New Migraine Drug

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.


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.

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).


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.