Phase 4 THRIVE Data Highlights Eptinezumab’s Impact on Migraine After Prior CGRP Failure

Most adults with migraine who had an inadequate response to a prior calcitonin gene related peptide (CGRP)-targeting preventive therapy reported meaningful improvement after switching to eptinezumab (Vyepti), according to headline results from the phase 4 THRIVE trial (NCT06701526). Lundbeck, which markets eptinezumab, announced that 60% of participants in the open-label trial rated themselves "much improved" or "very much improved" at 24 weeks.¹

“These results provide important prospective clinical trial data for people who continue to experience substantial migraine burden despite treatment with a prior CGRP-targeting preventive therapy,” Tarek Samad, PhD, executive vice president and head of research and development at Lundbeck, said in a statement.¹

THRIVE was an open-label, multicenter, phase 4 trial enrolling 164 adults with 8 or more monthly migraine days who had an inadequate response to 1 prior CGRP-targeting preventive therapy, either a subcutaneous monoclonal antibody or a preventive gepant. Participants received intravenous eptinezumab over 24 weeks; 84% (138 of 164) completed the trial, and 147 received 2 infusions.

The primary endpoint was the proportion of participants reporting being “much improved” or “very much improved” on the 7-point Patient Global Impression of Change scale. That threshold was met by 44% of participants at week 12 and 60% at week 24. Lundbeck said reductions in monthly migraine days, monthly headache days, and acute medication use were also assessed, along with measures of migraine-related burden including the Migraine Disability Assessment Scale, goal attainment, and brain fog, though the press release did not report specific numeric results for those secondary measures.

READ MORE: Migraine Forecasting Model Reaches 91% Precision Using App-Based Headache Data

Eptinezumab was reported as generally well tolerated, with no new safety signals identified in this population. Full results are planned for presentation at a future scientific congress and peer-reviewed publication.

THRIVE's open-label result is consistent with earlier, smaller real-world data. In the INFUSE study, presented at the Headache Cooperative of the Pacific's 2026 annual conference, 111 patients who had failed at least 1 prior anti-CGRP preventive therapy and completed 6 months of eptinezumab treatment showed a mean reduction of 6.8 monthly headache days from a baseline of 20.0 days, with 44.1% reporting being "much improved" or "very much improved" on the same PGIC scale.²

Eptinezumab is a humanized monoclonal antibody that binds circulating calcitonin gene-related peptide (CGRP) and blocks it from binding to its receptor. The FDA approved it in February 2020 as the first and, to date, only intravenously administered preventive migraine therapy in its class, dosed as a 100 mg infusion every 3 months, with some patients receiving 300 mg.³

“VYEPTI is a valuable addition for the treatment of migraine, which can help reduce the burden of this serious disease,” Peter Goadsby, MD, professor of neurology at King's College London and the University of California, San Francisco, said at the time of approval.³

REFERENCES
1. Lundbeck announces headline results from phase IV THRIVE trial evaluating Vyepti (eptinezumab) following inadequate response to prior CGRP-targeting preventive therapy. News release. Published October 1, 2026. Accessed October 6, 2026. https://www.prnewswire.com/news-releases/lundbeck-announces-headline-results-from-phase-iv-thrive-trial-evaluating-vyepti-eptinezumab-following-inadequate-response-to-prior-cgrp-targeting-preventive-therapy-302895545.html
2. Lundbeck presents new real-world data highlighting meaningful improvements in patients severely impacted by migraine initiating Vyepti (eptinezumab), at HCOP Annual Conference. News release. Published January 30, 2026. Accessed October 6, 2026. https://www.prnewswire.com/news-releases/lundbeck-presents-new-real-world-data-highlighting-meaningful-improvements-in-patients-severely-impacted-by-migraine-initiating-vyepti-eptinezumab-at-hcop-annual-conference-302675102.html
3. FDA approves Lundbeck's VYEPTI (eptinezumab-jjmr), the first and only intravenous preventive treatment for migraine. News release. Published February 21, 2020. Accessed October 6, 2026. https://www.businesswire.com/news/home/20200221005507/en/FDA-Approves-Lundbeck%E2%80%99s-VYEPTI%E2%84%A2-eptinezumab-jjmr-%E2%80%93-Intravenous