Galcanezumab Anti-calcitonin gene-related peptide (CGRP) MAb Treatment for migraine Treatment for cluster headache

摘要

Calcitonin gene-related peptide (CGRP), a potent vasodilator and neuropeptide, has long been implicated in the etiology of migraine, although the site of action for CGRP in migraine development remains a topic of debate. Inhibition of CGRP with orally available small-molecule drugs has proven efficacious in reducing the severity and frequency of migraines in clinical trials. However, concerns regarding toxicities led to the development of anti-CGRP antibodies. Galcanezumab is a fully humanized anti-CGRP antibody that has linear pharmacokinetics and elicits rapid and sustained suppression of CGRP-mediated changes in capsaicin-induced dermal blood flow in humans and monkeys. In humans, the drug has a half-life of 25-30 days, facilitating once-monthly subcutaneous dosing. Clinical studies have indicated that the drug has low immunogenicity and is well tolerated, with no treatment-related serious adverse events. The most common adverse events reported in migraineurs have been injection-site reactions, upper respiratory tract infections and abdominal pain. In phase II trials in patients with episodic migraine, galcanezumab significantly reduced the number of migraine headache days per 28 days when compared with placebo. Several phase III studies of galcanezumab in patients with episodic or chronic migraine and cluster headaches are ongoing.