Exploring Synergistic Treatment Strategies for Migraine With Monoclonal Antibodies and Gepants: Stewart J Tepper, MD

WATCH TIME: 5 minutes

“This is very exciting because we do have patients that don't seem to respond to the anti-CGRP drugs and [PACAP] represents a new target. The patients that were involved in this study had between 2 and 4 preventive medications that failed. I look forward to a phase 3 trial with this monoclonal antibody and hope that we have a new target in migraine prevention.”

Lu AG09222 (Lundbeck), a humanized monoclonal antibody, is an intravenously infused agent that binds to a pituitary adenylate cyclase-activating polypeptide (PACAP) ligand with high affinity. This monoclonal antibody prevents PACAP from activating its receptors and also prevents PACAP-induced arterial dilation in humans.¹ Although calcitonin gene-related peptide (CGRP)-targeting therapies are a current standard in the migraine, PACAP has risen as promising neuropeptide involved in the pathophysiology of the condition.

At the recent 2023 International Headache Congress, held September 14-17, in Seoul, Korea, new data from the phase 2 HOPE trial (NCT05133323) highlighted the effects of Lu AG09222, a PACAP-targeting agent, as a potential preventive for migraine.² Additionally, investigators presented data from a double-blind, parallel-group, placebo-controlled, phase 1 trial (NCT049766309) highlighting the ability of Lu AG09222 to inhibit PACAP38-induced cephalic vasodilation.³

Recently, at the 2023 International Congress on the Future of Neurology (IFN) Annual Meeting, held September 22-23, in Jersey City, New Jersey, Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth and director of the Dartmouth Headache Center at Dartmouth Health and Jessica Ailani, MD, FAHS, FAAN, director at MedStar Georgetown Headache Center, presented on comprehensive treatment strategies for migraine in a featured session.

At the meeting, Tepper sat down in an interview with NeurologyLive® to discuss the recent developments and advances in the field of migraine including PACAP. He spoke about how PACAP could be a potential treatment in migraine prevention, especially for patients who are unresponsive to antiCGRP therapies. He talked about the safety implications of using multiple gepants in migraine management, and if this approach should be widely adopted. In addition, Tepper explained the significance of the growing trend of combining monoclonal antibodies and gepants in migraine treatment and shared the key takeaways from these combinations.

Click here for more coverage on IFN 2023.

REFERENCES
1. Lundbeck presents clinical advances in migraine prevention with positive trial results at international headache congress. News release. Lundbeck. September 14, 2023. Accessed September 29, 2023. https://news.cision.com/h--lundbeck-a-s/r/lundbeck-presents-clinical-advances-in-migraine-prevention-with-positive-trial-results-at-internatio,c3835332
2. Ashina M, Phul R, Khodaie M, Florea I. Efficacy and safety of Lu AG09222 for migraine prevention in patients with 2-4 previous preventive treatment failures: HOPE, an interventional, randomized, double-blind, parallel-group, placebo-controlled phase 2 trial. Presented at IHC 2023; September 14-17; Seoul, South Korea.
3. Rasmussen NB, Deligiannia C, Christensen CE, et al. PACAP-targeted antibody Lu AG09222 inhibits vasodilation in healthy volunteers. Presented at IHC 2023; September 14-17; Seoul, South Korea.