Atogepant significantly reduces migraines, shows study

AbbVie have announced the 12-week results from Phase III ADVANCE trial evaluating atogepant for the preventive treatment of migraine in adults who meet the criteria for episodic migraine.

Atogepant is an investigational orally administered calcitonin gene-related peptide (CGRP) receptor antagonist (gepant), which, if approved, will be the first and only oral gepant specifically developed for the preventive treatment of episodic migraine. It is currently under review by the US Food and Drug Administration (FDA),

The pivotal Phase III, multi-centre, randomised, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the efficacy, safety and tolerability of oral atogepant for the preventive treatment of migraine in those with four to 14 migraine days per month. A total of 910 patients were randomised to one of four treatment groups evaluating 10mg, 30mg and 60mg of atogepant once daily, or placebo. Efficacy analyses were based on the modified intent-to-treat (mITT) population of 873 patients.

The primary endpoint for the ADVANCE trial was change from baseline in mean monthly migraine days across the 12-week treatment period. All atogepant dose groups met the primary endpoint and demonstrated statistically significant reductions in mean monthly migraine days compared to placebo. Patients treated in the 10mg, 30mg and 60mg atogepant arms experienced a decrease of 3.7, 3.9 and 4.2 days, respectively, compared to patients in the placebo arm, who experienced a decrease of 2.5 days. 

Efficacy results for pre-specified, multiplicity-controlled secondary endpoints in the ADVANCE trial across the 12-week treatment period included:

• A significantly greater reduction from baseline in acute medication use days was seen with all doses of atogepant compared to placebo, with a decrease of 3.7, 3.7 and 3.9 days for the 10mg, 30mg and 60mg doses, respectively, compared to a 2.4-day decrease with placebo.
• The trial demonstrated that 55.6 percent, 58.7 percent and 60.8 percent of patients in the 10mg, 30mg and 60mg atogepant arms, respectively, achieved a 50.0 percent or greater reduction in monthly migraine days, compared to 29.0 percent of patients in the placebo arm.
• Improvements in the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1) Role Function-Restrictive domain score were significantly greater with atogepant at all doses, compared to placebo at week 12.
• Significant greater improvements in the mean monthly AIM-D Performance of Daily Activities domain score compared to placebo were observed for the 30mg and 60mg doses, -2.5 points for the 30mg dose, and -3.3 points for the 60mg dose.
• The Physical Impairment domain in the AIM-D score showed statistically greater improvement for the 30mg and 60mg doses of atogepant compared to placebo, -2.0 for the 30mg dose and -2.5 for the 60mg dose.

All doses were well tolerated. The most common adverse events (AEs) reported with a frequency of five percent or more in at least one atogepant treatment arm, and greater than placebo, were constipation, nausea and upper respiratory tract infection. The majority of these cases were mild or moderate in severity and did not lead to discontinuation.

The findings were published in NEJM.