Gepant sNDA for Chronic Migraine: Atogepant from AbbVie

The selection of treatments for migraine headache may expand again shortly based on the recent announcement by AbbVie of its submission to the US Food and Drug Administration (FDA) of a supplemental new drug application (sNDA) for atogepant to support treatment of chronic migraine in adults.

Atogepant, an oral calcitonin gene-related peptide (CGRP) antagonist (gepant), is the only oral gepant developed specifically for prevention of migraine and was approved for prevention of episodic migraine in September 2021.

Approval of the sNDA would make atogepant the first agent in the class with a broad preventive treatment indication comprising both episodic and chronic migraine.

“Having one oral medication to treat both episodic and chronic migraine would be an important advancement for health care providers and patients,” said AbbVie neuroscience development therapeutic area head Michael Gold, in the AbbVie announcement. "No two migraine patients are alike, so having multiple treatment options with unique mechanisms of action is critical,” he added.

The sNDA submission is based on data from the pivotal phase 3 PROGRESS clinical trial which evaluated the safety, efficacy, and tolerability of atogepant for prevention of chronic migraine, defined as headaches for 15 or more days per month, which, on at least 8 of those days per month, have the features of migraine, according to investigators.

Participants in PROGRESS had a diagnosis of chronic migraine for at least one year.

The study’s primary endpoint measured reduction from baseline in mean monthly migraine days vs placebo for 2 doses, 60 mg once daily and 30 mg twice daily, across a 12-week treatment period.2

Key secondary endpoints were:

• Change from baseline in mean monthly headache days
• Change from baseline in mean monthly acute medication use days a
• Proportion of participants with at least a 50% reduction in mean monthly migraine days
• Change from baseline in MSQ v2.1 Role Function-Restrictive domain score (migraine impact and degree of impact on daily activities and on emotional function)

The PROGRESS trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days vs placebo ross the 12-week treatment period in adults with chronic migraine, according to AbbVie.

PROGRESS investigators also reported treatment with atogepant 60 mg once daily and 30 mg daily statistically significantly improved measures of all 6 secondary endpoints.

The study’s overall safety profile was consistent with the safety findings seen in previous studies in a population with episodic migraine, with the most common adverse events being constipation and nausea.