AAN 2026: What Is PACAP and Why Does It Matter for Migraine? Lundbeck's R&D Chief Explains the Science Behind Bocunebart

In an interview with Pharmacy Times at the 2026 American Academy of Neurology (AAN) Annual Meeting, Johan Lutman, executive vice president and head of R&D at Lundbeck, explained that the PACAP pathway represents a meaningful advance beyond CGRP therapies because it is active in both the sensory and parasympathetic nervous systems, offering broader biological targets for migraine prevention.

Lutman outlined bocunebart's clinical development program, which progressed from mechanistic challenge studies in healthy volunteers through the Phase 2a HOPE trial—which demonstrated proof of concept in patients who had failed 2 to 4 prior preventive therapies—to the PROCEED trial, which explored multiple doses and routes of administration, with full results to be presented at the American Headache Society meeting in June 2026.

Pharmacy Times: Can you introduce yourself and explain your current role?

Johan Lutman: Hi, I'm Johan Lutman. I'm Head of R&D and Executive Vice President at a company called Lundbeck, a Danish-headquartered company with a global presence.

Pharmacy Times: What makes the PACAP pathway a meaningful target in migraine beyond what CGRP therapies already address?

Lutman: PACAP—or pituitary adenylate cyclase-activating polypeptide—is a signaling peptide, sometimes called a neuropeptide, that resides in the nervous system. It is particularly relevant in the context of migraine because it co-localizes with another molecule known as CGRP, or calcitonin gene-related peptide, which is the basis of existing migraine drugs. CGRP sits in the sensory nervous system—in the peripheral trigeminal ganglion and other sensory nerve cells. PACAP, however, also sits in the parasympathetic nervous system, the system that regulates blood pressure and other autonomic functions. So it is fundamentally located in pathways involved in signaling into and out of the brain. Biologically, that is very interesting. For a long time, the main known function of PACAP was that it is a potent vasodilator—it increases the diameter of blood vessels. That is where the interest in migraine originated, because CGRP also regulates vasodilation, and there has long been a hypothesis that vasodilation plays a role in migraine pathophysiology. The older triptans also work through a serotonin receptor but with a similar vasodilatory mechanism. CGRP is now a large drug class, with seven approved agents delivering real value for migraine prevention. PACAP represents new biology—there is some overlap with CGRP, but the parasympathetic component adds a broader biological dimension to explore.

Pharmacy Times: What did the Phase 1 co-administration data with a gepant show, and why does that matter clinically?

Lutman: Gepants are small molecules in the CGRP field that block the CGRP receptor. They are well-established treatments for migraine. Because bocunebart targets the PACAP pathway—with one ligand and three receptors—we wanted to ensure there was no clinically meaningful interaction between it and a gepant. Classical drug-drug interaction concerns—such as metabolic inhibition—are very unlikely when combining a small molecule with an antibody, but we wanted to confirm that the two agents are well tolerated together. Gepants are widely used in clinical practice, and if bocunebart is going to be used as an add-on therapy alongside them, we need clear safety and tolerability data to support that. We conducted that study, and we have good data demonstrating that the combination is safe and well tolerated. This was an important Phase 1 study that paves the way to test bocunebart in real-world settings where gepants are already being used.

Pharmacy Times: What do the PROCEED trial results tell us about where bocunebart is headed?

Lutman: Bocunebart has moved through a comprehensive development program. We began classically in Phase 1 with single and multiple ascending dose studies, then moved to a mechanistic challenge study in which we administered PACAP to healthy volunteers followed by the antibody to demonstrate that the drug works in vivo. That study also allowed us to observe vascular physiology that may relate to migraine pathophysiology—a very important phase 1b step. We then advanced to a Phase 2a proof-of-concept trial called HOPE, which enrolled migraine patients who had already failed two to four prior preventive therapies. We tested a high dose and a lower dose to fully probe whether this mechanism can work at all. We were very encouraged to see that the HOPE trial did indeed show that it works—a new mechanism demonstrating efficacy for the first time in over 20 years since CGRP. The PROCEED trial followed, exploring a range of doses, routes of administration, and other variables to build a comprehensive picture of the compound. We are being somewhat guarded about the full data set because it will be presented at the American Headache Society meeting in June. What I can say is that we are now in the process of planning Phase 3 pivotal trials. We are determined that bocunebart has the potential to become another treatment option for patients with severe migraines who are not adequately helped by the drugs we currently have.

Pharmacy Times: How do you see bocunebart and eptinezumab fitting together in the migraine treatment picture?

Lutman: The CGRP drug class—of which eptinezumab is a part—is highly efficacious for many patients, but it is far from helping everyone, and we are talking here about patients with very severe migraines. Many people have experienced an occasional migraine—perhaps triggered by red wine or other factors—and have it a few times a year. Those are not the patients we are primarily targeting. We are targeting those with devastating disease: patients who can have up to one migraine per day, a condition that profoundly affects their ability to pursue education, maintain family life, and sustain quality of life. Patients with episodic or chronic migraine—those having 8, 10, 12, or even 24 or more headache days per month—are the population for whom eptinezumab, our CGRP drug, is indicated. Unfortunately, CGRP therapies do not help everyone, and the remaining unmet need is substantial. Migraine also disproportionately affects women during a critical phase of life—one that shapes educational and family outcomes for decades. A new mechanism that can expand the treatment arsenal for the prevention of migraine is very much needed, and that is what bocunebart aims to provide.