New long-term data confirm safety, efficacy of atogepant for migraine prevention

Daily use of the oral calcitonin gene-related peptide (CGRP) receptor antagonist atogepant to prevent migraine is associated with a favourable safety profile and sustained improvements in efficacy outcomes, according to the 52-week data from an ongoing, open-label, 156-week safety extension study.

Treatment-emergent adverse events (TEAEs) occurred in 79.0 percent of participants after taking atogepant 60 mg once daily for a mean of 496.5 days, but most of these TEAEs (94.2 percent) were mild-to-moderate in severity and not related to the study drug, reported first study author Dr Sait Ashina of BIDMC Comprehensive Headache Center, Beth Israel Deaconess Medical Center in Boston, Massachusetts, US.

Common TEAEs reported in at least 5 percent of participants were COVID-19 (28.7 percent), nasopharyngitis (10.9 percent), and constipation (8.2 percent). TEAEs led to treatment discontinuation in 5.9 percent of participants. There were 5.5 percent of participants who experienced serious TEAEs, which were likewise deemed unrelated to atogepant.  [AAN 2024, abstract 006]

Meanwhile, none of the participants met the criteria for Hy’s Law. There were two cases of alanine aminotransferase/aspartate transaminase elevations of at least thrice the upper limit of normal, with one of them considered to be possibly related to atogepant treatment. One death attributed to asphyxia by housefire was documented.

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

The safety analysis included 595 participants (mean age 42.2 years, 87.7 percent female). Of these, 270 had previously taken two to four classes of preventive drugs for episodic migraine with no success and had participated in the phase III ELEVATE trial of atogepant. The remaining 235 had chronic migraine and had participated in the phase III PROGRESS trial of the CGRP receptor antagonist.

Of the participants, 64.5 percent were from Europe, 24.0 percent were from North America, and 11.4 percent were from East Asia. The lead-in study baseline number of migraine days per month was 9.1 for ELEVATE participants, 19.2 for PROGRESS participants, and 14.5 for the overall population.

“Some participants had a gap between the lead-in study and open-label extension during which they were off atogepant treatment,” Ashina said.

Durable efficacy

At 13–16 weeks, monthly migraine days decreased by 5.5 for ELEVATE participants, 10.9 for PROGRESS participants, and 8.5 for the overall population, with a ≥50-percent reduction achieved in 73.5 percent, 67.0 percent, and 70.0 percent of participants, respectively. This improvement, according to Ashina, was consistent over 48 weeks.

Atogepant also extended its beneficial effects on headache days and use of acute migraine medications, with reductions comparable to that observed for migraine days. This benefit was seen regardless of whether the participants received atogepant or placebo in the lead-in studies, Ashina added.

The modified intention-to-treat analysis included 524 participants, of which 240 were from ELEVATE and 284 were from PROGRESS.  

“This is the first report of 1-year atogepant data in the chronic migraine population and extends previously observed 1-year atogepant data in episodic migraine to include the preventive treatment failure population,” Ashina pointed out.

“It is 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,” he concluded.