Lasmiditan is used for the acute (active but short-term) treatment ofmigraine with or withoutaura (a sensory phenomenon or visual disturbance) in adults.[1] It is not indicated for migraineprevention.[1]
There is a risk of driving impairment while taking lasmiditan. People are advised not to drive or operate machinery for at least eight hours after taking lasmiditan, even if they feel well enough to do so. People who cannot follow this advice are advised not to take lasmiditan. The drug causes central nervous system (CNS) depression, including dizziness and sedation. It should be used with caution if taken in combination withalcohol or other CNS depressants.[1]
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified.Refs:[9][10][11][12]
Lasmiditan is aserotonin receptor agonist that, like the unsuccessfulLY-334,370, selectively binds to the5-HT1F receptor subtype. A number oftriptans have been shown to act on this subtype as well, but only after their affinity for5-HT1B and5-HT1D has been made responsible for their anti-migraine activity. The lack of affinity for these receptors might result in fewer side effects related tovasoconstriction compared to triptans in susceptible people, such as those withischemic heart disease,Raynaud's phenomenon or after amyocardial infarction,[13] although a 1998 review has found such side-effects to rarely occur in people taking triptans.[14][15] The broad receptor interactions of lasmiditan have been studied.[12][11]
Lasmiditan was discovered byEli Lilly and Company and was then relicensed to CoLucid Pharmaceuticals in 2006, until CoLucid was bought by Eli Lilly in 2017, to allow Eli Lilly to reacquire the drug's intellectual property.[16] The drug is protected by patents until 2031.[17]
Phase II clinical trials for dose finding purposes were completed in 2007, for an intravenous form[18] and in early 2010, for an oral form.[19] Eli Lilly submitted anew drug application to the U.S.Food and Drug Administration (FDA) in November 2018.[20]
Three phase III clinical trials were completed. The SPARTAN trial compared placebo with 50, 100, and 200 mg of lasmiditan.[21] SAMURAI compared placebo with 100 and 200 mg doses of lasmiditan. GLADIATOR is anopen-label study that compared 100 and 200 mg doses of lasmiditan in subjects that received the drug as part of a prior trial.[22]
Topline results from the SPARTAN trial showed that the drug induced met its primary and secondary endpoints in the trial. The primary result showed a statistically significant improvement in pain relief relative to placebo 2 hours after the first dose. The secondary result showed a statistically significantly greater percentage of subjects were free of their most bothersome symptom (MBS) compared with placebo at two hours following the first dose.[23]
The FDA approved lasmiditan primarily based on data from two clinical trials, Trial 1 (# NCT02439320) and Trial 2 (#NCT02605174) of 4439 subjects with migraine headaches with or without aura.[24] Trials were conducted at 224 sites in the United States, the United Kingdom, and Germany.[24]
The FDA approved the drug in October 2019.[24] It was placed intoSchedule V in January 2020.[2][8]
On 23 June 2022, theCommittee for Medicinal Products for Human Use (CHMP) of theEuropean Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Rayvow, intended for the treatment of migraine.[25] The applicant for this medicinal product is Eli Lilly Nederland B.V.[25] Rayvow was approved for medical use in the European Union in August 2022.[3][26]
Lasmiditan has not been approved for use in Canada. The drug sponsor in Canada, Eli Lilly Canada Inc., filed a New Drug Submission in February 2020 but cancelled the submission before a final decision was issued byHealth Canada. Health Canada had completed their review of the submission and did not find any deficiencies in the data packages provided in the submission. However, Health Canada and Eli Lilly could not come to agreement on the interpretation of the cardiovascular data and how it would be worded in the product monograph. The drug sponsor cancelled their submission on 26 January 2021 before Health Canada issued a final decision.[27]
^ab"Rayvow EPAR".European Medicines Agency (EMA). 14 September 2021.Archived from the original on 6 October 2022. Retrieved6 October 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^abRubio-Beltrán E, Labastida-Ramírez A, Haanes KA, van den Bogaerdt A, Bogers AJ, Zanelli E, Meeus L, Danser AH, Gralinski MR, Senese PB, Johnson KW, Kovalchin J, Villalón CM, MaassenVanDenBrink A (December 2019)."Characterization of binding, functional activity, and contractile responses of the selective 5-HT1F receptor agonist lasmiditan".British Journal of Pharmacology.176 (24):4681–4695.doi:10.1111/bph.14832.PMC6965684.PMID31418454.TABLE 1 Summary of pIC50 (negative logarithm of the molar concentration of these compounds at which 50% of the radioligand is displaced) and pKi (negative logarithm of the molar concentration of the Ki ) values of individual antimigraine drugs at 5‐HT receptors [...] TABLE 2 Summary of pEC50 values of cAMP (5‐HT1A/B/E/F and 5‐HT7), GTPγS (5‐HT1A/B/D/E/F), and IP (5‐HT2) assays of individual antimigraine drugs at 5‐HT receptors [...]
^Mutschler E, Geisslinger G, Kroemer HK, Schäfer-Korting M (2001).Arzneimittelwirkungen (in German) (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 265.ISBN978-3-8047-1763-3.OCLC47700647.
^Clinical trial numberNCT02605174 for "Three Doses of Lasmiditan (50 mg, 100 mg and 200 mg) Compared to Placebo in the Acute Treatment of Migraine (SPARTAN)" atClinicalTrials.gov
^Clinical trial numberNCT02565186 for "An Open-label, Long-term, Safety Study of Lasmiditan for the Acute Treatment of Migraine (GLADIATOR)" atClinicalTrials.gov
^ab"Rayvow: Pending EC decision".European Medicines Agency (EMA). 23 June 2022.Archived from the original on 26 June 2022. Retrieved26 June 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
This article incorporates text from this source, which is in thepublic domain.
