and future clinical development plans.
降钙素基因相关肽(CGRP)是一种经过广泛研究的神经肽,它与偏头痛的病理生理学有关。虽然一些针对CGRP受体的小分子拮抗剂已证明,靶向该途径是治疗偏头痛的一种有效方法,但脱靶肝毒性和制剂问题阻碍了该类任何治疗药物获得监管批准的进程。开发针对CGRP或其受体的单克隆抗体作为治疗药物,使得这一途径能够重新得到研究。在此,我们综述了为什么CGRP是预防偏头痛的理想靶点,并描述了四种针对CGRP或其受体的单克隆抗体,它们正处于治疗发作性和慢性偏头痛的临床开发阶段。我们介绍了关于其临床试验和未来临床开发计划已公开披露的信息。