S3:Ep31 – Trudhesa: A New Delivery System for DHE

TRANSCRIPT:

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.

Stick with us as Dr. Jack Schim joins us to discuss Trudhesa, a newly approved abortive migraine treatment option. Dr. Schim explains the technology behind this new administration method for dihydroergotamine nasal spray, as well as efficacy and safety data.

Dr. Jack Schim: Welcome and thank you for joining us so that I can share with you some important new information about a brand-new option for our patients with migraine, Trudhesa. Trudhesa is DHE nasal spray, dihydroergotamine mesylate. This is a medicine indicated for the treatment of migraine acutely in adults, meaning it’s not a preventive. This is something very different for treating a headache, migraine headache. 

First, my disclosures. I work closely with a number of pharmaceutical companies that help develop new medications and treatments in the migraine world. Almost all of my practice is headache related, migraine related, and has been so for many years. 

When we talk about new medicines — or, for that matter, when we talk about any medicines — it’s important to have a clear understanding, fair balance. And so this is a little bit of the safety information that’s worth knowing about, and I’m just going to highlight one or two things. 

First of all, DHE 45 has a blood-vessel-constrictive capability, and, therefore, it’s important that, first of all, you let your doctor know about your migraine headaches and make sure that they’re aware of your other medical conditions, as I’m guessing they are likely to be. But things like uncontrolled high blood pressure and so forth would be reasons to probably not use Trudhesa.

There is the potential for safety concerns and drug-drug interactions with certain medicines that share the same metabolic pathway in the liver, which is known as the CYP3A4 pathway. And you can see a couple of the sorts of things that might be an interaction. For example, certain antibiotics, certain antifungal medications shouldn’t be used if someone is using Trudhesa. 

Well, the reason we’re here is that, of course, our existing treatments are really not ideal for everybody. And just a couple of facts here, first of all from a study done way back in 2007 by Dr. Marcelo Bigal. And he assessed patients’ success rates with standard oral migraine meds, things like the triptans that have been around and been helpful for many years, the problem being that they don’t always get people pain-free, be rapid, keep people’s headache gone. And so, in fact, four out of five people said that they’d be interested in trying something new. 

Much more recently, Dr. Lipton published just two years ago a survey of almost 4,000 US residents who had migraine who were taking one or another acute oral migraine prescription med. And as you can see, almost 96 percent said they’re not completely satisfied, and that leads to, Well, what are the reasons? And the reasons are multiple. 

First of all, migraine is a complicated disease. It’s not just a headache, as I know that you’re very aware of, but it’s been known to be a — we’ll call it “sick headache” for a long time. And what we mean there is the gut, the GI connection, is very well established. 

First of all, it’s actually part of the diagnostic criteria of migraine. Nausea is common, loss of appetite, maybe even diarrhea. But beyond that, even if someone isn’t having nausea, your gut can kind of be at a standstill. Dr. [inaudible] has been publishing information about this for about 15 years. And if your gut isn’t working well, the absorption of oral medicines is not going to be reliable. 

Secondly, many of our medicines really work only on one pathway within the brain, and migraine is more complicated than that. And, in fact, during different attacks or different phases of an attack, different circuits and different neurotransmitters can be involved, and so medication that works on multiple pathways, such as DHE, offers a new option there. 

And then, on top of that, we know that with many of our existing medicines, if you don’t catch the headache right away, your success rates are not going to be very good. The thought that I explain to my patients with the standard medicines is you have to catch it while you have a window of opportunity. And if you get past that, that window may close on your fingers and a non-oral medicine might be the appropriate solution there. 

Trudhesa might be that medicine. It’s the appropriate thing to consider if you need something that is rapid, if your headaches build quickly. If you have nausea, you need something that’s not going to get absorbed through the gut but is going to get absorbed differently — in this case, through the nasal airway, nasal [inaudible]. And if you need something that lasts a long time, that keeps your headache gone once it’s gone, DHE can offer that.

Trudhesa is delivered with what’s called the POD system, and that’s illustrated here. This is a manually operated, self-propelled — meaning there’s a propellant involved — easy-to-use device that delivers DHE 45 in a way that is well absorbed. This improves the bioavailability because standard preparations tend to trickle down the back of the throat, and they taste terrible. They may not have reliable results. And the vast majority of people in the trials who were surveyed, 84 percent, said this was easy to use. 

When medicines are going through the gut and absorbed in the gut, many of them, including DHE, are metabolized in the liver, and that can clear it off so quickly that you may not actually get good results. With this delivery system, that is not an issue. This avoids the issues about nausea, the autonomic dysfunction that is very common in migraine, because it is non-oral and it delivers it in a very different way, in the upper nasal space.

So let me show you what I’m talking about, then. First of all, our standard nasal treatments are illustrated on the left side of the slide. What happens when we use one of those? It sprays; it basically goes into the lower portion of the airway there, the nasal passage; and a lot of it tends to trickle down the back of the throat. 

So the downsides of that are, number one, it’s not getting rapid absorption because it’s going through the gut. Number two, they often taste terrible. And so it has a bad outcome in that sense because the last thing we would want, of course — this for a medicine being used to treat migraine, which has nausea — to make your stomach feel even worse.

Trudhesa has a different approach. This has a process or a delivery device that sprays it in a gentle plume, and that’s followed by a little bit more of the propellant that carries it into the upper portion of the nasal passage, which is very vascular. That way it stays there, it gets absorbed, and has quick results, sustained results. 

Next I’d like to share with you some information directly from the standard nasal DHE. So, first of all, in their clinical trials — and this is the basis for the approval of Trudhesa — the things that showed up as coming up once the treatment was done are listed there: rhinitis, runniness in the nose, nausea. Those are the worst-case scenarios, let’s say. And you can see there it is compared to placebo. Other things that result in potentially someone stopping treatment: dizziness, swelling in the face. As you can see, these are very uncommon outcomes. 

In the basic clinical trials of the original approval of nasal DHE 45, you can see the outcomes. First of all, what we’re really looking for when we treat someone’s headache, when you’re treating your headaches, is for the headache to respond quickly. Response means going from bad — from moderate or severe — down to none or mild. So we see here different numbers in different studies, but, in fact, very good results. And something that is rather different from standard things like the triptans is that the results get better over time. So, two hours, up to 61 percent had results and response. By four hours, that had climbed up even further. 

Trudhesa was studied in what was called the STOP 301 Study, a big clinical trial. And this was such that people were allowed to use the medication as needed up to two doses in a day; typically would wait an hour in between because you want see, you know, did it work; and up to three times, three days within a week. What we saw there is that nausea occurred in an infrequent fraction. Less than 1 percent of the total of over 6,000 doses resulted in nausea over a 52-week study. There was no associated drowsiness or dizziness.

You shouldn’t take it when you’re pregnant. We know that DHE 45 — DHE is the product in Trudhesa — is not to be taken during pregnancy or breastfeeding. And, once again, you should double-check with your doctor, of course, and make sure that you don’t have cardiovascular risk factors that would be a reason not to use the medication. 

Well, what does it really mean for you? As I said, the vast majority of people found that this can work rapidly; have sustained, steady results; and, therefore, you can say — not everyone’s going to get results, of course, in 15 minutes, but this is absorbed very rapidly, and that can start quickly.

Pain relief can last up to two days with a single dose. It’s important, of course, to have it at the ready. It’s not going to do any good if it’s in the office and you’re at home, but, in fact, you can use it wherever you are. This is not a medicine that is controlled substance. There are no specific driving limitations in regards to it. Obviously, you’re going have to try it for yourself to see how well it works, but I think that is a reasonable thing. 

Dosing is rather straightforward. The term is “DIRECT.” Determine whether everything’s ready to go. Be sure that you’re having a migraine. Assemble the device, quite simple. Prime it. You’re going to prime it four times so that the device is ready to go. Have your head straight up. Put it into the nostril, one spray on one side, one spray on the other side, and then you can toss it. It is a disposable device. 

As far as getting it, well, not complicated. For commercially insured patients, your doctor can prescribe this to the Trudhesa Savings Program. That means you don’t have to deal with a co-pay card — that’s applied automatically within the system — and it will be delivered and shipped to you directly, no charge for that. 

So be direct. Ask your doctor about Trudhesa. It works even if you’re late into an attack. That’s important because we can’t always catch our migraines at the onset. It’s important to have something that works even if you couldn’t catch it at the very beginning. The results are reliable. The absorption is consistent. It will work when the migraine hasn’t gone away.

[music]

Voice-over: Thank you for tuning in to Spotlight on Migraine. For more information on migraine disease, please visit MigraineDisorders.org.


*The contents of this podcast are intended for general informational purposes only and do not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The speaker does not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.