Exploring the Impact of Early CGRP Therapy Initiation on Migraine Treatment
Belinda Fenty, MBBS
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Belinda Fenty, MBBS: My name is Belinda Fenty and I'm a contract medical monitor with Lindus Health but I've worked in clinical trials for over 10 years across all of the phases working with healthy volunteers through different patient trials. Everything from common diseases like asthma to really rare diseases like amyloidosis. And I was lucky enough to work on a migraine study. I'll tell you why I was lucky maybe a bit later.
Please share an overview of notable recent advancements in migraine treatment.
Fenty: I think it's an amazing time for migraine treatment. There are a lot of new advances and the study that I was lucky to work on was the DELIVER trial here in London. It was for an approved drug, it was already approved in the states, eptinezumab, but it hadn't yet been approved in England. [It] had been approved in Europe. But what this meant was that I was working on a study where the patients were only able to access this monoclonal antibody via the trial that I was on. And it's the first trial where I was able to see some people's lives being transformed in front of me because these were patients who had chronic migraines mostly. We're talking over 15 headache days a month and severely impacting their lives, affecting their social lives, family lives, work lives. And talking to the patients I could see that actually. What they found is- because they've been suffering for many years- the people around them get tired of them being in pain so there is no longer any compassion for it. In the trial, some patients did have a remarkable reduction in the number of migraine days that they were having. It literally was life changing. And I felt sorry, I remember feeling sorry for 1 patient because when her participation ended, it hadn't been approved yet by NHS England, but had by NHS Scotland, but it meant that she had no access and she was seriously contemplating moving up to Scotland as a result of it. Thankfully, it has now been approved in England, but that was amazing.
You've got these injections like that are transformative because they're given as an IV infusion once every 3 months. So instead of having daily medications or having overuse of medications which can worsen your headaches and migraines, you've got this 1 infusion that hopefully, if you're lucky, if you're one of the responders, one of the roughly 60% of people who respond could reduce your severity by 50% or even more like in this particular patient's case, it almost fully resolves her migraines.
There's also the gepants and you can have oral, they also work on CGRP. And these 2 types, these CGRP therapies, are specific which is great. There has there's been a lot of work on neuropeptides and there's the PACAPs and the CGRP peptides that the work is being done on. We don't yet have an approved drug for the PACAPs but there's research going on into at the moment so that is exciting. And then aside from those sorts of medications, you've also got your neuromodulator devices, which are pretty exciting as well, things like CEFALY. That one works on the trigeminal nerve and it's looking better at preventing than treatment, although it does help some people. I think it's something like roughly 20 or 30% during. And also gammaCore, which is used on the vagus nerve. Those avoid medications altogether or at least reduce the amount of medications that you might need to use, so that's very exciting.
And of course, now we're in a digital age and there are apps and you can track your headaches, you can look at potential triggers, you can monitor the response of your migraines to various medications or interventions. And I think this is helping people feel more ownership over their condition and get a greater understanding of their unique response to medications, which hopefully leads us down that path of more personalized medicine.
What are some common barriers patients face when trying to access CGRP therapies and how can providers help address these challenges?
Fenty: There are a lot of barriers and of course, I know you’re a global show, I'll tell you a bit about my experience here in the UK. Number 1 is that they're very expensive. This is more of a global issue. One injection of eptinezumab costs about £1400, approximately. That is prohibitive worldwide. And we're going to have, at some point, generics or something that hopefully can come into play or some global collaborations or something to reduce the cost of this. But even in countries where you can't, you do have access to it like here in the UK. You can see that policy is very important in determining who gets access because the patient that I was talking about, she couldn't get access in England. But had she got a train up north and moved up to Scotland, suddenly she'd have access. That doesn't really seem fair but because it is expensive there are these sort of systemic differences that make a difference in the treatment of different patients.
And also stemming from that, because it is expensive, the eligibility criteria for receiving it then becomes more challenging to fulfill. Because you need to have a certain number of migraines a month. You need to have, with some of the medications, tried a certain amount of other medications. With eptinezumab, you need to have tried and failed 3 preventative treatments. With the oral ones, you need to have tried a couple of different triptans through Mediplan, anyway. And not only that, it's an IV infusion. It's only given here by specialists, so you need to be referred to a specialist. And the waiting lists in the UK are very long. That relies on you going to see your primary care physician about your migraine in the first place. And then persisting, getting something, it not working, going back, getting something, it not working, going back, getting something, it not working, going back, then there you go, you've got it, you're 3. And then you need to be referred. Then you're waiting. And then maybe finally you get an appointment. But do you meet their criteria? Maybe you don't. If these medications were less expensive, then the access would improve. On top of that there's the medical eligibility, so yeah you need to meet all of the criteria.
Migraines are very complex and often associated with other comorbidities, particularly depression and anxiety, and actually maybe if you're going on one of the antidepressants that they sometimes use hopefully could have some benefit. But they're very complex and you also could go through all of that and you might be one of the 40% of non-responders. Which is why it's great that there is ongoing research into other targets. And I know they're looking at the gut-brain axis as well. We've spoken about the systemic barriers, the medical edge ability, the financial barriers, also the barrier of education. If a patient doesn't know they have they're migraines and all doesn't know that there are great new treatments available then that's already a barrier to access. Providers can engage with their patients if they're lucky enough to see their patients and delve deeper into those headaches. “Oh, doc I've got a headache” might not just be a headache, it might be a migraine, so if the physician has the time they could delve into that and make sure that the patient's getting optimized in their treatment and getting fully reviewed.
What are the potential side effects of CGRP therapies? In what ways may CGRP therapies impact patient outcomes and quality of life compared to other migraine treatments?
Fenty: I was lucky enough to witness the amazing ways that CGRP therapies can help. And it's not that way with everyone, as I've kind of said, you might be one of the 40% of non-responders. But I did see people whose lives were completely changed. I remember 1 patient who was like, “Yeah, I finally feel myself again.” That not only changes them, it also changes the people around them and their relationships with the people around them and their ability to work.
We know that migraines can be absolutely debilitating. You can spend more than half of your month in bed, full days in dark in bed. That's an awful quality of life. Even if you have a 50% reduction, that's already substantial, that's great. And if you're lucky, like the few patients that I remember who had gone down to maybe like 1 a month from over 50, from about a decade of regular migraines and headaches. That is completely life changing. If you're having a quarterly infusion then the convenience of that is amazing. Adherence is high, you no longer need to have all of these oral treatments or painkillers that can actually amplify your migraine issue. And they're very well tolerated.
There of course can be, as with any medications, side effects. Rarely, you could get a hypersensitivity reaction. More commonly an injection site reaction, some redness or swelling and heat in the area of the infusion. But again, that's a small price to pay for that sort of treatment. Some people feel fatigued but, on the flip side of that, people with migraines tend to feel very washed out and fatigued anyway after a migraine and during. And constipation could be a problem as well. But for the most part, they appeared to be well tolerated. They are relatively new. The first ever one that I’m aware of was approved in 2018 in the states. So that's really new in the lifetime of medications. We are lacking the long-term data about the effects, but it's looking very promising.
Where do you anticipate the most growth in the future of migraine treatment?
Fenty: It's pretty exciting to be in a field that is so rapidly evolving. If we look at CGRP, that was discovered around 1982, I think roughly. Don't quote me on that, but roughly. And from 1982 to 2018, the release of medication over almost 40 years, not quite. But whereas the PACAPs were sort of shown to trigger the migraines in 2007, it's a little bit behind compared to CGRP therapies. But there's research being done into it and it's looking good and it's following a similar sort of model. I see and I hope that the more research that's done with the PACAPs, the more likely we are to get novel treatments in those areas that hopefully can help the people who don't respond to all of the other treatments.
I see us going towards more personalized medicine. Out of the armory of treatments that there are for migraine, none of them are at 100%. Particularly in terms of prevention. The triptans are good at- pretty high, I think, it's something like 70%- at terminating or reducing the severity in an acute migraine. But the point is there is this unmet need and people have different types of migraines. I think the more we understand about migraines, the more we will go towards this personalized treatment. “Okay, what's good for this person, what's good for that person, are going to have more preventative treatments?” And I think we'll probably be incorporating AI and digital solutions and these neuromodulatory devices as well and getting a deep understanding of the different causes and what works for each individual.
