Atogepant Sustains 1-Year Efficacy in Migraine in Extension Trial

Messoud Ashina, MD, PhD, DMSc

Results from an open-label extension trial evaluating atogepant 60 mg (Allergan), an orally administered calcitonin gene-related peptide (CGRP) antagonist, showed that the treatment sustained efficacy in reducing monthly migraine days (MMDs), moderate/severe headache days, and acute medication use days over the 1-year study period.¹

Lead author Messoud Ashina, MD, PhD, DMSc, director, Human Migraine Research Unit, Danish Headache Center, and colleagues presented these findings at the 2021 Virtual American Headache Society (AHS) 63rd Annual Scientific Meeting, June 3-6. Participants with 4-14 migraine days per month included in the study were randomized 5:2 to atogepant 60 mg once daily (n = 500) or oral standard of care (n = 200) migraine preventive medication. Eligible participants had completed the phase 2b/3 trial (NCT02848326) or were newly enrolled in the current trial.

From baseline to weeks 1-4, the earliest interval assessed, patients who received atogepant 60 mg had a least-squares (LS) mean change of -3.8 (standard error [SE], 0.1) in MMDs. At the last interval assessed (weeks 49-52), patients in the atogepant group reported a -5.2 (SE, 0.2) LS mean change from baseline MMDs. As for moderate/severe headache days, the data showed a LS mean change of -3.6 (SE, 0.1) from baseline at the earliest interval assessed and continued to show a LS mean change of -4.7 (SE, 0.1) at the last interval assessed.

At 1 year, 84.2% of responders reported at least a 50% reduction in MMDs with treatment with atogepant 60 mg. A reduction of at least 75% in MMDs was reported by 69.6% of responders, while 100% reduction was reported by 48.4% of responders.

The number of monthly acute medication use days was reduced from 6.6 (SE, 3.3) at baseline to 1.7 at 52 weeks with treatment of atogepant 60 mg, equating to a mean change of -4.9 (SE, 0.1) days. Notably, this change was more evident during the earliest interval assessed.

Atogepant has potential to become the next approved treatment on the market following the FDA’s decision to accept its new drug application (NDA) in March 2021.² The regulatory decision, expected to come late in the third quarter of 2021, will be based on supporting evidence from a clinical program that included nearly 2500 patients and spanned across the phase 3 ADVANCE study (NCT02848326), the aforementioned pivotal phase 2b/3 study, and the phase 3 long-term safety study (NCT03777059).

In the ADVANCE study, those treated in the 10-, 30-, and 60-mg arms of atogepant experienced decreases in MMD of 3.69, 3.86, and 4.2 days, respectively, compared with 2.48 days with placebo (all P <.0001) over the 12-week treatment period. ADVANCE included 910 patients, with the efficacy analyses based on the modified intent-to-treat population of 873 patients.³

Lawrence Severt, MD, PhD, director, AbbVie, was among the investigators on ADVANCE, and recently sat down with NeurologyLive to discuss the regulatory outlook of the agent as well as when further action may take place. Listen to his comments below.

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REFERENCES

1. Ashina M, Tepper SJ, Reuter U, et al. Atogepant 60 mg once daily shows efficacy for the preventive treatment of migraine: results from a 52-week open-label extension trial. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract P133

2. US FDA Accepts AbbVie’s new drug application for atogepant for the preventive treatment of migraine. News release. AbbVie. March 30, 2021. Accessed June 3, 2021. https://news.abbvie.com/news/press-releases/us-fda-accepts-abbvies-new-drug-application-for-atogepant-for-preventive-treatment-migraine.htm#:~:text=NORTH%20CHICAGO%2C%20Ill.%2C%20March,antagonist%20(gepant)%2C%20for%20the

3. AbbVie Announces Positive Phase 3 Data for Atogepant in Migraine Prevention. News release. AbbVie. July 29, 2020. Accessed June 3, 2021. news.abbvie.com/news/press-releases/abbvie-announces-positive-phase-3-data-for-atogepant-in-migraine-prevention.htm