Real-World Effectiveness of Eptinezumab After CGRP Preventive Failure: Amaal Starling, MD, FAHS, FAAN

WATCH TIME: 5 minutes | Captions are auto-generated and may contain errors.

“This was a population with a very high burden of disease and multiple prior CGRP failures, yet we still saw early and sustained benefit. The consistency we observe with intravenous administration may help explain why some patients respond even after other CGRP-targeted therapies were ineffective.”

The growth of calcitonin gene–related peptide (CGRP)-targeted therapies has significantly expanded preventive options for migraine. Yet many patients continue to experience substantial disease burden despite prior exposure to monoclonal antibodies or oral gepants. As clinicians consider treatment sequencing within this class, real-world evidence evaluating outcomes after prior CGRP failure has become increasingly important.

At the 2026 Headache Cooperative of the Pacific (HCOP) Annual Conference, 6-month results from the ongoing INFUSE study assessed intravenous eptinezumab (Vyepti; Lundbeck) in adults with migraine who had failed at least one prior CGRP-targeted preventive therapy. This prospective U.S. observational study included participants who completed two infusions over 6 months (n = 111). The cohort reflected a high-burden population, with a mean baseline of 20 monthly headache days, and more than half had previously failed three or more CGRP-targeted preventives.

After six months, 44.1% of participants achieved at least a 50% reduction in monthly headache days, with a mean reduction of 6.8 days. Additionally, 26.1% achieved more than a 75% reduction. Patient-centered outcomes were similarly notable, including an average increase of 6.3 additional “good days” per month and favorable Patient Global Impression of Change responses. While safety data were not collected in this observational analysis, prior phase 3 trials such as PROMISE-1 and PROMISE-2 have demonstrated a favorable tolerability profile.^1,2

Following the presentation, Amaal Starling, MD, FAHS, FAAN, associate professor of neurology at Mayo Clinic College of Medicine, sat down with NeurologyLive^® to discuss how clinicians should interpret these findings in a treatment-experienced population. In the discussion, she outlined potential reasons for response despite prior CGRP failure, including the pharmacokinetic advantages of intravenous administration, and explained how these data may inform real-world migraine management decisions.

REFERENCES
1. Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97(2):553-622. doi:10.1152/physrev.00034.2015
2. INFUSE Study Data Presented at the 2026 Headache Cooperative of the Pacific Annual Conference. Lundbeck Press Release. January 30, 2026.