The phase 3 ADVANCE trial evaluating the investigational medicine Atogepant, an orally administered calcitonin gene-related peptide ( CGRP ) receptor antagonist ( gepant ) has met its primary endpoint of statistically significantly greater reduction in mean monthly migraine days, compared to placebo, for all doses across the 12-week treatment period.
The pivotal multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the efficacy, safety, and tolerability of oral Atogepant for the prevention of migraine in those with 4 to 14 migraine days per month.
A total of 910 patients were randomized to one of four treatment groups evaluating 10 mg, 30 mg, or 60 mg of Atogepant once daily, or placebo.
Efficacy analyses were based on the modified intent-to-treat ( mITT ) population of 873 patients.
The primary endpoint 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 significantly greater decreases in mean monthly migraine days compared to placebo.
Patients treated in the 10 mg / 30 mg / 60 mg Atogepant arms experienced a decrease of 3.69 / 3.86 / 4.2 days, respectively, all compared to patients in the placebo arm, who experienced a decrease of 2.48 days ( all dose groups vs. placebo, p= less than 0.0001 ).
A key secondary endpoint measured the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across the 12-week treatment period.
The trial demonstrated that 55.6% / 58.7% / 60.8% of patients in the 10 mg / 30 mg / 60 mg Atogepant arms, respectively, achieved at least a 50% reduction, compared to 29.0% of patients in the placebo arm ( all dose groups versus placebo, p= less than 0.0001 ).
Additional secondary endpoints measured across the 12-week treatment period included change from baseline in mean monthly headache days, mean monthly acute-medication use days, and mean monthly performance of daily activities and physical impairment domain scores of the Activity Impairment in Migraine-Diary ( AIM-D ), and change from baseline in the Migraine-Specific Quality of Life Questionnaire ( MSQ ) Role Function-Restrictive domain score at week 12.
The trial has demonstrated that treatment with 30 mg and 60 mg doses resulted in statistically significant improvements in all secondary endpoints, while treatment with the 10 mg dose resulted in statistically significant improvements in four out of the six secondary endpoints.
No new safety risks were observed compared to the safety profile observed in the previous trial evaluating Atogepant.
Serious adverse events occurred in 0.9% of patients treated in the Atogepant 10 mg arm compared to 0.9% of patients in the placebo arm.
No patients in the Atogepant 30 mg or 60 mg treatment arms experienced a serious adverse event.
The most common adverse events reported with a frequency greater than or equal to 5% in at least one Atogepant treatment arm, and greater than placebo, were constipation ( 6.9-7.7% across all doses vs. 0.5% for placebo ), nausea ( 4.4-6.1% across all doses vs 1.8% for placebo ), and upper respiratory tract infection ( 3.9-5.7% across all doses vs 4.5% for placebo ). The majority of cases of constipation, nausea and upper respiratory tract infection were mild or moderate in severity and did not lead to discontinuation.
There were no hepatic safety issues identified in this trial.
Migraine is a complex, chronic disease with episodic attacks that are often incapacitating and characterized by headache pain as well as neurologic and autonomic symptoms.
It is highly prevalent, affecting more than one billion people worldwide, and is the highest cause of disability worldwide for people under 50 years of age.
Due to the unpredictability and fluctuation of attack frequency and severity, migraine has substantial impact on many aspects of an individual's life both during and between attacks. Daily activities, work, school, and personal relationships are negatively affected, leading to a significant burden on the person with migraine, their family, and friends, and often extending to employers and healthcare systems. ( Xagena )
Source: Abbvie, 2020