lasmiditan
{{Short description|Chemical compound}}
{{Use dmy dates|date=March 2024}}
{{Drugbox
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| verifiedrevid = 451563097
| image = Lasmiditan.svg
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| pronounce = {{IPAc-en|l|æ|z|ˈ|m|ɪ|d|ɪ|t|æ|n}}
{{respell|laz|MID|i|tan}}
| tradename = Reyvow, Rayvow
| Drugs.com = {{Drugs.com|monograph|lasmiditan-succinate}}
| MedlinePlus = a620015
| DailyMedID = Lasmiditan
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| routes_of_administration = By mouth, intravenous
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| ATC_prefix = N02
| ATC_suffix = CC08
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| legal_US = Schedule V
| legal_US_comment = {{cite web | title=2020 - Placement of Lasmiditan in Schedule V | website=DEA Diversion Control Division | date=31 January 2020 | url=https://www.deadiversion.usdoj.gov/fed_regs/rules/2020/fr0131.htm | access-date=31 January 2020 | archive-date=31 January 2020 | archive-url=https://web.archive.org/web/20200131195103/https://www.deadiversion.usdoj.gov/fed_regs/rules/2020/fr0131.htm | url-status=live }}
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| CAS_number = 439239-90-4
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| PubChem = 11610526
| IUPHAR_ligand = 3928
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB11732
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 9785281
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| UNII = 760I9WM792
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| KEGG = D10338
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| synonyms = COL-144
| IUPAC_name = 2,4,6-Trifluoro-N-[6-[(1-methyl-4-piperidinyl)carbonyl]-2-pyridinyl]benzamide
| C=19 | H=18 | F=3 | N=3 | O=2
| SMILES = CN1CCC(CC1)C(=O)C2=NC(=CC=C2)NC(=O)C3=C(C=C(C=C3F)F)F
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C19H18F3N3O2/c1-25-7-5-11(6-8-25)18(26)15-3-2-4-16(23-15)24-19(27)17-13(21)9-12(20)10-14(17)22/h2-4,9-11H,5-8H2,1H3,(H,23,24,27)
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| StdInChIKey = XEDHVZKDSYZQBF-UHFFFAOYSA-N
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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. It is not useful for prevention. It is taken by mouth.
Common side effects include sleepiness, dizziness, tiredness, and numbness.{{cite press release |title=FDA approves new treatment for patients with migraine |url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-patients-migraine |website=U.S. Food and Drug Administration (FDA) |access-date=17 October 2019 |date=11 October 2019 | archive-url=https://web.archive.org/web/20191116075147/https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-patients-migraine | archive-date=16 November 2019 | url-status=dead }} {{PD-notice}}{{cite web | title=Lasmiditan (Professional Patient Advice) | website=Drugs.com | date=4 June 2019 | url=https://www.drugs.com/ppa/lasmiditan.html | access-date=23 February 2020 | archive-date=27 January 2020 | archive-url=https://web.archive.org/web/20200127042427/https://www.drugs.com/ppa/lasmiditan.html | url-status=live }}
Lasmiditan was approved in the United States in October 2019 and became available in February 2020.{{cite press release | title=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 | website=Eli Lilly and Company | date=31 January 2020 | url=https://investor.lilly.com/news-releases/news-release-details/lillys-reyvowtm-lasmiditan-c-v-first-and-only-medicine-new-class | access-date=23 February 2020 | archive-date=23 February 2020 | archive-url=https://web.archive.org/web/20200223204341/https://investor.lilly.com/news-releases/news-release-details/lillys-reyvowtm-lasmiditan-c-v-first-and-only-medicine-new-class | url-status=live }} It was developed by Eli Lilly. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.{{cite web | title=New Drug Therapy Approvals 2019 | website=U.S. Food and Drug Administration | date=31 December 2019 | url=https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2019 | access-date=15 September 2020 | archive-date=16 September 2020 | archive-url=https://web.archive.org/web/20200916144738/https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2019 | url-status=dead }}
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,{{cite web|url=http://www.prous.com/molecules/default.asp?ID=198|archive-url=https://web.archive.org/web/20110728112115/http://www.prous.com/molecules/default.asp?ID=198|url-status=dead|archive-date=28 July 2011|publisher=Prous Science|title=Molecule of the Month July 2010: Lasmiditan hydrochloride|access-date=3 August 2011}} although a 1998 review has found such side-effects to rarely occur in people taking triptans.{{cite journal | vauthors = Dahlöf CG, Mathew N | title = Cardiovascular safety of 5HT1B/1D agonists--is there a cause for concern? | journal = Cephalalgia | volume = 18 | issue = 8 | pages = 539–545 | date = October 1998 | pmid = 9827245 | doi = 10.1046/j.1468-2982.1998.1808539.x | s2cid = 30125923 }}{{cite book| vauthors = Mutschler E, Geisslinger G, Kroemer HK, Schäfer-Korting M |title= Arzneimittelwirkungen |publisher= Wissenschaftliche Verlagsgesellschaft|location=Stuttgart|date=2001|edition=8th|page=265|isbn=978-3-8047-1763-3|oclc=47700647|language=German}}
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.{{cite web | title=Reyvow- lasmiditan tablet | website=DailyMed | date=11 October 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aea3358c-ff41-4490-9e6d-c7bf7b3de13f | access-date=15 November 2019 | archive-date=25 November 2020 | archive-url=https://web.archive.org/web/20201125230434/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aea3358c-ff41-4490-9e6d-c7bf7b3de13f | url-status=live }}
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.{{Cite web | url=http://www.fiercebiotech.com/biotech/lilly-buys-migraine-biotech-colucid-for-960m-and-drug-it-out-licensed | title=Lilly buys migraine biotech CoLucid, and the drug it outlicensed, for $960M | date=18 January 2017 | access-date=30 January 2017 | archive-date=25 September 2020 | archive-url=https://web.archive.org/web/20200925032246/https://www.fiercebiotech.com/biotech/lilly-buys-migraine-biotech-colucid-for-960m-and-drug-it-out-licensed | url-status=live }} The drug is protected by patents until 2031.{{Cite web | url=http://adisinsight.springer.com/drugs/800028519 | title=Lasmiditan - Eli Lilly and Company - AdisInsight | access-date=30 January 2017 | archive-date=26 September 2021 | archive-url=https://web.archive.org/web/20210926081044/https://adisinsight.springer.com/drugs/800028519 | url-status=live }}
Phase II clinical trials for dose finding purposes were completed in 2007, for an intravenous form{{cite journal | title=A Placebo-Controlled Adaptive Treatment Assignment Study of Intravenous COL-144 in the Acute Treatment of Migraine | website=ClinicalTrials.gov | date=8 November 2019 | url=https://clinicaltrials.gov/ct2/show/NCT00384774 | access-date=23 February 2020 | archive-date=23 February 2020 | archive-url=https://web.archive.org/web/20200223211109/https://clinicaltrials.gov/ct2/show/NCT00384774 | url-status=live }} and in early 2010, for an oral form.{{cite journal | title=Dose-ranging Study of Oral COL-144 in Acute Migraine Treatment | website=ClinicalTrials.gov | date=20 December 2019 | url=https://clinicaltrials.gov/ct2/show/NCT00883051 | access-date=23 February 2020 | archive-date=23 February 2020 | archive-url=https://web.archive.org/web/20200223211107/https://clinicaltrials.gov/ct2/show/NCT00883051 | url-status=live }} Eli Lilly submitted a new drug application to the U.S. Food and Drug Administration (FDA) in November 2018.{{Cite press release|title=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|url=http://www.prnewswire.com/news-releases/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-300750141.html|publisher=Eli Lilly and Company|via=PR Newswire|date=14 November 2018|access-date=12 October 2019|archive-date=12 October 2019|archive-url=https://web.archive.org/web/20191012233854/https://www.prnewswire.com/news-releases/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-300750141.html|url-status=live}}
Three phase III clinical trials were completed. The SPARTAN trial compared placebo with 50, 100, and 200 mg of lasmiditan.{{ClinicalTrialsGov|NCT02605174|Three Doses of Lasmiditan (50 mg, 100 mg and 200 mg) Compared to Placebo in the Acute Treatment of Migraine (SPARTAN)}} 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.{{ClinicalTrialsGov|NCT02565186|An Open-label, Long-term, Safety Study of Lasmiditan for the Acute Treatment of Migraine (GLADIATOR)}}
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.{{Cite web | url=https://investor.lilly.com/releasedetail.cfm?ReleaseID=1036101 | title=Lilly Announces Positive Results for Second Phase 3 Study of Lasmiditan for the Acute Treatment of Migraine | access-date=5 August 2017 | archive-url=https://web.archive.org/web/20170805220425/https://investor.lilly.com/releasedetail.cfm?ReleaseID=1036101 | archive-date=5 August 2017 | url-status=dead }}
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. Trials were conducted at 224 sites in the United States, the United Kingdom, and Germany.
The FDA approved the drug in October 2019.{{cite web | title=Drug Trials Snapshots: Reyvow | website=U.S. Food and Drug Administration (FDA) | date=11 October 2019 | url=http://www.fda.gov/drugs/drug-trials-snapshots-reyvow | access-date=26 January 2020 | archive-date=13 December 2019 | archive-url=https://web.archive.org/web/20191213231445/https://www.fda.gov/drugs/drug-trials-snapshots-reyvow | url-status=dead }} {{PD-notice}} It was placed into Schedule V in January 2020.{{cite web|title=Schedules of Controlled Substances: Placement of Lasmiditan in Schedule V|url=https://www.federalregister.gov/documents/2020/01/31/2020-01957/schedules-of-controlled-substances-placement-of-lasmiditan-in-schedule-v|date=31 January 2020|website=Federal Register|access-date=31 January 2020|archive-date=26 March 2021|archive-url=https://web.archive.org/web/20210326211708/https://www.federalregister.gov/documents/2020/01/31/2020-01957/schedules-of-controlled-substances-placement-of-lasmiditan-in-schedule-v|url-status=live}}
Society and culture
= Legal status =
On 23 June 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European 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. The applicant for this medicinal product is Eli Lilly Nederland B.V.{{cite web | title=Rayvow: Pending EC decision | website=European Medicines Agency (EMA) | date=23 June 2022 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/rayvow | access-date=26 June 2022 | archive-date=26 June 2022 | archive-url=https://web.archive.org/web/20220626014346/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/rayvow | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Rayvow was approved for medical use in the European Union in August 2022.{{cite web | title=Rayvow EPAR | website=European Medicines Agency (EMA) | date=14 September 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/rayvow | access-date=6 October 2022 | archive-date=6 October 2022 | archive-url=https://web.archive.org/web/20221006034723/https://www.ema.europa.eu/en/medicines/human/EPAR/rayvow | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.{{cite web | title=Rayvow Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1587.htm | access-date=3 March 2023}}
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 by Health 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.{{cite web|url=https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detailTwo.php?lang=en&linkID=RDS00789|title=Regulatory Decision Summary - Reyvow|date=23 October 2014 |publisher=Health Canada|access-date=22 June 2023}}
References
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{{Serotonin receptor modulators}}
{{Triptans}}
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