DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20190163

Lasmiditan: new drug for acute migraine

Dick Brashier, Sachin Maggo, Shaman Gill, Piyush Angrish, Anuj Singh, Deepmala Rawat

Abstract


Migraine is ranked by the World Health Organization as the world’s second leading cause of disability. The current state of knowledge suggests that migraine is a neuronal process involving activation and sensitization of the trigeminal nociceptors and the trigeminocervical complex, as well as cortical spreading depression and abnormal brainstem activity. The present non vascular etiological basis has opened a new horizon in the treatment of acute migraine targeting the trigeminal pathways. Lasmiditan, a highly selective 5-HT1F receptor agonist, acts on the trigeminal system without causing vasoconstriction because of its low affinity for 5-HT1B receptors. The compound belongs to a new class of drugs “ditans” and its mechanism of action is neuronal without evidence of vasoactive effects as seen with triptans. It lowers plasma protein extravasation decreasing the neurogenic inflammation of the dura and suppress neuronal firing within the trigeminal nucleus caudalis. Also, 5HT1F agonists have shown to decrease c-fos activity within trigeminal nucleus thereby reducing the level of synaptic activation. The onset of action of lasmiditan is fast, shows rapid absorption, oral bioavailability of 40% and linear pharmacokinetics. Most common adverse reactions seen are dizziness, paresthesia, somnolence, nausea, fatigue and lethargy with dizziness being the most recurrently reported adverse event. Clinical trials for lasmiditan to date have been positive, and maiden results suggest that lasmiditan may be a new safe and effective option for acute migraine treatment, especially for patients refractory to or unable to tolerate triptans, and/or for patients with pre-existing cardiovascular disease. With Eli Lilly and Co. having already applied for US FDA approval in Nov 2018, lasmiditan may soon be a new addition to the mounting armoury of drugs against migraine.


Keywords


Lasmiditan, Migraine, 5 HT1F receptors

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References


GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1211-59.

Schulte LH, May A. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain. 2016;139(Pt 7):1987-93.

May A, Schulte LH. Chronic migraine: risk factors, mechanisms and treatment. Nat Rev Neurol. 2016;12(8):455-64.

Humphrey PP, Feniuk W, Perren MJ, Beresford IJ, Skingle M, Whalley ET. Serotonin and migraine. Ann N Y Acad Sci. 1990;600(600):587-600.

Pietrobon D, Moskowitz MA. Pathophysiology of migraine. Annu Rev Physiol. 2013;75:365-91.

Visser WH, Jaspers NM, de Vriend RH, Ferrari MD. Chest symptoms after sumatriptan: a two-year clinical practice review in 735 consecutive migraine patients. Cephalalgia. 1996;16(8):554-9.

Dodick D, Lipton RB, Martin V, Papademetriou V, Rosamond W, MaassenVanDenBrink A, et al. Consensus statement: Cardiovascular safety profile of triptans (5‐HT1B/1D agonists) in the acute treatment of migraine. Headache. J Head Face Pain. 2004 May;44(5):414-25.

O’Connor P, Gladstone P. Oral sumatriptan-associated transmural myocardial infarction. Neurology. 1995;45(12):2274-6.

Jayamaha JE, Street MK. Fatal cerebellar infarction in a migraine sufferer whilst receiving sumatriptan. Intensive Care Med. 1995;21(1):82-3.

Abbrescia VD, Pearlstein L, Kotler M. Sumatriptan-associated myocardial infarction: report of case with attention to potential risk factors. The Journal of the American Osteopathic Association. 1997 Mar;97(3):162-4.

Bally M, Dendukuri N, Rich B, Nadeau L, Helin-Salmivaara A, Garbe E, et al. Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data. BMJ. 2017 May 9;357:j1909.

Viana M, Genazzani AA, Terrazzino S, Nappi G, Goadsby PJ. Triptannonresponders: do they exist and who are they? Cephalalgia 2013;33:891-6.

Nelson DL, Phebus LA, Johnson KW, Wainscott DB, Cohen ML, Calligaro DO, et al. Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan. Cephalalgia. 2010 Oct;30(10):1159-69.

Kuca B, Silberstein SD, Wietecha L, Berg PH, Dozier G, Lipton RB, et al. Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study. Neurology. 2018 Dec 11;91(24):e2222-32.

US Department of Health and Human Services, Food and Drug Administration. Special Protocol Assessment (SPA) guidance for industry: OMB control number 0910-0470. Available at: fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm498793.pdf. Accessed November 6, 2018.

Kuca B, Silberstein SD, Wietecha L, Berg PH, Dozier G, Lipton RB, et al. Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study. Neurology. 2018 Nov 16:10-212.

Nelson DL, Phebus LA, Johnson KW, Wainscott DB, Cohen ML, Calligaro DO, et al. Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan. Cephalalgia. 2010 Oct;30(10):1159-69.

Goadsby PJ, Classey JD. Evidence for serotonin (5-HT)1B, 5-HT1D and 5-HT1F receptor inhibitory effects on trigeminal neurons with craniovascular input. Neuroscience. 2003;122(2):491-8.

Cohen ML, Schenck K. 5-Hydroxytryptamine1F receptors do not participate in vasoconstriction: lack of vasoconstriction to LY344864, a selective serotonin1F receptor agonist in rabbit saphenous vein. J Pharmacol Expe Therapeu. 1999 Sep 1;290(3):935-9.

Johnson KW, Schaus JM, Durkin MM, Audia JE, Kaldor SW, Flaugh ME, et al. 5-HT1F receptor agonists inhibit neurogenic dural inflammation in guinea pigs. Neuroreport. 1997 Jul 7;8(9):2237-9.

Charles A. Advances in the basic and clinical science of migraine. Ann Neurol. 2009;65(5):491-8.

Goadsby PJ, Lipton RB, Ferrari MD. Migraine--current understanding and treatment. N Engl J Med. 2002;346(4):257-70.

Shepheard S, Edvinsson L, Cumberbatch M, Williamson D, Mason G, Webb J, et al. Possible antimigraine mechanisms of action of the 5HT1F receptor agonist LY334370. Cephalalgia. 1999 Dec;19(10):851-8.

Negro A, Koverech A, Martelletti P. Serotonin receptor agonists in the acute treatment of migraine: a review on their therapeutic potential. J Pain Res. 2018;11:515-26.

Färkkilä M, Diener HC, Géraud G, Láinez M, Schoenen J, Harner N, et al. Efficacy and tolerability of lasmiditan, an oral 5-HT1F receptor agonist, for the acute treatment of migraine: a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study. Lancet Neurol. 2012 May 1;11(5):405-13.

Pilgrim AJ, Dussault B, Rupniak NM, White J, Mazur D, DiSanto AR. col-144, an orally bioavailable selective 5-ht1f receptor agonist for acute migraine therapy: Po34. Cephalalgia. 2009 Oct 1;29:24-5.

SAMURAI: Lasmiditan Reduces Pain in Acute Migraine; 2018. Available ar: https://globenewswire.com/news-release/2016/09/06/869611/0/en/ CoLucid-Pharmaceuticals-Announces-Achievement-of-Both-Primaryand-Key-Secondary-Endpoints-in-the-SAMURAI-Phase-3-PivotalTrial-of-Lasmiditan-in-Migraine.html. Accessed March 19, 2018.

Lilly Announces Positive Results for Second Phase 3 Study of Lasmiditan for the Acute Treatment of Migraine (NYSE:LLY); 2018. Available at: https://investor.lilly.com/static-files/15cf1efc-da8f-485c-90016ff3b432b129. Accessed March 19, 2018.

CoLucid Pharmaceuticals Provides Interim Update on GLADIATOR [webpage on the Internet]. GlobeNewswire, Inc.; 2016. Available at: https://globenewswire.com/news-release/2016/09/19/872772/0/en/ CoLucid-Pharmaceuticals-Provides-Interim-Update-on-GLADIATOR. html. Accessed August 10, 2018.