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.

This episode is brought to you by our generous sponsor, Biohaven Pharmaceuticals.

Join us for a presentation by Dr. Roni Sharon about the newly approved Relivion neuromodulation device for the treatment of migraine. Dr. Sharon talks about how the device works to reduce migraine symptoms, their phone app that accompanies the device, efficacy, stats, and more.

Dr. Roni Sharon: Hi, my name is Roni Sharon. I’m a neurologist and headache specialist. Thank you for the opportunity to present today. Today I’ll be presenting the Relivion device for the abortive treatment of migraine headache.

Disclosures — so I’m a consultant for multiple companies.

I always like to start by talking about how an exciting time it is for headache — for headache doctors, for headache patients. We have new and exciting research coming out all the time. We have new classes of medications, therapies, neuromodulatory devices that are really changing the lives of so many more of our patients. 

We’re able to improve quality of life like we never have before. With all these new treatments that we have available, we see a lot more awareness, a lot more people coming in the door and getting the right diagnosis of migraine, which means that we can really fit the right treatments for them. And there’s more things on the way.

Despite that, there is many treatments available for migraine, which means that nothing is perfect, and there’s still a huge unmet need. We have a lot of patients — and we know them — that prefer nondrug therapies. They’re very sensitive to medications. As a matter of fact, one of our biggest challenges is that our patients hate taking therapy, they hate taking medications, and they wait to see how bad their headache gets. And that’s the time where it’s the golden hour to try to treat, and then it becomes much harder to treat. 

We have patients that have contraindications to pharmacotherapies, and they can’t take certain medications, or they respond poorly in terms of efficacy or in terms of tolerability. So there is a big unmet need, and neuromodulation can actually help many of those patients.

So now I’ll introduce the Relivion device. It’s the first noninvasive, multichannel brain neuromodulatory system. Prior to the Relivion, we had stimulators that were invasively placed or we had other devices that targeted partially the trigeminal system, whether it’s the devices that only hit the supraorbital area or similar ones to that.

The way that it works — so it actually hits the trigeminal nerves that make me the most money — so the occipital nerve, the supraorbital nerve, the supratrochlear nerve — all at once. It has different leads. So it has four electrodes in the front and two in the back. It’s a device you put around, very comfortable for patients, and it kind of diversifies the neurostimulation and hits all the different channels the same. So it’s actually a very comfortable experience for patients.

From the headset, it gets uploaded to the cloud. The patient has an app, and then it can reach the doctor. And the doctor can actually get a lot of different information from the app itself in terms of treatment time, how long the treatment is, the intensity of the treatment — because it’s individualized and optimized, so patients can actually change a setting to different levels of intensity — how much it’s helping, if it’s giving pain relief, is leading to pain freedom. 

And then we can get more background information about the patient’s migraines in terms of triggers that might be causing their migraines, what are the leading triggers; if they’re taking medication, how much medication they’re taking; if they’re getting headaches that they’re not using the treatment for; what days of the week; weather, if that’s a factor; holidays. And what we can do with that data is we can actually learn a lot about the patient, learn about their migraines, and then individualize therapy, identify their migraines, provide better lifestyle changes and feedback to patients, ultimately reducing their migraine burden. So the app can actually be very helpful in understanding their migraines more.

So in terms of the studies that were done until now, the first study that they did was a small EU clinical study. It was prospective, randomized, and double-blind. Basically, they looked at the pain score. Fifty-five enrolled subjects, 20 to 58 years old. Basically what you would see with our classic migraineurs, so a majority of women. It was episodic migraine. The treatment duration was 60 minutes at the onset of an acute episode of migraine. Of course, this was adults only, 18 years and older.

So what do we see? So we see pain freedom in two hours. That’s one of the standard measurements that we use in the abortive treatment of migraine. And we see a big difference between the actual treatment arm and the sham. Forty-one point seven achieved pain freedom at two hours, as opposed to 20 percent. That’s a therapeutic gain of 21.7. Forty-one point seven is a very high number. I think that’s higher than what we see with any of the oral therapies that we have. 

In patients with severe or moderate pain at baseline, we see even better results, so 42.9, as opposed to a sham of 10.5. So you see a greater disparity. And the therapeutic gain is 32.4 percent. And, again, these are really efficacious numbers that we see in two hours. I can’t think of any triptans that achieve this.

Then they had their pivotal trial, which is the RIME study, so prospective, double-blind, randomized, placebo-controlled, multicenter study. Originally, they had 187 enrolled subjects. Of course, doing a trial in the time of the COVID pandemic is not so easy. Ultimately, 131 were included in the analysis. It was 20 to 70.5 years of age, actually higher than what we see in other studies, because a lot of studies really limit it to 65. The study duration was 16 weeks, and the overall enrollment period was 20 months. 

Just to summarize the outcome already, it met all of its primary and secondary endpoints, and the FDA cleared the device in February of 2021 despite the smaller sample size than was anticipated. Originally, they were supposed to do 187.

Just to talk about the patient population, mostly women, patients with episodic migraine, really what we see in our clinics every day.

When we look at pain relief at two hours, we see 60 percent pain relief, as opposed to 37 for sham, so a difference of 23 percent in terms of the therapeutic gain. When we get to pain freedom — and I think these are unbelievable numbers; I was very impressed by this — we see a pain freedom of 46 percent, as opposed to 12 percent for sham, so huge difference and a big therapeutic gain. 

When we look at most-bothersome symptoms, freedom at two hours, a very, very impressive number of 75, as opposed to 47 percent, so both statistically significant and very, very impressive. 

In terms of exploratory endpoints and what the FDA is looking for, they’re looking for decrease in pain and most-bothersome symptoms. Forty-seven percent as opposed to 11 percent. Really impressive numbers.

I like this slide a lot because this actually compares the Relivion device not just to other neuromodulatory devices in terms of superiority, but also to triptans. When we look at triptans, when we look at the treatment landscape, here we see 34, you know, proportion of patients achieving pain freedom, whereas 42.9 to 46 percent in the SP-301 or the RIME trial. So, much better than what we’re seeing with triptans or oral therapies, and that’s very impressive.

Something that I conducted myself, we did an open-label retrospective study looking at patients for the preventive treatment of migraine. So we saw the significant and impressive data for the abortive treatment of migraine. We wanted to look at how it was preventively and how it looks in the real world in terms of patients with chronic migraine, patients with medication overuse headache, patients with a significant migraine burden, even patients who are suffering from migraine every single day.

Twenty-one patients, high-frequency episodic migraine or chronic migraine, so a difficult-to-treat population. Patients who have been on multiple preventive therapies before. They received 20-minute preventive treatments, or daily treatments, and then we actually [inaudible] with it a little bit in patients receiving it five days a week as opposed to seven days a week, but on a regular basis in addition to the abortive treatments that they would use. The twenty minute was the preventive treatment, and then they were using it for 45 minutes for the abortive treatment.

And in terms of our primary endpoints, we wanted to see a decrease in headache frequency. We also wanted to see pain relief, pain freedom, amount of medications they were taking, and of course improvements in quality of life. 

In terms of responder rate, we were looking for a 50 percent reduction in monthly headache days, and, of course, we were looking for safety and tolerability. One thing I did not mention, the device was very safe and well tolerated for all of the patients in the SP-301 and RIME trial. That was consistent and what we expect for neuromodulatory devices that are noninvasive.

Looking at the patient population here, 86 percent female. They had 14.6 in terms of average migraine days. Fifty-seven percent of the patients were chronic migraine, and the vast majority were high-frequency episodic migraine.

So looking at the reduction in headache frequency, again, very, very impressive numbers. We see a baseline of 14.6 reducing 10 days, so a 67 percent reduction in their headache frequency by the third month to 4.6, and that was very impressive. 

What we saw, which was also great, is that it works for the vast majority of patients. So 86 percent of patients had at least a reduction of 50 percent in their monthly headache days. So, across the board, it was working for practically all of the patients. 

Here we see the individualized pattern of all the patients, of the 21 patients. Everyone had a reduction. Only three didn’t have a reduction of at least 50 percent. And then we see that patients had quite a dramatic reduction, so, many days of their life they got back to enjoying and not thinking about their headaches.

In terms of safety, as I mentioned before, very good safety profile. In terms of serious adverse events, nothing. We had one case of a minor skin irritation. Besides that, it’s a very favorable tolerability profile across all the studies that were done so far and what we’re seeing in the real world.

In terms of contraindications, one very important one is to not use it in the bath or shower. But in terms of the exclusion criteria, we did exclude people who did have intracranial surgery, and you see all the contraindications we have here. Of course, we excluded patients who were pregnant, with serious psychiatric history, and other exclusions. In terms of contraindications, metal implants, a recent brain or facial trauma, and you can see the warnings here.

Just to conclude, I think that we see from the pivotal trial and the trial before, we have tremendous efficacy in terms of the abortive treatment of migraine and some promising early data for the preventive treatment of migraine. We’ll see what’s coming. And thank you very much.

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

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