No New Safety Signals Seen With Migraine Prevention Drug

DENVER — No new safety signals emerged with daily atogepant (Qulipta) for migraine prevention, an interim analysis of a long-term safety extension study showed, and improvements in efficacy were sustained.

After an average exposure to atogepant of about 500 days, treatment-emergent adverse events occurred in 79% of migraineurs, but most were mild or moderate and not related to atogepant, reported Sait Ashina, MD, of Beth Israel Deaconess Medical Center in Boston, at a late-breaking session at the American Academy of Neurology annual meeting.

Common adverse events that occurred in at least 5% of participants were COVID-19 (28.7%), nasopharyngitis (10.9%), and constipation (8.2%).

“The overall safety results were consistent with the known safety profile of atogepant in episodic migraine and chronic migraine,” Ashina said. “No new safety signals were identified at the interim analysis when atogepant 60 mg was administered once daily for over 48 weeks.”

Atogepant is an oral calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) approved for both episodic migraine and chronic migraine prevention. CGRP, a very potent vasodilator peptide, is thought to be involved in migraine.

Unlike injectable anti-CGRP monoclonal antibodies that have been approved for migraine prevention — erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality), and eptinezumab (Vyepti) — atogepant and other gepants are small-molecule drugs that can be taken orally.

“Gepants, CGRP receptor antagonists, have changed the treatment landscape of migraine by making treatment simple and accessible,” noted headache researcher Peter Goadsby, MBBS, of King’s College London in England.

“Atogepant is well effective and well tolerated long-term, as the new data show,” he told MedPage Today. “Taken once a day, patients can resume a normal life with no side-effect penalty, often after years of disabling migraine.”

The long-term safety study followed participants from two randomized placebo-controlled phase III trials, ELEVATE and PROGRESS. ELEVATE evaluated atogepant for episodic migraine prevention in people who had an inadequate response to 2 to 4 classes of conventional oral migraine prevention drugs. PROGRESS assessed atogepant for preventive treatment of chronic migraine.

Episodic migraine was defined in ELEVATE as 4 to 14 monthly migraine days at baseline; chronic migraine was defined in PROGRESS as 15 days or more. “The baseline monthly migraine days were 19.2 in PROGRESS, 9.1 in ELEVATE, and 14.5 for the total population,” Ashina said.

The interim analysis was conducted at week 48 of the open-label, 156-week safety extension study and included 595 participants: 270 from ELEVATE and 325 from PROGRESS. Mean age was about 42 and 87.7% were women.

Treatment-emergent adverse events that led to discontinuation occurred in 5.9% of participants. Elevated alanine transaminase/aspartate transaminase (ALT/AST) occurred in two participants. The only serious treatment-related adverse event reported by more than one participant was ovarian cyst (one participant each from ELEVATE and PROGRESS).

The mean change from baseline in monthly migraine days was -5.5 in ELEVATE and -10.9 in PROGRESS at weeks 13-16, which was consistent over 48 weeks, Ashina said. “Around 70% had a reduction in headache frequency of at least 50%,” he added.

“This is the first report of 1-year data for chronic migraine, and it extends previous data for 1 year of atogepant data in episodic migraine,” Ashina said. “It’s very encouraging for clinicians, suggesting that atogepant is not only safe for at least 1 year but can also be considered for long-term prevention of migraine.”

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