FDA Accepts NDA for Migraine Preventive Atogepant


In the phase 3 ADVANCE trial, all active treatment arms of atogepant met their primary end point, and the 30-mg and 60-mg doses met all 6 secondary end points with statistical significance.

Michael Gold, MD

Michael Gold, MD

AbbVie announced today that the FDA has accepted its new drug application (NDA) for its investigational agent atogepant (Allergan) for the preventive treatment of migraine in adults with episodic migraine. A regulatory decision is expected to come late in the third quarter of 2021.1

Atogepant, an orally administered calcitonin gene-related peptide (CGRP), had its NDA supported by a clinical program that included nearly 2500 patients and spanned across the phase 3 ADVANCE study (NCT02848326), the pivotal phase 2b/3 study (NCT0284832), and the phase 3 long-term safety study (NCT03777059).

"We believe atogepant is an advancement with the potential to offer meaningful benefits as a safe, effective oral preventive treatment option. Despite the availability of other migraine treatment options, the medical community and people living with migraine recognize the unmet need of those who face the unpredictable and debilitating realities of this disease,” Michael Gold, MD, vice president, neuroscience department, AbbVie, said in a statement.

The pivotal phase 3 ADVANCE trial met the primary end point, with those treated in the 10-, 30-, and 60-mg arms experiencing decreases in monthly migraine days (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.2

READ MORE: Medication Overuse Headache in Chronic Migraine Linked to High Burden

A key secondary end point was the proportion of patients that achieved greater than 50% reduction in mean MMD across the treatment period. For that end point, 55.6% of patients in the 10-mg arm, 58.7% of patients in the 30-mg arm, and 60.8% of patients in the 60-mg arm achieved that threshold. In comparison, 29.0% of those in the placebo group achieved greater than 50% reduction (all P <.0001).

Atogepant showed a familiar safety profile to what has been observed in its prior trial, with serious adverse events (AEs) occurring in 0.9% of the 10-mg arm, and no serious AEs reported in the 30-mg or 60-mg arms compared with placebo (0.9%).

The most common AEs occurring in greater than 5% of patients and greater than placebo in at least 1 atogepant treatment arm were constipation (6.9% to 7.7% across all doses; 0.5% for placebo), nausea (4.4% to 6.1% across all doses; 1.8% for placebo), and upper respiratory tract infection (3.9% to 5.7% across all doses; 4.5% for placebo).

Findings from the phase 2b/3 study evaluating the long-term safety and tolerability of atogepant were presented at the 2019 American Headache Society (AHS) Annual Meeting, July 11–14, 2019, in Philadelphia, Pennsylvania.3 In that study, at the lowest dose of atogepant administered (10 mg once daily [QD], n = 92), there was a 4.00-day reduction in mean MMD compared with a reduction of 2.85 days in the placebo arm (adjusted P = .0236). This benefit remained consistent across 5 doses of atogepant explored in the study. At the largest dose (60 mg twice daily [BID], n = 87), there was a 4.14-day mean reduction in monthly migraine days (adjusted P = .0031).

Atogepant was examined across a variety of doses with each compared with placebo during a 12-week double-blind treatment period that was followed by a 4-week safety evaluation. The doses examined were 10 mg QD (n = 92), 30 mg QD (n = 182), 60 mg QD (n = 177), 30 mg BID (n = 79), and 60 mg BID (n = 87). There were 178 patients in the placebo group.

The phase 3 long-term safety study is a randomized, open-label study that evaluated the safety and tolerability of 60 mg oral atogepant administered daily over 52 weeks for the preventive treatment of migraine in adults with 4 to 14 migraine days per month. Further details on the study will be presented at the upcoming American Academy of Neurology Virtual Annual Meeting.1

1. US FDA Accepts AbbVie’s new drug application for atogepant for the preventive treatment of migraine. News release. AbbVie. March 30, 2021. Accessed March 30, 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
2. AbbVie Announces Positive Phase 3 Data for Atogepant in Migraine Prevention. News release. AbbVie. July 29, 2020. Accessed March 30, 2021. news.abbvie.com/news/press-releases/abbvie-announces-positive-phase-3-data-for-atogepant-in-migraine-prevention.htm
3. Goadsby PJ, Dodick DW, Ailani J, et al. Orally administered atogepant was efficacious, safe, and tolerable for the prevention of migraine: results from a phase 2b/3 study. Presented at: American Headache Society 2019, Philadelphia, PA, July 11-14, 2019.
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