Walter Sarah, Bigal Marcelo E
Migraine & Headache, Clinical Development, Global Branded R&D, Teva Pharmaceuticals, 41 Moores Road, Frazer, PA, 19355, USA.
Curr Pain Headache Rep. 2015 Mar;19(3):6. doi: 10.1007/s11916-015-0476-1.
Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide whose involvement in migraine pathophysiology is well established. Originally migraine was believed to be a disease of the vasculature, but research has highlighted this to be a disease of the brain with CGRP playing an important role. While targeting CGRP using small molecule antagonists against the receptor has been effective, long-term use of these agents has not been possible due to safety concerns and/or formulation challenges. Recent advances in therapeutic antibodies have opened up new possibilities for treatment of migraine. TEV-48125 is one of four monoclonal antibodies targeting CGRP or its receptors, currently in development for the preventive treatment of migraine. This article discusses the in vitro and in vivo pharmacology of TEV-48125 as well as highlighting its safety profile through the six Phase 1 studies that have been conducted. Finally, the current state of development and future studies for TEV-48125 will be reviewed.
降钙素基因相关肽（CGRP）是一种由37个氨基酸组成的神经肽，其在偏头痛病理生理学中的作用已得到充分证实。最初，偏头痛被认为是一种血管疾病，但研究表明这是一种脑部疾病，CGRP在其中起着重要作用。虽然使用针对该受体的小分子拮抗剂靶向CGRP已被证明有效，但由于安全问题和/或制剂挑战，这些药物无法长期使用。治疗性抗体的最新进展为偏头痛的治疗开辟了新的可能性。TEV-48125是四种靶向CGRP或其受体的单克隆抗体之一，目前正处于偏头痛预防性治疗的研发阶段。本文讨论了TEV-48125的体外和体内药理学，并通过已进行的六项1期研究突出了其安全性。最后，将回顾TEV-48125的当前研发状态和未来研究方向。
