The novel, orally administered calcitonin gene-related peptide (CGRP) antagonist atogepant has met the primary endpoint in a Phase 3 trial for migraine prevention, AbbVie, the company developing the drug, has announced.
Topline results from the ADVANCE trial, which evaluated atogepant 10, 30, and 60 mg, showed all three doses were associated with a significant reduction from baseline in mean monthly migraine days compared with placebo.
There were also significant improvements in all six secondary endpoints with the two higher doses.
Data from the ADVANCE trial and a previous Phase 2/3 trial will be the basis for regulatory submissions in the United States and other countries, AbbVie reported.
Decreased Migraine Days
The Phase 3, 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 who experienced 4 to 14 migraine days per month.
A total of 910 patients were randomized to one of four treatment groups: 10 mg, 30 mg, or 60 mg of atogepant once daily or placebo. Efficacy analyses were based on the modified intent-to-treat population of 873 patients.
The primary endpoint was change from baseline in mean monthly migraine days during the 12-week treatment period. All atogepant dose groups met the primary endpoint and demonstrated significantly greater decreases in mean monthly migraine days compared with placebo.
Mean monthly migraine days were reduced by 3.69 days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose of atogepant compared with a reduction of 2.48 migraine days in the placebo group (P < .0001, all dose groups vs placebo).
A key secondary endpoint measured the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days over 12 weeks.
This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group, compared with 29% of the placebo group (P < .0001, all dose groups vs placebo).
Additional secondary endpoints measured during the 12-week treatment period 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 on 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.
Treatment with the 30-mg and 60-mg doses resulted in significant improvements in all secondary endpoints, and treatment with the 10-mg dose resulted in significant improvements in four of the six secondary endpoints.
No new safety risks were observed compared with the safety profile of atogepant observed in previous trials, AbbVie said.
Serious adverse events occurred in 0.9% of patients in the atogepant 10-mg group vs 0.9% of patients in the placebo group. No patients in the atogepant 30-mg or 60-mg groups experienced a serious adverse event.
The most common adverse events (reported in at least 5% of patients and at least one atogepant group, and at a rate greater than placebo), across all doses versus placebo, were constipation (6.9-7.7% vs 0.5%), nausea (4.4-6.1% vs 1.8%), and upper respiratory tract infection (3.9-5.7% vs 4.5%).
Most 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 the trial.
Full data results will be presented at an upcoming medical congress and/or published in a peer-reviewed journal, the company said.
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Cite this: Positive Phase 3 Topline Results for Migraine Prevention Drug - Medscape - Jul 30, 2020.