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Lasmiditan

Lasmiditan
Lasmiditan skeletal.svg
Clinical data
Trade namesReyvow
SynonymsCOL-144
AHFS/Drugs.comreyvow
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 mass377.36 g/mol g·mol−1
3D model (JSmol)
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Lasmiditan, sold under the trade name Reyvow, is a medication used for the acute treatment of migraine headaches.[1] It is not useful for prevention.[1] It is taken by mouth.[1]

Common side effects include sleepiness, dizziness, tiredness, and numbness.[1] It is a "neurally acting anti-migraine agent" ditan.

Lasmiditan was approved in the United States in 2019.[1] It was developed by Eli Lilly.[1] As of October 2019 the medication is not avaliable and the proposed price is unclear.[2]

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 patients, such as those with ischemic heart disease, Raynaud's phenomenon or after a myocardial infarction,[3] although a 1998 review has found such side-effects to rarely occur in patients taking triptans.[4][5]

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.[6] The drug is protected by patents until 2031.[7]

Phase II clinical trials for dose finding purposes were completed in 2007 for an intravenous form[8] and in early 2010 for an oral form.[9] Eli Lilly submitted a new drug application to the FDA in November 2018.[10]

Three phase III clinical trials were completed. The SPARTAN trial compared placebo with 50, 100, and 200 mg of lasmiditan.[11] 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 patients that received the drug as part of a prior trial.[12]

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 patients were free of their most bothersome symptom (MBS) compared with placebo at two hours following the first dose.[13]

The FDA approved the drug on 11 October 2019. However, the drug is awaiting Drug Enforcement Administration (DEA) scheduling before it is made available in the United States.[14]

References

  1. ^ a b c d e f Commissioner, Office of the (11 October 2019). "FDA approves new treatment for patients with migraine". FDA. Retrieved 17 October 2019.
  2. ^ "Lilly's 1-drug migraine business gets support with new approval". BioPharma Dive. Retrieved 17 October 2019.
  3. ^ "Molecule of the Month July 2010: Lasmiditan hydrochloride". Prous Science. Retrieved 2011-08-03.
  4. ^ Dahlöf, CG; Mathew, N (1998). "Cardiovascular safety of 5HT1B/1D agonists--is there a cause for concern?". Cephalalgia: An International Journal of Headache. 18 (8): 539–45. doi:10.1046/j.1468-2982.1998.1808539.x. PMID 9827245.
  5. ^ Mutschler, Ernst; Geisslinger, Gerd; Kroemer, Heyo K.; Schäfer-Korting, Monika (2001). Arzneimittelwirkungen (in German) (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 265. ISBN 978-3-8047-1763-3. OCLC 47700647.
  6. ^ [www.fiercebiotech.com]
  7. ^ [adisinsight.springer.com]
  8. ^ Clinical trial number NCT00384774 for "A Placebo-Controlled Adaptive Treatment Assignment Study of Intravenous COL-144 in the Acute Treatment of Migraine" at ClinicalTrials.gov
  9. ^ Clinical trial number NCT00883051 for "Dose-ranging Study of Oral COL-144 in Acute Migraine Treatment" at ClinicalTrials.gov
  10. ^ "Lilly Submits New Drug Application to the FDA for Lasmiditan". PR Newswire. 14 November 2018. Retrieved 12 October 2019.
  11. ^ 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
  12. ^ Clinical trial number NCT02565186 for "An Open-label, Long-term, Safety Study of Lasmiditan for the Acute Treatment of Migraine (GLADIATOR)" at ClinicalTrials.gov
  13. ^ [investor.lilly.com]
  14. ^ Frank Vinluan (11 October 2019). "FDA OKs Lilly's Lasmiditan, First New Acute Migraine Drug in Decades". Xconomy. Retrieved 12 October 2019.