Atogepant cuts monthly migraine days in OLE trial.An open-label extension (OLE) study demonstrates the long-term safety, tolerability, and efficacy of atogepant for migraine prevention.
“This is the first 3-year report of atogepant treatment in the chronic migraine (CM) population, as well as in episodic migraine (EM) patients who have previously failed conventional oral preventive therapies,” said Dr Jonathan Smith from AbbVie, North Chicago, Illinois, US, at AAN 2026.
This extension study included adults with at least a 1-year history of migraine who had completed the lead-in phase III PROGRESS or ELEVATE trials evaluating atogepant 60 mg QD for the prevention of CM (PROGRESS) or EM (ELEVATE). PROGRESS completers had ≥15 monthly headache days (MHDs), whereas ELEVATE completers had 4–14 monthly migraine days (MMDs).
The safety cohort included 595 participants, while the modified intention-to-treat (mITT) population comprised 529. The mean age was 42.2 years, 87.7 percent were women, and 11.4 percent were from East Asia. Sixty-three percent of the overall cohort completed the 3-year treatment period. The mean duration of atogepant exposure was 808.1 days. [Smith, et al, AAN 2026]
In the overall safety cohort, 83.2 percent of participants reported treatment-emergent adverse events (TEAEs). Seventy-seven percent of these events were mild to moderate in severity and were unrelated to the study drug as evaluated by the investigator. The rate of serious TEAEs was 8.7 percent, but none were related to atogepant. Approximately 7 percent of participants discontinued the study due to TEAEs.
The most common TEAEs were COVID-19 (33.6 percent), nasopharyngitis (15.5 percent), and constipation (8.9 percent).
Three participants had ALT/AST* ≥3 x ULN. Although one case was deemed potentially related to atogepant, this was mild and nonserious.
“Importantly, there was not even a single case of potential Hy’s law or drug-induced liver injury,” Smith said. “The safety profile in this OLE was consistent with the known safety profile of atogepant. No new safety signals were observed.”
From the lead-in study baseline of 14.5 MMDs, the least squares mean change in MMD was –8.2. There were similar improvements for MHDs and monthly acute medication use days.
Approximately 70 percent of the mITT cohort achieved a ≥50-percent reduction in MMDs at week 13–16, and this reduction was sustained over 156 weeks.
“Overall, a favourable efficacy was observed as early as week 13–16, and this was consistently observed throughout the 3 years of treatment,” Smith said.
Given evidence showing modest dose- and duration-dependent weight loss with atogepant, researchers conducted a post hoc analysis using 1-year interim data of OLE participants with overweight or obesity at lead-in baseline. Of the safety analysis participants, 279 met the BMI criteria (mean age 42.8 years, 83.2 percent women). [Peterlin, et al, AAN 2026]
At baseline, the mean weight was 85.6 kg, and the mean BMI was 30.3 kg/m². Sixty percent of participants were classified as overweight; the rest were obese class I. Approximately 63 percent had ≥2 cardiovascular (CV) risk factors, the most common being hypertension (54.8 percent), followed by dyslipidaemia (10.4 percent).
At week 52, the mean weight dropped by 3.44 kg (0.95 kg loss as early as week 4), 34.9 percent of participants experienced a ≥5-percent weight reduction (mean loss, 10 kg), and 12.8 percent had a ≥10-percent weight reduction (mean loss, 16.49 kg).
Weight-related TEAEs occurred in 1.8 percent of participants. There were reports of abnormal weight loss and gain, but the rates were low (0.4 percent each), were nonserious, and did not lead to discontinuation.
“In this migraine subgroup with CV risk factors, a clinically meaningful weight loss was observed with atogepant 60 mg QD throughout 1 year of open-label treatment,” the investigators said.