A DIFFERENT KIND OF MIGRAINE TREATMENT

REYVOW (lasmiditan) is the first and only FDA-approved ditan—a high-affinity 5-HT_1F receptor agonist¹

REYVOW presumably exerts its therapeutic effects by activating the 5-HT_1F receptor; however, the exact mechanism of action is unknown.¹

5-HT_1F receptors, involved in modulating pain signaling, are present on both the peripheral and central pain pathways.^2,3 Based on the location of 5-HT_1F receptors, REYVOW is believed to act both centrally and peripherally.³

In preclinical studies:

Though not demonstrated in humans, REYVOW was shown to cross the blood-brain barrier in an animal model⁴
REYVOW was shown to be lipophilic based on an in vitro assay⁴

REYVOW is a Selective 5-HT_1F Receptor Agonist¹

REYVOW is not a triptan. In preclinical studies, REYVOW was shown to have more than 440-fold greater selectivity for the 5-HT_1F receptor than for the 5-HT_1B and the 5-HT_1D receptors.^1,4

Activation of 5-HT_1F receptors has been observed in preclinical studies to:^2,5,6

Inhibit pain pathways, including the trigeminal nerve

Inhibit the release of neurotransmitters and neuropeptides

Not cause vasoconstriction of blood vessels

SELECT IMPORTANT SAFETY INFORMATION

Medication Overuse Headache
Overuse of acute migraine drugs may lead to exacerbation of headache (i.e., medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients including withdrawal of the overused drugs and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.

Discover how the REYVOW MOA is different

Video title animates on screen.
On-Screen Text: Mechanism of Action of REYVOW^™ (lasmiditan) (C-V) Tablets
Voiceover: Mechanism of action of REYVOW (lasmiditan) controlled substance schedule 5 tablets

Chapter title animates on-screen.
On-Screen Text: CHAPTER 1 Migraine and Serotonin (5-HT) _1F Receptors
Voiceover: Chapter 1 – Migraine and Serotonin (5-HT) _1F Receptors

We see a woman in pain. The brain is beginning to fade in. The camera will pan around to show a side view.
Voiceover: Migraine is a debilitating neurological disease.^1-4

We show the woman and her brain and nervous system anatomy. As we talk about the path of pain, the anatomy will be highlighted.
On-Screen Text: Trigeminovascular pain pathway Labels: Meninges, Trigeminal ganglion, Trigeminal nerve, Thalamus, Brain stem nuclei, eg, trigeminal nucleus caudalis
Voiceover: Migraine involves the trigeminovascular pain pathway, which consists of peripheral nerve endings that send signals from the meninges covering the brain to the trigeminal ganglion; the signal then continues on to the central nervous system brain stem nuclei.^1,5,6

We see a neuron signaling above a blood vessel, which is pulsing to indicate inflammation.
On-Screen Text: Neurogenic inflammation Labels: Neuron, 5-HT_1F receptor, Blood vessel
Voiceover: Nerve activity leading to the release of neuropeptides and neurotransmitters is thought to exacerbate neurogenic inflammation and nociceptor pain signaling in migraine.^1,5,7

In the neuronal environment we see synapses and neuropeptide release. We see nerve endings with 5-HT_1F receptors. There is a lot of signaling activity in the background.
On-Screen Text: Nociceptor pain signaling Labels: Neuron, 5-HT_1F receptor, Neurotransmitters
Voiceover: Serotonin (5-HT) _1F receptors may play a role in migraine.^5,8 5-HT_1F receptors are involved in modulating pain signaling and are present on both peripheral and central pain pathways.^7,9

We see the woman’s anatomy. The 5-HT_1F receptor lights up when activated and stops the pulse from going further down the nerve. Also the background signaling is reduced when agonist binds to the 5-HT_1F receptor.
On-Screen Text:

Inhibiting neurotransmitter and neuropeptide release
Thereby inhibiting their local activity and downstream neuronal signaling

Labels: Serotonin, 5-HT_1F receptor
Voiceover: Preclinical studies have shown that activation of 5-HT_1F receptors inhibits the release of neurotransmitters and neuropeptides, inhibits pain pathways, including the trigeminal nerve, and does not cause vasoconstriction of blood vessels.^5,7,10

The REYVOW logo animates on-screen, followed by the rest of the on-screen text.
On-Screen Text: INDICATION: REYVOW is indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use: REYVOW is not indicated for the preventive treatment of migraine. REYVOW may cause significant driving impairment. Please see Important Safety Information for REYVOW and links to Prescribing Information and Medication Guide below.
Voiceover: INDICATION: REYVOW is indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use: REYVOW is not indicated for the preventive treatment of migraine.

Chapter title animates on-screen.
On-Screen Text: Chapter 2 REYVOW (lasmiditan) is a high-affinity serotonin (5-HT) _1F receptor agonist. The first and only FDA-approved ditan.
Voiceover: Chapter 2 – REYVOW (lasmiditan) is a high-affinity serotonin (5-HT) _1F receptor agonist. The first and only FDA-approved ditan.¹¹

We see a hero shot of REYVOW flying in.
On-Screen Text: REYVOW is the first and only FDA-approved high-affinity serotonin (5-HT) _1F receptor agonist. Labels: REYVOW, 5-HT_1F receptor
Voiceover: REYVOW is the first and only FDA-approved high-affinity serotonin (5-HT) _1F receptor agonist.¹¹

We see REYVOW binding to the 5-HT_1F receptor. The receptor lights up when bound.
Labels: REYVOW, Neuron, 5-HT_1F receptor
Voiceover: REYVOW presumably exerts its therapeutic effects in the treatment of migraine through agonist effects at the 5-HT_1F receptor; however, the precise mechanism is unknown.¹¹

We see a blood vessel with REYVOW molecules crossing the blood-brain barrier to enter the central nervous system.
On-Screen Text: IN PRECLINICAL STUDIES:

Although not demonstrated in human, REYVOW was shown to cross the blood-brain barrier in animal models
REYVOW was shown to be lipophilic based on in vitro assays

Based on the location of the 5-HT_1F receptors, REYVOW is believed to act both centrally and peripherally.

Labels: REYVOW
Voiceover: Although not demonstrated in human, REYVOW was shown to cross the blood-brain barrier in animal models.¹² REYVOW was shown to be lipophilic based on in vitro assays.¹² Based on the location of the 5-HT_1F receptors, REYVOW is believed to act both centrally and peripherally.⁹

The background signaling is reduced when REYVOW binds to the 5-HT_1F receptor. The 5-HT_1F receptor lights up when activated and stops the pulse from going further down the nerve.
Labels: REYVOW, 5-HT_1F receptor, Neuron
Voiceover: REYVOW (lasmiditan) is a high-affinity serotonin (5-HT) _1F receptor agonist. It is the first and only FDA-approved ditan.¹¹

We see the woman again.
On-Screen Text: REYVOW (lasmiditan) is a high-affinity serotonin (5-HT) _1F receptor agonist. The first and only FDA-approved ditan.
Voiceover: REYVOW is indicated for the acute treatment of migraine with or without aura in adults.¹¹

References on-screen.
On-Screen Text:

References

Pietrobon D, Moskowitz MA. Pathophysiology of migraine. Annu Rev Physiol. 2013;75:365-391.
Viana M, Sances G, Ghiotto N, et al. Variability of the characteristics of a migraine attack within patients. Cephalalgia. 2016;36(9);825-830.
Monteith TS, Goadsby PJ. Acute migraine therapy: new drugs and new approaches. Curr Treat Options Neurol. 2011;13(1):1-14.
Sutherland HG, Griffiths LR. Genetics of migraine: insights into the molecular basis of migraine disorders. Headache. 2017;57:537-569.
Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffman J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97:553-622.
Russo AF. Calcitonin gene-related peptide (CGRP): a new target for migraine. Annu Rev Pharmacol Toxixol. 2015;55:533-552.
Rubio-Beltrán E, Labastida-Ramirez A, Villalón CM, MaassenVanDenBrink A. Is selective 5-HT_1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018;186:88-97.
Ramadan N, Skljarevski V, Phebus L, Johnson K. 5-HT_1F receptor agonists in acute migraine treatment: a hypothesis. Cephalalgia. 2003;23:776-785.
Vila-Pueyo M. Targeted 5-HT_1F therapies for migraine. Neurotherapeutics. 2018;15:291-303.
Ahn SK, Khalmuratova R, Jeon SY, et al. Colocalization of 5-HT_1F receptor and calcitonin gene-related peptide in rat vestibular nuclei. Neurosci Lett. 2009;465:151-156.
REYVOW [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC.
Data on file. Indianapolis, IN: Lilly USA, LLC. DOF-LM-US-0019.

The REYVOW logo animates on-screen, followed by the rest of the on-screen text.
On-Screen Text: INDICATION: REYVOW is indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use: REYVOW is not indicated for the preventive treatment of migraine. REYVOW may cause significant driving impairment. Please see Important Safety Information for REYVOW and links to Prescribing Information and Medication Guide below. Voiceover: INDICATION: REYVOW is indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use: REYVOW is not indicated for the preventive treatment of migraine. REYVOW may cause significant driving impairment. Please see Important Safety Information for REYVOW and links to Prescribing Information and Medication Guide below.

See what's possible for your patients with REYVOW

EXPLORE EFFICACY DATA

References:

REYVOW [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC.
Rubio-Beltran E, Labastida-Ramirez A, Villalon CM, MaassenVanDenBrink A. Is selective 5-HT_1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018;186:88-97.
Vila-Pueyo M. Targeted 5-HT_1F therapies for migraine. Neurotherapeutics. 2018;15:291-303.
Clemow DB, Johnson KW, Hochstetler HM, Ossipov MH, Hake AM, Blumenfeld AM. Lasmiditan mechanism of action-review of a selective 5-HT_1F agonist. J Headache Pain. 2020;21:71.
Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97:553-622.
Ahn SK, Khalmuratova R, Jeon SY, et al. Colocalization of 5-HT_1F receptor and calcitonin gene-related peptide in rat vestibular nuclei. Neurosci Lett. 2009;465:151-156.

INDICATION AND USAGE

REYVOW is indicated for the acute treatment of migraine with or without aura in adults.

Limitations of Use: REYVOW is not indicated for the preventive treatment of migraine.

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS

Driving Impairment
REYVOW may cause significant driving impairment. In a driving study, administration of single 50 mg, 100 mg, or 200 mg doses of REYVOW significantly impaired subjects' ability to drive. Additionally, more sleepiness was reported at 8 hours following a single dose of REYVOW compared to placebo. Advise patients not to engage in potentially hazardous activities requiring complete mental alertness, such as driving a motor vehicle or operating machinery, for at least 8 hours after each dose of REYVOW. Patients who cannot follow this advice should not take REYVOW. Prescribers and patients should be aware that patients may not be able to assess their own driving competence and the degree of impairment caused by REYVOW.

Central Nervous System Depression
REYVOW may cause central nervous system (CNS) depression, including dizziness and sedation. Because of the potential for REYVOW to cause sedation, other cognitive and/or neuropsychiatric adverse reactions, and driving impairment, REYVOW should be used with caution if used in combination with alcohol or other CNS depressants. Patients should be warned against driving and other activities requiring complete mental alertness for at least 8 hours after REYVOW is taken.

Serotonin Syndrome
In clinical trials, reactions consistent with serotonin syndrome were reported in patients treated with REYVOW who were not taking any other drugs associated with serotonin syndrome. Serotonin syndrome may also occur with REYVOW during coadministration with serotonergic drugs. Serotonin syndrome symptoms may include mental status changes, autonomic instability, neuromuscular signs, and/or gastrointestinal signs and symptoms. The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue REYVOW if serotonin syndrome is suspected.

Medication Overuse Headache
Overuse of acute migraine drugs may lead to exacerbation of headache. Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients including withdrawal of the overused drugs and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.

ADVERSE REACTIONS

The most common adverse reactions associated with REYVOW (≥2% and greater than placebo in clinical studies) were dizziness, fatigue, paresthesia, sedation, nausea and/or vomiting, and muscle weakness.

ABUSE

REYVOW contains lasmiditan, a Schedule V controlled substance (C-V). REYVOW has abuse potential. Evaluate patients for risk of drug abuse and observe them for signs of lasmiditan misuse or abuse.

See Full Prescribing Information and Medication Guide.

LM HCP ISI 28SEP2020