63 - Long-term Cardiovascular Safety of Lasmiditan for the Acute Treatment of Migraine For Up to One Year: Interim Results of an Open-Label Phase 3 Study (GLADIATOR)

¹Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University, Hempstead, USA. ²Harvard Medical School, Boston, USA. ³Eli Lilly and Company, Indianapolis, USA

Purpose
Lasmiditan, a selective serotonin (5-HT) 1F receptor agonist, lacks the vasoconstrictive activity of other acute migraine treatments. Previous studies of lasmiditan for the acute treatment of a single migraine attack demonstrated that the drug has a low risk of associated cardiovascular (CV) treatment-emergent adverse events (TEAEs), with no difference in the frequency of CV TEAEs between subjects with and without CV risk factors. The long-term CV safety of lasmiditan for the acute treatment of migraine for up to 1 year was assessed by analyzing interim results from the Phase 3 study GLADIATOR.
Methods
In GLADIATOR (NCT02565186), patients who previously participated in Phase 3, placebo-controlled, single-attack lasmiditan studies (SAMURAI, NCT02439320; SPARTAN, NCT02605174) were randomized 1:1 to open-label lasmiditan 100 or 200 mg taken as one dose (within 4 hours of the onset of moderate or severe pain) or, if needed, two doses (within 2–24 hours of each other). Both SAMURAI and SPARTAN allowed enrollment of patients with CV risk factors (e.g., hypertension, hypercholesterolemia, smoking, obesity, diabetes), and SPARTAN also included patients with coronary artery disease (CAD), arrhythmia, and uncontrolled hypertension. In GLADIATOR, CV adverse event rates (incident and recurrent events, defined using relevant Standardized MedDRA Queries) were calculated for 3 time periods – treatment-emergent (<48 hours postdose), intermediate (48 hours–1 week postdose), and remote (>1 week postdose) – as it is possible some CV events were not reported as treatment emergent or were identified at a later date. Consequently, CV events occurring beyond 48 hours of dosing were also analyzed to determine whether such events increased in the treatment-emergent or intermediate periods compared with the remote period.
Results
At data cut-off for this interim analysis, 1978 patients had received ≥1 dose of lasmiditan (963 received 100 mg, 1015 received 200 mg) and 19,058 migraine attacks had been treated in GLADIATOR. Median duration in the study was 288 days. Eighty-one percent of patients had ≥1 CV risk factor, 0.3% had CAD, and 35.0% had low high-density lipoprotein cholesterol. No vasoconstriction-related CV events (e.g. angina) occurred in the treatment-emergent period, and such events were rarely observed in general (absolute number ranged from 1 to 3, all in remote period, limiting clinical interpretation). As expected, treatment-related CV events (palpitations and tachycardia) were more frequent in the treatment-emergent period than in the intermediate and remote periods.
Conclusions
In an interim analysis of the long-term GLADIATOR study, no vasoconstriction-related CV events occurred during the treatment-emergent period. The CV safety of lasmiditan was generally consistent with data from single-attack studies.