ELEVATE Study Highlights Atogepant’s in Patients With Prior Migraine Treatment Failures

In the full dataset of the phase 3 ELEVATE trial (NCT04740827), findings showed that oral atogepant (Qulipta; AbbVie) at 60-mg doses was safe, well tolerated, and effective as a preventive for episodic migraine in those with documented failures of 2 to 4 oral migraine preventive treatment classes.¹

Published in The Lancet Neurology, ELEVATE was the first study of an oral calcitonin gene-related peptide (CGRP) receptor antagonist in this difficult-to-treat population. The trial included 313 participants who received at least 1 dose of either atogepant 60 mg once per day (n = 156) or placebo (n = 157). In the off-treatment hypothetical estimand (OTHE) population (n = 309), which combined the safety population and those with 1 or more of the 4-week post-baseline periods, results at 12 weeks showed a least square mean (LSM) change of –4.2 (SE, 0.4) monthly migraine days with atogepant vs –1.9 (SE, 0.4) on placebo (adjusted P <.0001).

The study was originally presented at the 9th Congress of the European Academy of Neurology (EAN) in July 2023 by lead investigator Cristina Tassorelli, MD, PhD, professor and chair of neurology at the University of Pavia. Atogepant, a high-affinity gepant, has been approved as a preventive for both patients with episodic and chronic migraine. In ELEVATE, most patients (77%) had between 8 and fewer than 15 monthly migraine days. Most participants reported failure by 2 classes of previous preventive treatments (56%), whereas 35% had been failed by 3, and 9% of the cohort had been failed by 4.

Atogepant continued to outperform placebo in a number of secondary outcomes, including reduction of at least 50% in the 3-month average of mean monthly migraine days (51% vs 18%; OR, 4.8; 95% CI, 2.9-8.1; P <.0001) and mean monthly acute medication use days (–3.7 [SE, 0.4] vs –1.1 [SE, 0.4]; P <.0001). The approved treatment also showed significant improvements in the number of patients who had a reduction of at least 25%, 30%, 75%, and 100% in the 3-month average of mean monthly migraine days compared with placebo in the OTHE population and in each 4-week interval during the treatment period.

Authors noted that the shortness of the study was a limitation; however, there is an ongoing open-label extension of ELEVATE (NCT04686136) that will continue to asses atogepant in this refractory population. The study also did not include patients with chronic migraine—those with at least 15 headache days per month—which the authors mentioned as a limitation as well.

"Although 91% to 93% of people with migraine have episodic migraine, those with chronic migraine have higher drug discontinuation rates and cycle through preventive medications more rapidly than those with episodic migraine, which creates a pressing need for effective treatments for chronic migraine in participants with multiple previous preventive treatments," Tassorelli et al wrote.

In terms of safety, 52% of patients on atogepant and 54% of those on placebo experienced treatment-emergent adverse events (TEAEs), most of which were considered mild or moderate in severity. The most common were constipation (atogepant, 10%; placebo, 3%), COVID-19 (atogepant, 8%; placebo: 10%), nausea (atogepant, 7%; placebo, 3%), and nasopharyngitis (atogepant, 5%; placebo, 8%). Severe treatment-emergent adverse events were reported by 1 participant (1%; severe migraine) in the placebo group versus four participants (3%) in the atogepant group (constipation, stage 2 breast cancer, invasive breast carcinoma, and induced abortion). None of these were considered related to the study treatment.

Between the treatment groups, investigators observed no clinically meaningful differences in those with potentially clinically significant blood pressure or pulse rate. Notably, 1 patient on atogepant discontinued treatment following a clinically significant alteration at ECG that was deemed ventricular tachycardia. For hepatic laboratory values, mean baseline to post-baseline changes were small and similar between groups.

Peter J. Goadsby, MD, PhD, DSc, a professor of neurology at both the University of California San Francisco and King’s College, London, sat down with NeurologyLive^® in an interview at the 2023 American Academy of Neurology Annual Meeting to discuss the findings from ELEVATE from a clinical perspective.² In the video below, he talked about the significance of the study, the limitations of the study design, as well as the adverse events of the treatment observed in patients.