Promise and Challenges of Targeting PACAP to Treat Migraine: Michael Marmura, MD

WATCH TIME: 3 minutes

"PACAP may offer hope for patients who haven’t responded to other treatments—but we need larger studies to prove it’s safe and effective."

The migraine treatment landscape exploded several years ago with the emergence of calcitonin gene-related peptide (CGRP)-targeting therapies, the first class of agents that directly work on the underlying process of migraine. Research had shown that the infusion of CGRP can induce migraine-like attacks in patients with migraine. By all accounts, these agents were considered a major step up from previously approved therapies, with enhanced efficacy and safety data to support.

Years later, the field is still in search of new treatment pathways for patients who struggle to control their migraine despite being on high-efficacy therapies. One emerging concept has been to target pituitary adenylate cyclase-activating polypeptide, a neuropeptide that has been linked to migraine pathogenesis. As with CGRP, elevated plasma PACAP levels during migraine have been reported, but not consistently observed and infusion of either the PACAP-38 or PACAP-27 isoforms caused migraine in patients. To date, there are a handful of agents advancing their way through the pipeline, including Lundbeck’s Lu AG09222, which is currently being studied in a large-scale phase 2 trial.

Despite the promise behind PACAP, there are several questions about its role and which patients may be more likely to benefit from it. Jefferson Health’s Michael Marmura, MD, recently sat down with NeurologyLive® to discuss the evolving migraine treatment landscape and PACAP as one of the more encouraging new targets. Marmura, director of outpatient care at Jefferson Headache Center, provided clinical context on the current unanswered questions behind this pathway, including some of the larger safety concerns. He also spoke on about what excites him ahead of the upcoming American Headache Society (AHS) Annual Meeting, set to take place June 19-22 in Minneapolis, Minnesota.