Lasmiditan

Lasmiditan, sold under the brand name Reyvow, is a medication used for the acute (active but short-term) treatment of migraine with or without aura (a sensory phenomenon or visual disturbance) in adults.[2] It is not useful for prevention.[2] It is taken by mouth.[2]

Lasmiditan
Clinical data
Trade namesReyvow
Other namesCOL-144
AHFS/Drugs.comMonograph
MedlinePlusa620015
License data
Routes of
administration		By mouth, intravenous
ATC code
  • none
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC19H18F3N3O2
Molar mass377.367 g·mol−1
3D model (JSmol)
 NY (what is this?)  (verify)

Common side effects include sleepiness, dizziness, tiredness, and numbness.[3][4]

Lasmiditan was approved in the United States in October 2019[3] and became available in February 2020.[5] It was developed by Eli Lilly.[3] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[6]

Pharmacology

Mechanism of action

Lasmiditan is a serotonin receptor agonist that, like the unsuccessful LY-334,370, selectively binds to the 5-HT1F receptor subtype. A number of triptans have been shown to act on this subtype as well, but only after their affinity for 5-HT1B and 5-HT1D has been made responsible for their anti-migraine activity. The lack of affinity for these receptors might result in fewer side effects related to vasoconstriction compared to triptans in susceptible people, such as those with ischemic heart disease, Raynaud's phenomenon or after a myocardial infarction,[7] although a 1998 review has found such side-effects to rarely occur in people taking triptans.[8][9]

Adverse effects

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 with alcohol or other CNS depressants.[2]

History

Lasmiditan was discovered by Eli 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.[10] The drug is protected by patents until 2031.[11]

Phase II clinical trials for dose finding purposes were completed in 2007, for an intravenous form[12] and in early 2010, for an oral form.[13] Eli Lilly submitted a new drug application to the U.S. Food and Drug Administration (FDA) in November 2018.[14]

Three Phase III clinical trials were completed. The SPARTAN trial compared placebo with 50, 100, and 200 mg of lasmiditan.[15] SAMURAI compared placebo with 100 and 200 mg doses of lasmiditan. GLADIATOR is an open-label study that compared 100 and 200 mg doses of lasmiditan in subjects that received the drug as part of a prior trial.[16]

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.[17]

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.[18] Trials were conducted at 224 sites in the United States, the United Kingdom, and Germany.[18]

The FDA approved the drug in October 2019.[18] However, as of October 2019, the drug was awaiting Drug Enforcement Administration (DEA) scheduling before it was made available in the United States.[19] It was placed into Schedule V in January 2020.[20][1]

Dosage

Lasmiditan is delivered in 50 & 100 mg tablet form.[21]

References
  1. "2020 - Placement of Lasmiditan in Schedule V". DEA Diversion Control Division. 31 January 2020. Retrieved 31 January 2020.
  2. "Reyvow- lasmiditan tablet". DailyMed. 11 October 2019. Retrieved 15 November 2019.
  3. "FDA approves new treatment for patients with migraine". U.S. Food and Drug Administration (FDA) (Press release). 11 October 2019. Archived from the original on 16 November 2019. Retrieved 17 October 2019. This article incorporates text from this source, which is in the public domain.
  4. "Lasmiditan (Professional Patient Advice)". Drugs.com. 4 June 2019. Retrieved 23 February 2020.
  5. "Lilly's Reyvow (lasmiditan) C-V, the First and Only Medicine in a New Class of Acute Treatment for Migraine (ditan), Now Available for Prescription". Eli Lilly and Company. 31 January 2020. Retrieved 23 February 2020.
  6. "New Drug Therapy Approvals 2019". U.S. Food and Drug Administration. 31 December 2019. Retrieved 15 September 2020.
  7. "Molecule of the Month July 2010: Lasmiditan hydrochloride". Prous Science. Archived from the original on 28 July 2011. Retrieved 3 August 2011.
  8. Dahlöf CG, Mathew N (October 1998). "Cardiovascular safety of 5HT1B/1D agonists--is there a cause for concern?". Cephalalgia. 18 (8): 539–45. doi:10.1046/j.1468-2982.1998.1808539.x. PMID 9827245. S2CID 30125923.
  9. Mutschler E, Geisslinger G, Kroemer HK, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 265. ISBN 978-3-8047-1763-3. OCLC 47700647.
  10. "Lilly buys migraine biotech CoLucid, and the drug it outlicensed, for $960M".
  11. "Lasmiditan - Eli Lilly and Company - AdisInsight".
  12. "A Placebo-Controlled Adaptive Treatment Assignment Study of Intravenous COL-144 in the Acute Treatment of Migraine". ClinicalTrials.gov. Retrieved 23 February 2020.
  13. "Dose-ranging Study of Oral COL-144 in Acute Migraine Treatment". ClinicalTrials.gov. Retrieved 23 February 2020.
  14. "Lilly Submits New Drug Application to the FDA for Lasmiditan for Acute Treatment of Migraine, Receives Breakthrough Therapy Designation for Emgality (galcanezumab-gnlm) for Prevention of Episodic Cluster Headache". Eli Lilly and Company. 14 November 2018. Retrieved 12 October 2019 – via PR Newswire.
  15. Clinical trial number NCT02605174 for "Three Doses of Lasmiditan (50 mg, 100 mg and 200 mg) Compared to Placebo in the Acute Treatment of Migraine (SPARTAN)" at ClinicalTrials.gov
  16. Clinical trial number NCT02565186 for "An Open-label, Long-term, Safety Study of Lasmiditan for the Acute Treatment of Migraine (GLADIATOR)" at ClinicalTrials.gov
  17. "Lilly Announces Positive Results for Second Phase 3 Study of Lasmiditan for the Acute Treatment of Migraine". Archived from the original on 5 August 2017. Retrieved 5 August 2017.
  18. "Drug Trials Snapshots: Reyvow". U.S. Food and Drug Administration (FDA). 11 October 2019. Retrieved 26 January 2020.
  19. Vinluan F (11 October 2019). "FDA OKs Lilly's Lasmiditan, First New Acute Migraine Drug in Decades". Xconomy. Retrieved 12 October 2019.
  20. "Schedules of Controlled Substances: Placement of Lasmiditan in Schedule V". Federal Register. 31 January 2020.
  21. "Reyvow (Lasmiditan Tablets): Uses, Dosage, Side Effects, Interactions, Warning". RxList. Retrieved 20 August 2020.
  • "Lasmiditan". Drug Information Portal. U.S. National Library of Medicine.
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