DOI: 10.1177/03331024261500983 ISSN: 0333-1024

Three-year safety, tolerability, clinical efficacy, and functional outcomes of atogepant for the preventive treatment of migraine: Final results from a phase 3, open-label extension study

Messoud Ashina, Sait Ashina, Cristina Tassorelli, Peter J. Goadsby, Soo-Jin Cho, Rebeka Man, Hua Guo, Eric B. Cohen, Krisztian Nagy, Pranav Gandhi, Jonathan H. Smith
Show PDF Cite

Aim

To report on the three-year safety, tolerability, clinical efficacy, and functional outcomes of atogepant for the preventive treatment of migraine from the phase 3, 156-week, open-label safety extension study in participants with chronic migraine (CM) or episodic migraine (EM) who had a prior inadequate response to two to four classes of conventional oral, non-migraine-specific preventive migraine treatments.

Methods

This was a 156-week, long-term, open-label extension (OLE) safety study in adult participants with either CM or EM who completed the lead-in PROGRESS or ELEVATE trials, respectively. The primary outcome was safety and tolerability of atogepant. Clinical efficacy and functional outcomes were prespecified exploratory analyses. Clinical efficacy endpoints were change from baseline (CFB) in mean monthly migraine days (MMDs), mean monthly headache days (MHDs), mean monthly acute medication use days, and responder rates (CFB ≥ 50%, ≥ 75% or 100% reduction in MMDs). Functional outcomes included CFB in Activity Impairment in Migraine-Diary domain score and Migraine-Specific Quality of Life Questionnaire version 2.1 for 156 weeks. All participants received atogepant 60 mg once daily.

Results

Of 596 participants, 595 (PROGRESS, N  = 325; ELEVATE, N  = 270) were treated and included in the safety population, and 529 (PROGRESS, N  = 285; ELEVATE, N  = 244) were included in the modified intention-to-treat population. The mean duration of atogepant exposure was 808.1 days. Overall, 63.2% (376/595) of participants completed the 3-year open-label treatment period. Treatment-emergent adverse events (TEAEs) occurred in 83.2% (495/595) of participants. Common TEAEs (≥ 10%) were COVID-19 (33.6%, 200/595) and nasopharyngitis (15.5%, 92/595). Serious TEAEs occurred in 8.7% (52/595) of participants, including one death attributed to asphyxia from a house fire, and none were related to atogepant. TEAEs leading to study treatment discontinuation occurred in 6.7% (40/595) of participants. Alanine aminotransferase/aspartate aminotransferase ≥ 3× the upper limit of normal occurred in three participants; none met Hy's Law. Improvements in clinical efficacy and functional outcomes observed during the lead-in studies were maintained through 156 weeks. Post-baseline potentially clinically significant (PCS) weight loss of ≥ 7% from lead-in study baseline at any visit was reported in 37.2% (220/592) of participants, whereas 16.7% (99/592) reported PCS weight gain of ≥ 7%.

Conclusions

In this 3-year OLE study, atogepant was safe and well tolerated over three years for the preventive treatment of migraine in participants with CM and EM who had prior inadequate response to two to four classes of conventional oral, non-migraine-specific preventive migraine treatments. Overall safety results were consistent with the known safety profile of atogepant. No new safety signals were identified. Improvements in clinical efficacy and functional outcomes were maintained through 156 weeks.

Trial Registration

ClinicalTrials.gov NCT04686136; EudraCT Identifier 2020-002470-27.

More from our Archive