Lasmiditan: Difference between revisions

{{Short description|Chemical compound}}

{{Use dmy dates|date=March 2024}}

| Verifiedfields = changed

| verifiedrevid = 451563097

| image = Lasmiditan.svg

| width =

| alt =

| caption =

<!-- Clinical data -->

| pronounce = {{IPAc-en|l|æ|z|ˈ|m|ɪ|d|ɪ|t|æ|n}}<br />{{respell|laz|MID|i|tan}}

| tradename = Reyvow, Rayvow

| Drugs.com = {{Drugs.com|monograph|lasmiditan-succinate}}

| MedlinePlus = a620015

| DailyMedID = Lasmiditan

| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->

| pregnancy_AU_comment =

| pregnancy_category=

| routes_of_administration = [[Oral administration|By mouth]], [[intravenous]]

| class =

| ATC_prefix = N02

| ATC_suffix = CC08

| ATC_supplemental =

<!-- Legal status -->

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->

| legal_BR_comment =

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled-->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

| legal_UK_comment =

| legal_US = Schedule V

| legal_US_comment = <ref name="Reyvow FDA label" /><ref name="DEA">{{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 }}</ref>

| legal_EU = Rx-only

| legal_EU_comment = <ref name="Rayvow EPAR" />

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->

| legal_UN_comment =

| legal_status = <!--For countries not listed above-->

<!-- Pharmacokinetic data -->

| bioavailability =

| protein_bound =

| metabolism =

| metabolites =

| onset =

| elimination_half-life =

| duration_of_action =

| excretion =

<!-- Identifiers -->

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 439239-90-4

| CAS_supplemental =

| IUPHAR_ligand = 3928

| DrugBank = DB11732

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 9785281

| KEGG_Ref = {{keggcite|changed|kegg}}

| KEGG = D10338

| ChEBI_Ref =

| ChEBI =

| ChEMBL_Ref =

| ChEMBL =

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = COL-144

<!-- Chemical and physical data -->

| IUPAC_name = 2,4,6-Trifluoro-''N''-[6-[(1-methyl-4-piperidinyl)carbonyl]-2-pyridinyl]benzamide

| 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)

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = XEDHVZKDSYZQBF-UHFFFAOYSA-N

| density =

| density_notes =

| melting_point =

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

<!-- Definition and medical uses -->

'''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 (symptom)|aura]] (a sensory phenomenon or visual disturbance) in adults.<ref name="Reyvow FDA label" /> It is not useful for prevention.<ref name="Reyvow FDA label" /> It is taken [[Oral administration|by mouth]].<ref name="Reyvow FDA label" />

<!-- Side effects and mechanism -->

Common side effects include sleepiness, dizziness, tiredness, and numbness.<ref name="FDA2019">{{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=live }} {{PD-notice}}</ref><ref>{{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 }}</ref>

<!-- History and culture -->

Lasmiditan was approved in the United States in October 2019<ref name="FDA2019"/> and became available in February 2020.<ref>{{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 }}</ref> It was developed by [[Eli Lilly]].<ref name="FDA2019"/> The U.S. [[Food and Drug Administration]] (FDA) considers it to be a [[first-in-class medication]].<ref>{{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=live }}</ref>

==Pharmacology==

===Mechanism of action===

Lasmiditan is a [[serotonin receptor agonist]] that, like the unsuccessful [[LY-334,370]], selectively binds to the [[5-HT1F receptor|5-HT_1F receptor]] subtype. A number of [[triptan]]s have been shown to act on this subtype as well, but only after their affinity for [[5-HT1B receptor|5-HT_1B]] and [[5-HT1D receptor|5-HT_1D]] 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]],<ref name="Prous">{{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}}</ref> although a 1998 review has found such side-effects to rarely occur in people taking triptans.<ref>{{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 }}</ref><ref name="Mutschler">{{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}}</ref>

==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 (drug)|alcohol]] or other CNS depressants.<ref name="Reyvow FDA label">{{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 }}</ref>

== 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.<ref>{{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 }}</ref> The drug is protected by patents until 2031.<ref name="adisinsight">{{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 }}</ref>

Phase II clinical trials for dose finding purposes were completed in 2007, for an intravenous form<ref name="NCT00384774">{{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 }}</ref> and in early 2010, for an oral form.<ref name="NCT00883051">{{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 }}</ref> Eli Lilly submitted a [[new drug application]] to the U.S. [[Food and Drug Administration]] (FDA) in November 2018.<ref name="lillyNDA2018">{{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}}</ref>

Three phase III clinical trials were completed. The SPARTAN trial compared placebo with 50, 100, and 200&nbsp;mg of lasmiditan.<ref>{{ClinicalTrialsGov|NCT02605174|Three Doses of Lasmiditan (50 mg, 100 mg and 200 mg) Compared to Placebo in the Acute Treatment of Migraine (SPARTAN)}}</ref> SAMURAI compared placebo with 100 and 200&nbsp;mg doses of lasmiditan. GLADIATOR is an [[open-label]] study that compared 100 and 200&nbsp;mg doses of lasmiditan in subjects that received the drug as part of a prior trial.<ref>{{ClinicalTrialsGov|NCT02565186|An Open-label, Long-term, Safety Study of Lasmiditan for the Acute Treatment of Migraine (GLADIATOR)}}</ref>

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.<ref>{{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 }}</ref>

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.<ref name="FDA Snapshot" /> Trials were conducted at 224 sites in the United States, the United Kingdom, and Germany.<ref name="FDA Snapshot" />

The FDA approved the drug in October 2019.<ref name="FDA Snapshot">{{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=live }} {{PD-notice}}</ref> It was placed into [[Controlled Substances Act#Schedule V drugs|Schedule V]] in January 2020.<ref name="DEA" /><ref>{{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}}</ref>

== 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.<ref name="Rayvow: Pending EC decision" /> The applicant for this medicinal product is Eli Lilly Nederland B.V.<ref name="Rayvow: Pending EC decision">{{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.</ref> Rayvow was approved for medical use in the European Union in August 2022.<ref name="Rayvow EPAR">{{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.</ref><ref>{{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}}</ref>

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.<ref name=hc2021>{{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}}</ref>

== References ==

{{reflist}}

{{Serotonin receptor modulators}}

{{Triptans}}

{{Portal bar | Medicine}}

[[Category:5-HT1F agonists]]

[[Category:Drugs developed by Eli Lilly and Company]]

[[Category:Fluoroarenes]]

[[Category:Piperidines]]

[[Category:Pyridines]]