PACAP and migraine.

A number of neuropeptides, including pituitary adenylate cyclase-activating polypeptide (PACAP), play an important role in the pathophysiology of migraine. Infusions of PACAP in patients with migraine can provoke migraine attacks. A placebo-controlled study with a monoclonal antibody directed against the PACAP-receptor failed to show efficacy. In a small, short, proof-of-concept study, a monoclonal antibody directed against PACAP (Lu AG09222) showed efficacy in reducing monthly migraine days compared to placebo but failed for the end point 50% reduction in migraine days. The ongoing PROCEED study, a double-blind, placebo-controlled, dose-finding study investigating four different doses of Lu AG09222 versus placebo for migraine prevention, is expected to complete in the second half of 2025.