Cenobamate Shows Promise, Reduces Frequency of Partial-Onset Seizures

Marc Kamin, MD, the chief medical officer at SK Life Sciences

Marc Kamin, MD

Cenobamate, otherwise known as YKP 3089, is a small molecule neurotherapeutic azole compound is being developed by SK Biopharmaceuticals as an oral treatment for multiple conditions, including antiepileptic use in patients with partial-onset seizures.

At the American Epilepsy Society’s 72nd annual meeting, in New Orleans, Louisiana, several posters presentations were made by SK life science, the manufacturer of the investigative agent. One showed a reduction in the incidence of drug reaction with eosinophilia and systemic symptoms, while others looked at the dose at which the therapy becomes efficacious. Thus far, it has shown the ability to decrease seizure frequencies for all doses tested (100 mg/day: 35.5%, 200 mg/day: 55.0%, and 400 mg/day: 55.0%) in comparison with placebo (24.0%), according to the findings of 1 trial presented earlier this year.¹

To find out more about the therapy and what the clinical community needs to know about cenobamate, Marc Kamin, MD, the chief medical officer at SK Life Science, sat with NeurologyLive to discuss what makes it unique, as well as what these studies have discovered.

NeurologyLive: What do clinicians need to know about cenobamate?

Marc Kamin, MD: We've demonstrated that the drug works, but I think many times doctors are interested in how soon it works. We just did some very simple analyses—sort of time-to-first seizure and looking at seizure reductions earlier in the trials, and it looks like the efficacy may be beginning around 50 mg to 100 mg per day.

Again, these are sort of what they call post hoc analysis and things like that, but it's this type of information that can be very helpful to the physicians, to help them understand what to expect. Sometimes you'll say, “Well, the dose in this study was X”—200 milligrams or whatever—and people think, “Well, gee, I have to wait so long for it.” But in reality, when we did some of these analyses and we did some of these graphs and survival analyses, it looks like doctors and patients might be seeing something within the first week or two of starting this drug if you start at 50 mg. In our new study, we're starting at 12.5 mg.

Again, all this sort of adds to the body of knowledge about drug and that was the purpose of doing this that's the purpose of bringing this information out to the professionals so so I think it's it's good information and I feel that it's our responsibility to make sure that we tell the doctors and the patients everybody knows all about this drug that I can use in the best possible way. I'm committed to that and I know SK is as well, it really has a good value system which is right up there is about doing the right thing. They haven't rushed this thing. I've been the medical person on this for a long time, and they've always encouraged us to do it the right way.

What makes cenobamate unique from other therapies?

People always talk about mechanism of action as a possible issue. We do impact what's known as the persistent component of the sodium current—the sodium current is the influx of sodium into a cell that causes changes in depolarization of a cell membrane. Some drugs may affect that rapid in-rush and they affect the action potential. We seem to affect it in a different way. There's something called a persistent current, which in some epilepsy patients may be the sort of constant drip of sodium coming in, which alters the sensitivity of cells. We're able to inhibit it, so that's one piece of the puzzle. The other thing is we affect the GABA receptor, which is an inhibitory neurotransmitter. We enhance the effect of GABA at the site of the receptor.

But no one even knows yet what causes epilepsy and we don't know exactly how the drug works. Our mechanism is slightly unique, this has been seen with other drugs, but all of our channels and brains, they're all different. We hope this may be the reason, but in the end it's the patients and the physicians who are going to determine the value of this drug and how good it is. To me, the most important thing is that they know how to use it the right way. That's our responsibility, that we convey the messages and the information we have from our trials and that we educate physicians and patients as to what this drug can do so that it's used in the best possible way to get the best efficacy and to make sure it's safe.

Transcript edited for clarity.

REFERENCE

1. Krauss G, Kamin M. Efficacy and tolerability of adjunctive cenobamate therapy in different types of partial-onset seizures. Neurology. 2018;90(15 Suppl). Epub April 23, 2018. neurology.org/content/90/15_Supplement/S19.005