EEC 2026 | Emerging precision therapies reshaping the antiseizure medication landscape in epilepsy

It’s a very exciting time to be working with epilepsy and to be working against seizures because we have been treating seizures all our lives and still we see a lot of patients that do not get better or actually control their seizures and still have a lot of issues they probably have with the baseline etiology. So we’re transitioning now to a more biologically diverse role of medications, because prior to now, we would have medications that were either serendipitous findings, like valproate, or that actually would bind only to sodium channel blockers or would enhance GABAergic inhibition through direct GABA-A or GABA-B receptors and so forth. And now we’re seeing that this whole, I believe this whole bucket of medications are actually changing. They’re becoming more selective. They’re becoming new mechanisms, especially where targeting epileptogenesis or actually etiology itself. So I believe from that, for my review, that’s the main thing. And there are a lot of exciting molecules that I can talk to you about that are probably going to change the landscape of epilepsy treatment in the next few years. One of the most interesting talks in the European Epilepsy Congress was about azetukalner or AZK for close ones. That is a medication that actually targets the potassium channel, the KV7 potassium channel subfamily. So instead of closing these channels, we’re going to do something different. We’re going to open them. We used to have a medication that used to do this. It was taken out of the market a few years ago, but azetukalner is coming back, and it’s coming back big. So Professor Jacqueline French from NYU presented the results from X-TOLE2, and they were very exciting. What did she see? They saw that azetukalner at a dose of 25 milligrams, reduced seizures around 53%, comparing to 10% in placebo. So we had a response rate of around 42% comparing to placebo. That’s a great response rate. It actually showed that patients that were still on the open label, they would have an amazing result. 40% of these patients would have at least 12 months of seizure freedom and around 25 to 30% would have 24 months of seizure freedom. That’s something that we usually don’t see with pharmacoresistant patients that we have ever already saw with cenobamate. So we’re having a completely new mechanism of action, or as we could say, a rescued mechanism of action that opens channel blockers in neurons, especially during the refractory phase, and actually that’s been showing to have very few side effects. They have a few issues with neuropsychiatric adverse events, so they were doing a secondary analysis, but still they already submitted, I believe, in September, just after the European Congress, they submitted to the FDA an application to the medication to enter the market. So I believe this is the closest we have been to actually a new medication getting to the patients after fenfluramine or cenobamate. So that’s great news. We’re probably going to be using and talking a lot about azetukalner, in the next few years.

Another thing that I found very interesting, and now we’re talking about the DEEs, the developmental encephalopathies, epilepsy, and encephalopathy. So that we have a few medications that actually target this population. Relutrigine, that is actually from Praxis as well, is having the Phase III trial EMERALD. Right now, I believe they closed enrollment in August or September. So we’re probably going to have this information. So it works very closely to vormatrigine with a few differences in the sodium channel blockers that actually block. And relutrigine is probably going to be approved for SCN2A and SCN8A DEEs in December or early January. So it’s probably going to reach the market for within the next year or 2028. And it’s probably going to have a very nice, it’s going to be a very nice example of then functionally inactivating those sodium channel blockers, those sodium channel currents, the persistent ones. And we have then a few medications that were actually working, like fenfluramine, that actually block serotonergic receptors, the 5HT2A and 5HT2C, fenfluramine, but now we have bexicaserin that’s from a trial from Lundbeck, the DEEp SEA and DEEp OCEAN that are evaluating them in general DEEs, including Lennox-Gastaut syndrome, and also in Dravet syndrome. So, bexicaserin is going to inhibit this serotonergic receptor, and also blocking GABAergic, enhancing GABAergic inhibition for different mechanisms of action. That I think is amazing. And we already know fenfluramine works very nicely, but it has the cardiac issues that a patient has to have repeated echocardiograms every six months during the first two years and so forth. Bexicaserin is not going to have that issue because it does not affect the receptors A and B. So it will probably, it already has received a waiver for requiring a high monitoring system for cardiac events. So it’s going to be probably the benefits of fenfluramine without the possible cardiac effects. So I believe that’s going to be a very nice molecule that we’re going to talk about in the next few years.

And of course, then we have the, let’s just say, the best things that we have, then we can actually influence biology directly. We have a few medications that target mainly messenger RNA, like zorevunersen, that’s an oligonucleotide that actually tries to enhance the production of sodium channels in patients with Dravet syndrome. So in patients with Dravet syndrome, we know that more or less 80% of those will have SCN1A mutations, 1A mutations, and that most of them will make the sodium channel stop working. So there’s going to be loss of function. So this molecule actually enhances the production of sodium channels by the healthy allele. So you put more receptors within the inhibitory neurons that actually cause nervousness. So the results from the Phase I trial were just published, I believe, in what is now July, and they were amazing. And during the European Epilepsy Congress, Professor, I forgot her name, but she presented the results from an open label that was actually very, very nicely done that showed an improvement in developmental marks compared to a historical population. So just targeting that that we always dreamed about as epileptologists, that not only targeting networks, but actually targeting the whole brain and making the brain function better. So I believe those are going to change the field, because if that trial, the randomized trial will be positive, then we’ll have that definitely hallmark that we can change the natural history of these diseases, even without reducing spikes and reducing seizures and so forth. So I believe that it’s probably going to be the most exciting changes that we have on the field. And I talked about that a lot during my review, because we’re targeting not on seizures, we’re targeting quality of life and targeting quality of brain function. I believe that’s the most exciting news we can extract from the European Congress.

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