﻿[music] Voice-over: Welcome
to Spotlight on Migraine, hosted by the Association of Migraine Disorders.
Join us for fresh perspectives by medical experts and advocates
as we explore the spectrum of migraine and dig deeper into this complex disease.
Dr. Deena Kuruvilla joins us to talk about lasmiditan, a new acute treatment for migraine.
She discusses results from lasmiditan research studies, how it works, efficacy, side effects,
dosing, and access. Dr. Deena Kuruvilla:
I'm Deena Kuruvilla. I am a neurologist and headache and facial pain specialist
at the Yale School of Medicine. I'm so glad that you all could join me today to discuss
lasmiditan, an exciting new rescue treatment for migraine. I really look
forward to going through some of this data today, some of the slides, and seeing how
lasmiditan fits into the other existing rescue therapies that we have. So let's get started.
So here on slide 2, these are priorities for migraine rescue treatments that patients report.
There have been surveys that have been sent out to migraine patients that specifically asked, "What
matters most to you about your rescue treatment, about your acute treatment?" And in those studies,
it was identified that around 87 percent of patients prioritized complete elimination of
pain and 83 percent of folks prioritized rapid onset for the relief of their headaches.
And so looking at these survey studies and seeing what patients really prioritize,
it was really interesting to see that that was incorporated into the clinical trials
for lasmiditan. So in the trial for lasmiditan, one of the primary end points is, What was the
percentage of patients who had complete elimination of their pain? And so we will
touch on that today and kind of see how did this trial match up to what patients really want.
So here on slide 3, I have some questions for us to answer today. So the first question is,
"How does lasmiditan treat migraine?" That's the biggest question. What is the mechanism? Why do
we think that it works? The second question is, "How do I know lasmiditan is effective?" We'll go
through some of that data as well. "What are the potential side effects of the medication? What
are the doses available?" and, "How do I get the medication?" What is the process that I probably
need to go through to obtain this medication? So we will touch on that today as well.
So how does lasmiditan treat migraine? So it is a first-in-class medication,
the first migraine rescue treatment that specifically works and activates the 5-HT1F
serotonin receptor. Thus far, triptans have been a tried-and-true treatment for migraine
since the early nineties, but they have a different mechanism of action. And so the
lasmiditan really works differently in order to provide a different mechanism for pain relief.
So up to this point, we've had triptans, but I think we all know that triptans have their
limitations. We typically don't use triptans in folks who have a history of cardiovascular
disease, a history of heart attack, history of stroke, uncontrolled diabetes, uncontrolled
hypertension, because triptans specifically work at the level of the blood vessel to
constrict the blood vessel. So that is one huge way that lasmiditan is differentiated
from triptans, and we're going to go into more of those details today.
We've found through basic science research that the 5-HT1F receptor is involved in pain
pathways. It's present in the central pain pathways and the peripheral pain pathways.
And activation at this receptor has been found to block pain pathways, to inhibit them, and also to
inhibit the release of specific neurotransmitters and neuropeptides. So that's just one idea on how
it may be helpful for folks who have migraine, as a rescue treatment.
So here on slide 5, this diagram specifically shows the differences between the triptans
and this new first-in-class medication, lasmiditan. So triptans are agonists at the 5-HT1B
and the 5-HT1D receptors, B for "blood vessel." So triptans can activate the blood vessels, because
these serotonin receptors are present on blood vessels, and triptans have less affinity for
5-HT1F, for that specific receptor. That's where lasmiditan comes in.
So you can see here the different receptors and the affinity of triptans and ditans for their
respective receptors. It's really, really what divides them and also
gives us a different mechanism, a different option for the rescue treatment of migraine.
This might be a medication that we consider -- lasmiditan -- in folks with a history of
cardiovascular disease, a history of stroke or heart attack, uncontrolled hypertension,
uncontrolled diabetes, because it doesn't work at the level of the blood vessel
as much as triptans do. So that's kind of a key takeaway from this slide.
So there were two large clinical studies specifically looking
at the rescue treatment of migraine in episodic migraine patients. So in patients who are having
less than 15 headache days a month, lasmiditan was studied. Lasmiditan was looked at across these two
specific trials, SPARTAN and SAMURAI, and we'll go over some of the differences between the two
trials. Basically, one included patients with a history of cardiovascular disease, history of
heart attack, stroke, deep-vein thrombosis, and one study did not include those patients. The
SAMURAI study did not include those patients. So across these two clinical trials, over 4,000
adult patients were enrolled. Forty-one percent had two or more cardiovascular risk factors.
Patients in the trial had to at least have migraine for one year
to be enrolled. And at baseline, patients had three to eight migraine attacks per month.
Patients were asked to take the study drug medication within
four hours of their headache starting and when the pain was moderate to severe.
So in the SPARTAN study, our study that included patients with cardiovascular disease, 50 mg,
100 mg, and 200 mg were included. In the SAMURAI study, the study where
cardiovascular patients were not included, 100 mg and 200 mg were specifically studied.
And so slide 7 here gives a graphical depiction of what patients asked for, what was important
to them -- pain freedom. When am I going to get pain freedom if I take this rescue medication?
And so this is a graphical depiction looking at the placebo dose, 50 mg dose, 100 mg dose,
and 200 mg dose. And according to this, the higher in the dose -- you can see with the 200 mg dose,
when compared with the lower doses and placebo, folks were much more likely
to have pain freedom at two hours, looking at the pooled data from these two studies.
So we can see here the time in hours to when patients had pain freedom -- so from hour 0 to
hour 2 -- so we can see that percentage kind of going up of pain freedom.
So slide 8 here, 31 to 35 percent of patients had pain freedom at two hours if the drug was
dosed from zero to two hours from the onset of migraine, when compared to the placebo
group, which was 19 percent. Twenty to thirty-six percent of patients had pain
freedom at two hours if the drug was dosed at that two-to-four-hour mark. Because, remember,
in the trial, patients were asked to take the drug within four hours of when their headache started,
when the pain was moderate to severe. So the 31 to 35 percent who had pain freedom at two hours,
they took the drug at zero to two hours since the migraine onset. Twenty to thirty-six percent who
had that pain freedom at two hours took the drug between hours 2 and 4 from the migraine onset,
and that's compared with placebo having 15 percent headache freedom at two hours in that group.
So the next slide focuses on the most bothersome symptom. So, so many migraine patients tell us,
"It's not just the pain that's bothering me. I have to be concerned about nausea.
I have to be concerned about photophobia. I have to be concerned about [phonophobia?].
So those other symptoms were looked at as well in this trial.
In this particular trial, they looked at what percentage of patients were able to achieve
complete freedom of their most bothersome symptom within two hours -- at that two-hour mark, right?
So we're seeing that with the most bothersome symptom,
around 40 to 49 percent of folks had complete freedom from their most bothersome symptom
at two hours if they took the 200 mg dose. We're seeing around 40 percent of folks
had complete freedom from the most bothersome symptom at two hours
if they took the 50 or the 100 mg dose. And we're seeing around 30 percent of folks had
complete freedom from the most bothersome symptom at two hours if they were in the placebo arm.
So it's just a nice way to be able to look at some of this information taken from both trials
and see, How can we translate that into real life? How likely are folks able to get rid of that
photophobia, sensitivity to light, sensitivity to loud noise, and nausea? It's very important.
So our next slide here focuses on side effects. We all want to know, "How likely am I to have side
effects to the medication?" When we're looking at dizziness, which was the most common side effect,
lightheadedness is the most common type of dizziness in these folks who have the side effect.
We do see this dose-dependent response. So as the dose goes higher,
folks may be more likely to have lightheadedness, have that dizziness. Nine percent of people who
took 50 mg of lasmiditan -- also known as Reyvow -- is the brand name, had dizziness. Fifteen
percent of folks had dizziness in the 100 mg arm, and 17 percent had dizziness in the 200 mg arm,
when compared to 3 percent in the placebo group that had the same dizziness.
Other side effects that people reported were fatigue, paresthesia, sedation, nausea or
vomiting, and muscle weakness, and I stated those in the order of how commonly they happen.
So things to be cautious about -- Reyvow was specifically studied in healthy people
to see if there was effects on sleepiness and driving ability, using a simulated driving test.
So Reyvow, lasmiditan, is a controlled substance and has to be prescribed by a doctor, and
there is a driving restriction on it based on these simulated driving studies that looked at
healthy people who took the medication. I advise patients not to drive or operate heavy machinery
for eight hours after taking the dose, and that's because they did find that folks
did have some difficulties with that simulated driving test and that folks were still sleepy
around that eight-hour mark after taking the medication. So that is extremely important. No
driving or operating heavy machinery for eight hours after taking it.
Dizziness was another common side effect, which we spoke about,
that I always tell folks about, to just watch out for. Serotonin syndrome -- just as we see with any
drug that works on serotonin receptors --with our antidepressant medications or with our triptans,
for example -- there's always a risk for serotonin syndrome, which is comprised of a constellation of
symptoms such as muscle stiffness, fever, changes in thinking. So I always ask people on follow-up
visits if they're having any of these symptoms, to make sure I'm not missing serotonin syndrome,
which is an emergency and should be evaluated right away in the emergency room.
I always counsel folks about medication overuse headache, not to use their as-needed
medications like Reyvow too much or you can end up having a much worse and continuous headache.
Allergy -- I always counsel folks about potential allergy with the medication.
And again, it is a scheduled substance, a controlled substance. And so there were higher
drug-liking scores with Reyvow, and so [it's?] just something to be cautious about. There could
be this risk of dependency. The drug-liking scores for Reyvow were lower than alprazolam,
but there is still that likability there, so just be cautious of that risk of dependence.
It is not approved in pregnancy and lactation so should not be considered in those cases.
So there are three dosing options for Reyvow -- we're here on slide 12 -- 50 mg, 100 mg,
and 200 mg. You can only take the drug once. It should not be repeated, because that
second dose was not shown to have any additional benefit. So no more than one dose in 24 hours.
Doesn't matter if you took the 50, the 100, or the 200; you cannot repeat the dose.
We have that driving restriction -- should not operate heavy machinery or drive for
eight hours after taking. And there is a savings card that's available for the drug.
So I usually prescribe the medication for my patients after having a pretty good
discussion -- lengthy discussion -- about how it works, the side effects, going over if they're
comfortable with it, and then I prescribe the medication. I always give them a co-pay card,
which is also available online, and they're able to activate that by calling the number on that
card. And then they can proceed to the pharmacy to try and get the medication at as low as a
zero-dollar co-pay for the following year for commercially insured patients.
So just a little tip there on how to be able to get the medication effectively and also how
to discuss the medication with your headache provider. Maybe Reyvow is right for you, and
maybe it's not, but it's certainly worth knowing about all these exciting migraine medications that
are coming out this year and all of them that are slated to come out in the coming years.
So I thank you so much for your attention today.
[music] Voice-over: Thank you for tuning in to Spotlight
on Migraine. For more information on migraine disease, please visit MigraineDisorders.org.