Atogepant Maintains Long-Term Safety and Efficacy in Migraine Prevention

Atogepant maintains safety, efficacy, and functional benefits over 1 year in patients with chronic migraine (CM) and in those with episodic migraine (EM), according to results from a long-term phase 3 study published in Cephalalgia.

Atogepant is an oral calcitonin gene-related peptide receptor antagonist. Researchers evaluated interim outcomes from a 156-week, open-label safety extension trial (ClinicalTrials.gov Identifier: NCT04686136) that included completers of the PROGRESS trial (ClinicalTrials.gov Identifier: NCT03855137) of atogepant in CM, and the ELEVATE trial (ClinicalTrials.gov Identifier: NCT04740827) of atogepant in EM with prior preventive treatment failures. Participants treated with atogepant were assessed for safety, tolerability, migraine frequency, and patient-reported functional outcomes.

A total of 595 participants were treated with 60 mg atogepant once daily, of whom 325 had CM and 270 had EM. Participants were predominantly women (87.7%) and predominantly White (84.0%), with a mean (SD) age of 42.2 (11.8) years. Mean (SD) treatment exposure was 496.5 (224.7) days.

At the time of analysis, 26.4% of participants had discontinued treatment, most commonly due to participant withdrawal (9.7%) or adverse events (7.1%). Treatment discontinuation due to lack of efficacy occurred in only 2%.

Treatment-emergent adverse events (TEAEs) were reported in 79.0% of participants, most frequently COVID-19 (28.7%), nasopharyngitis (10.9%), and constipation (8.2%). Most adverse events were mild to moderate, though 5.9% discontinued due to TEAEs. Serious TEAEs occurred in 5.5% of participants, with none considered related to atogepant.

Laboratory and vital sign monitoring showed no new safety signals. Clinically significant post-baseline weight loss (≥7%) occurred in one-third of participants, consistent with prior reports of modest weight reduction associated with atogepant use. No participant met Hy’s law criteria for drug-induced liver injury.

Participants experienced a mean reduction of 8.5 (95% CI, -9.0 to -8.0) monthly migraine days at weeks 13 to 16, which was maintained through week 48. Similarly, at weeks 13 to 16, and maintained up to 48 weeks, 70% achieved an equal to or greater than 50% reduction in monthly migraine days. Meanwhile, 43.9% and 18.1% of participants achieved at least 75% and 100% reductions, respectively. Reductions were consistent across both CM and EM cohorts.

Functional outcomes, assessed using the Activity Impairment in Migraine-Diary and the Migraine-Specific Quality of Life Questionnaire v2.1, also showed improvements, sustained through week 52. Patients reported reduced physical impairment and improved ability to perform daily activities, with benefits persisting through week 48.

This study was limited by its open-label design, a predominantly female and White population, exclusion of certain comorbidities, and interim data with long-term outcomes beyond 52 weeks yet to be confirmed.

“The results from this interim analysis support the use of once daily oral atogepant as a long-term preventive treatment across the migraine episodic to chronic spectrum,” the study authors concluded.

Disclosures: This research was supported by AbbVie. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.