Atogepant Reduces Monthly Episodic Migraine Days in Phase 3

July 31, 2020

The gepant agent significantly reduced mean monthly migraine days across all 3 doses—10 mg, 30 mg, and 60 mg—compared with placebo over the 12-week treatment period.

Thomas J. Hudson, MD

AbbVie recently announced positive results from the phase 3 ADVANCE clinical trial (NCT02848326) of atogepant in those with episodic migraine, with the agent reporting statistically significant improvements in monthly migraine days (MMD) compared with placebo.1

The small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, or gepant, met the primary end point, with those treated in the 10-, 30-, and 60-mg arms experiencing 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.

The full results of the trial are expected to be presented at an upcoming medical meeting and/or in a peer-reviewed journal, according to AbbVie.

“Migraine attacks can be debilitating, but migraine is a treatable disease, and people living with it are not alone in their battle to control it,” said Thomas J. Hudson, MD, senior vice president, research and development, and chief scientific officer, AbbVie, in a statement. “With the results from these trials, we aim to provide a safe and effective preventive treatment that offers patients and healthcare providers a simple, once daily oral treatment that works specifically by blocking CGRP receptors and preventing migraine.”

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A key secondary end point was the proportion of patients that achieved ≥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. Comparatively, 29.0% of those in the placebo group achieved ≥50% reduction (all P <.0001).

The data showed that treatment with both the 30 mg and 60 mg doses resulted in statistically significant improvements in every secondary end point, while treatment with the 10 mg dose resulted in statistically significant improvements in 4 of 6 end points. Those other secondary end points included change from baseline in mean monthly headache days, mean monthly acute-medication use days, mean monthly performance of daily activities and physical impairment domain scores of the Activity Impairment in Migraine-Diary (AIM-D), as well as change from baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role Function-Restrictive domain score.

Atogepant also 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 ≥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). The majority of cases were deemed mild or moderate in severity and did not lead to discontinuation. No hepatic safety issues were identified.

In June 2020, data presented by K. Chris Min, MD, PhD, at the American Headache Society (AHS) virtual annual scientific meeting suggested that, when administered once daily over the course of 28 days, the use of 170-mg oral atogepant was both safe and well-tolerated, with no evidence of clinically significant drug-related alanine aminotransferase (ALT) elevations in healthy adults. The results showed that by Day 28, the geometric mean fold change in ALT from baseline levels was 0.79 (95% CI, 0.70—0.89) with atogepant compared with 0.99 (95% CI, 0.84–1.17) in the placebo group. Additionally, no ALT elevations ≥3 times the upper limit of normal were observed at any time postdose.2

REFERENCES

1. AbbVie Announces Positive Phase 3 Data for Atogepant in Migraine Prevention. News release. AbbVie. July 29, 2020. Accessed July 30, 2020. news.abbvie.com/news/press-releases/abbvie-announces-positive-phase-3-data-for-atogepant-in-migraine-prevention.htm

2. Min KC, Kraft WK, Bondiskey P, et al. Multiple, Once-daily, Oral Doses of 170 Mg Atogepant for 28 Days Are Safe and Well Tolerated with No Clinically Significant Effect on Alanine Aminotransferase in Healthy Adults. Headache. 2020;60(S1 suppl). 1-156. doi: 10.1111/head.13854