Emerging Migraine Treatments Challenge a Mature Market

Roy Moore of Clarivate’s market access team discussed the evolving migraine treatment landscape, highlighting the maturation of the acute and prophylactic markets, the emergence of new therapies such as triptan-COX-2 combinations, gepants, neuromuscular blockers, and monoclonal antibodies, and the challenges of integrating costly novel therapies amid generic competition and payer management pressures.

Key Takeaways:

• The migraine market is maturing, with recent approvals such as combination triptans, gepants, and neuromuscular blockers expanding both acute and preventive treatment options.
• Future development is centered on novel mechanisms—like neuromuscular blockers (eg, Xeomin) and monoclonal antibodies targeting specific neuropeptides—that aim to address unmet patient needs and improve sustained efficacy.
• Despite innovation, payer management and the rise of low-cost generics will push new therapies to later-line use, creating pricing and reimbursement hurdles for manufacturers.

Please introduce yourself by stating your name, title, and any relevant experience you’d like to share.

Roy Moore: Hello, everyone. My name is Roy Moore and I'm with the market access team here at Clarivate. I have 20 years of experience in US and global market access on the syndicated consulting side. I look forward to discussing migraine today.

Let’s start with an overview—what does the current migraine drug pipeline look like, and which therapeutic approaches or mechanisms of action are generating the most excitement right now?

Moore: Migraine is quite an interesting indication because, at least internally, we segment the population. We have the acute market—those suffering from migraine need to be treated right away—and then we, of course, have the prophylactic market. Those are the drugs you take to prevent migraines that are recurring.

Let's start with the first grouping, which are, again, the acute market. The pipeline has already come to a head. A lot of the newer therapies that we are looking at have actually just launched or been approved in the past year. We've seen some dynamic changes to this market in general. Triptans still dominate, but we've seen the development of additional triptans. There was one that was a combination triptan and COX-2 inhibitor called Symbravo. They launched in June. It's interesting because it targets multiple pathways in hopes of a more rapid onset of action. There's also an oral that will launch later this year in this class.

Now, of course, we've seen some growth in this market in general because we've seen the gepants get approved in the last 5 or so years. Those have had pretty good uptake in this population for those who are not responding to triptans. We are going to see continued development here as well. A couple of years ago, there was a Pfizer product that was a nasal spray that launched in 2023. So, obviously, we're seeing development there as well.

Lastly, for this market, we have derivatives. That's where the market's developed most recently. If you had asked us in the year, "Where do you see the market heading?" I would've pointed to this. We've seen drugs already approved for this population, including Atzumi, which is a nasal powder and device product, and then Brekiya, which has an autoinjector that's typically administered in the thigh. That's what we're seeing.

We do something different when it comes to the prophylactic market. We see different drugs that are used here, but some of the same issues are at play. There's early-line treatment, but then things tend to move on for those who aren't responding, and they tend to take other neuromuscular blockers like Botox, which we're all familiar with, and then, of course, we have the monoclonal antibodies.

For the pipeline going forward, we do see some development. It's probably 4 to 6 years out, but we do see [potential] with the neuromuscular blockers in development that we expect to come out later this decade. There's another monoclonal antibody that's in pipeline that's going to be unique in the sense that it targets a specific neuropeptide. So, we'll be monitoring that.

Those drugs are still in phase 2 development, so we don't have great data on them yet, but we'll be monitoring where that market develops.

Are there any candidates in mid- to late-stage development that stand out in terms of efficacy, safety, or novel mechanism—and how might these reshape the current treatment landscape for migraine prevention or acute management?

Moore: As I mentioned before, Atzumi was recently approved. It's an ergot derivative. It was approved in April. What's unique about it is that it's an intranasal delivery device. It could be interesting, but it'll probably serve a niche population. Again, these patients typically have to go through the triptans first. I'd say the same with the other ergot derivatives that have been approved in recent years.

Now, when it comes to the prophylactic markets, I mentioned before that there are some products in development. There's a neuromuscular blocking agent called Xeomin. It's interesting because it's an intramuscular injection administered every 3 months. What makes this product somewhat unique is that it's targeting both chronic migraine and episodic migraine, whereas Botox, which is the most commonly known drug for this class, is currently only indicated for chronic migraine.

There could be some development there, but it might also just be used for those patients who don't respond to or can't take Botox. They're also hoping that's it's formulation could neutralize the risk of antibodies being developed. This is important because if those antibodies develop, that reduces the efficacy over time—efficacy wanes. They're hoping, with this product, that it would offer an advantage over sustained benefit.

I mentioned before there's a monoclonal antibody. It's inhibiting the PACAP-38, which is known to cause migraines. There's not a lot to speak about right now because it's still in phase 2 trial and set to launch in 2031. We do know that it's an intravenous (IV) every 3 months. That's going to be interesting. What's going to happen is that this will probably be positioned for those who can't take gepants like Ubrevly.

How might they reshape the market? These are going to be later-line treatments, and the reason for that is because, with migraine, I don't want to say it's necessarily a fully mature market, but you do have early-line treatments that have been available for decades and are inexpensive. You have the triptans for the acute market, and then you have other classes, of course, for the prophylactic. These drugs will be coming in at the end. One of the reasons is that early-line treatments are effective and cheap, and these new drugs will most likely be coming out of price premium, so they'll be positioned later.

I don't necessarily think they'll reshape the initial market. It's just the later line treatments where you could see some development.

How could emerging therapies—such as next-generation CGRP antagonists, neuromodulation devices, or combination regimens—affect the positioning of existing treatments like triptans, gepants, and monoclonal antibodies?

Moore: They add competition, of course. This is not an indication where they've already solved it. There's still need for treatment. There's unmet need in this indication, as there is for so many. How will these effect existing treatments?

As I mentioned before, the market's somewhat mature because you do have low-cost generics, like the triptans, for instance. It's not going to affect them at all because those will always be preferred. Sumatriptan is, I believe, $4 per pill. That's pretty hard for a new therapy to beat as far as price. Those won't be affected. It's going to be the later drugs—for instance, the neuromuscular blockers, the monoclonal antibodies, etc.

If they're all branded and there is not a generic competition, you could just see price competition. You could see more active rebating, more active contracting, that sort of thing. But I feel that the treatment paradigm is slowly going to follow through the lower-cost generics first and then move into these other lines of treatment where the costs escalate.

From your perspective, what types of data—clinical outcomes, safety profiles, biomarkers, patient-reported outcomes, or cost-effectiveness—should clinicians, payers, and researchers be watching most closely as new migraine treatments move through the pipeline?

Moore: The thing with migraine that makes it a handy indication is that it's easy to measure and easy to track. The first thing that comes to mind is number of migraine attacks. That's the big one that's easy to track when it comes to clinical trials, but also in the real-world setting. There's also going to be importance in sustained freedom from pain or most burdensome symptom scores and that sort of thing over a certain time period, maybe 2 to 48 hours. We'd be looking at patient-reported outcomes there. Those would be things that would be tracked. Time to effect would be highly important to our clinicians and patients because migraines are a debilitating experience. You want those cleared up as fast as possible.

Adverse events would be at top of mind because adverse events could lead to hospitalization or trips to the emergency room (ER), and that's going to come at a cost to payers. That's something that they would be really interested in seeing. Showing clinical benefit over what's currently available is important, but it may be difficult if you have trials that are built around non-inferiority as opposed to superiority.

The only way you're going to be able to compete is if you have the better price, unless you can have some other data that are going to be compelling to payers. Can you show a benefit in terms of ER visits or hospitalization? That is a message that'll resonate to them because they can compute that into their models and understand the value of the product at that point.

What are the main challenges to integrating novel migraine therapies into clinical practice—whether related to access, adherence, or health system readiness—and what innovations do you anticipate over the next 5 to 10 years in migraine management?

Moore: First of all, it's already a pretty managed space. That's not surprising. Anytime you have a chronic indication where you have low-cost generics as an option, payers are going to move you through that. The nice things about migraine treatments are that we have a lot of them and they're all pretty good.

There are drawbacks to some. Obviously, some patients can't receive certain drugs. We're in a good spot for that, but I'll say it's going to be a challenge for manufacturers of new therapies.

When the new therapies come out, if they're approved, they will probably be reimbursed by payers, but they will be reimbursed for later lines of treatment, as I mentioned before. I'm talking specifically about the prophylaxis market. This would come after early-line treatments and even some of the existing products, because, again, they'll have a shorter track record and there could be contracting at play.

They'll be used in later line, usually through some sort of payer management, like a prior authorization. We also see a challenge, of course, in the sense that a lot of these drugs that are currently being used—such as the neuromusculars, Ajovy, Emgality, Vyepti, and Amovigy—are expected to go generic probably in the next 6 years and later. That's going to create downward pressure for the market. That's going to create challenges as well.

With the monoclonal antibodies, they have to be administered in a site where they can do infusions. That does create some challenges, but those are easy to overcome as we had done with other indications. But it's going to be around the downward pressure put on new products by either existing products that are already generic or ones that will go generic over the next several years.

Payers will tell you that—and I know some of the products are in development—they’re looking at novel mechanisms of action (MOAs). That monoclonal antibody I mentioned before is targeting a specific neuropeptide. That's unique and that's the thing payers are receptive to because they will say, "There are some patients that will respond to current treatment, and we always want to give an option for those people to receive care."

Those are some of the things that the payers will be receptive to. Of course, it'll help if you have data showing that you can actually have better benefits over what's currently available.