Paul George, MD, PhD, FAAN, associate professor in the Department of Neurology and Neurological Sciences at Stanford University, Chair of the AAN Science Committee

Hi, I'm Paul George. I'm a vascular neurologist at Stanford University and in charge of the science, the chair of the Science Committee for the AAN.

This year has been another great meeting. A lot of people, no official attendance numbers yet, but all of the courses and science platform sessions and plenaries have really had a good buzz and a lot of full rooms.

Neurology is just advancing so quickly that there's always a lot of great new items at the conference and you know in topics ranging from headache to Alzheimer's disease to movement disorders to stroke and a lot of the areas kind of cross all those different disease types.

I think this meeting has been full of phase 3 trials in the plenary sessions

There's been kind of first in class treatments, for therapies, for autoimmune diseases like MOGAD. And that'll be a first treatment for that disease specifically and also could have impact across autoimmune disease which we're learning more and more about each year.

And then, another interesting phase 2 study that actually also might lead to new indications for

CAR T- Cell therapy and stiff person syndrome. And so that's another kind of immune response disease that the immune system can be reset with CAR T-Cell therapy.

I think that’s an area where we get a lot of questions from our patients about the GLP-1 type therapies, obviously widespread use now for diabetes and obesity. And so, there's been a lot of interest in, ‘Do they have other effects outside helping with patients with diabetes?’ And so, we actually had a plenary to start off the conference on Saturday. There was a controversy. Are there effects of the GLP-1s directly on the brain? Or is it all beneficial effects from kind of better diabetes control and weight loss, which we'll take both, but it's interesting to see if there's direct brain effects.

And so, there's been a few trials that haven't shown the GLP-1s in patients, outside of diabetic patients, that they help with Alzheimer's and those type, or neurodegenerative diseases like Parkinson's, too. But I think that those are early trials.

And so, I think that mechanisms for direct brain effects of GLP-1s are still being explored and understood, and so I think we're just at the beginning of that story. Do they have effects outside of just the diabetic effects?

Phase 3 X-TOLE2 Clinical Trial Results Evaluating Novel Epilepsy Treatment

Jacqueline French, MD, Director, Epilepsy Study Consortium; Professor of Neurology, NYU Grossman School of Medicine, NYU Langone Health

I'm Jacqueline French. I am the director of the Epilepsy Study Consortium, which is a non-profit that works with industry to improve the conduct of trials and also a professor of neurology at NYU Langone Health.

We presented the very exciting results of the phase 3 trial for a drug that is an anti-seizure medicine called azetukalner . It's a little bit of a mouthful. It is a KV7 potassium channel opener, which is a relatively novel mechanism of action for drugs in the epilepsy space.

And as commonly we see with these phase 3 trials, we take patients with treatment-resistant epilepsy and in this particular case, focal epilepsy, I should say. And in this case, they were particularly treatment- resistant, having at least four seizures a month.

We follow them for about eight weeks in a baseline to make sure we understand the seizure frequency because everybody's going to be compared to their own past seizure frequency. And then they get randomized.

And in this case, it was two doses versus placebo. It was a 15-milligram dose and a 25-milligram dose. And it was randomized one-to-one-to one, about 125 people in each of the arms.

We then followed them for 12 weeks, about three months. And after that, they had the option of going into an open-label extension.

And the nice and interesting thing about this particular drug is that it was started at the full dose from day one. So, there was no titration required.

The overall outcome measure was obviously looking at the outcome over the entire 12 weeks. But a very interesting secondary outcome was looking at what happened after one week, because we all know with epilepsy the faster you can get people under control, the better off you are. And at one week, there was already a statistically significant reduction in seizures, quite substantial.

So overall, when you look at the reduction, which was the primary endpoint, the median percent reduction in monthly seizures, the placebo arms had had a 10% reduction. We always see a placebo responder rate, this was actually less than we usually see, so that was nice.

And then the 15 milligram arm had a 34% reduction, and the 25 milligram arm had a 53% reduction.

When you look at what was the outcome at one week. You can see a 33% reduction at the 15 milligram and a 45% reduction at the 25 milligrams. So already quite close to the overall reduction. So again, that was really nice.

And in terms of dropout, because safety is obviously the other thing we pay very close attention to in these trials, overall, the drug, particularly at the 15 milligram dose, was very well tolerated with dropouts…some dropouts, but not substantially more than placebo.

And when you look at treatment emergent adverse events leading to treatment discontinuation, which is another thing we're obviously very interested in, it was 3% for placebo, 4.8% for 15-milligrams, so really quite close, and then somewhat higher for the 25 milligrams at 14 percent, with the most common side effects being dizziness, headache, and somnolence, which is pretty par for the course for drugs in the epilepsy space.

When you see strong results like this, coupled with strong results from the phase 2, that is often enough to go to the FDA. So, certainly, the next step, even though there is another identical study that's still ongoing. It probably makes sense and the intent is to go to the FDA with these two studies in hand you know within you know, within the next calendar year and look for approval you know relatively soon.

2026 AAN Annual Meeting: Treatment Breakthroughs from Epilepsy to Autoimmune Diseases

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