Low-Dose, Slow-Titrated Cenobamate Shows No Incidence of DRESS Syndrome

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

Marc Kamin, MD

The initial results of an ongoing multicenter, open-label safety study of cenobamate have shown that a low dose of the therapy may aide the inhibition of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.¹

The research, presented at the American Epilepsy Society’s 72nd annual meeting, in New Orleans, Louisiana, has shown this effect in more than 1000 patients treated with the therapy for 6 months. The trial is evaluating the question of if going “low and slow” with cenobamate could possibly mitigate the risk for reactions such as DRESS. Patients were administered gradually increasing doses of cenobamate 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg/day at 2-week intervals. Additionally, biweekly increases of 50 mg/day to increase dosage to 400 mg/day were allowed.

To find out more about the trial, the significance of the findings, and the development of cenobamate, NeurologyLive sat down at the conference with Marc Kamin, MD, the chief medical officer at SK Life Science, the therapy's developer, to discuss these results.

NeurologyLive: What prompted this study and what were the findings?

Marc Kamin, MD: SK has been committed to developing drugs in the central nervous system for many years, probably the last 20, and they're particularly interested in epilepsy. Cenobamate was discovered by SK Biopharmaceuticals and SK Life Science, and it has been in development for the last 10 years. It's gone through a program which is pretty traditional. It has had a series of phase 1 studies. We've had 2 phase 2 efficacy studies which have confirmed the efficacy of the drug for the treatment of partial onset seizures, and during the development program what emerged was the cases of a condition known as DRESS syndrome. DRESS is an acronym for “drug reaction with eosinophilia and systemic symptoms.” It's a delayed hypersensitivity reaction that's characterized by rash and sometimes inflammation of other organs. It's serious and the company was committed to understanding it and how to best mitigate it.

There's some information in the literature about maybe slowing titration and things like that, but no one has ever really demonstrated how to really address the issue of DRESS, so we designed the study that is our initial poster here about DRESS. We enrolled over 1300 people being treated—1339 to be exact—and we started on a low dose. The clinical trials show about that 100 to 400 mg is the efficacious dose range, but we began this trial at a low dose of 12.5 mg, and we titrate up every two weeks. It's a relatively slow titration. What we demonstrated in 1339 patients was zero cases of DRESS, which was extremely encouraging.

We recently put all our information together and the company submitted an NDA in late November 2018, with this, and basically, we have these 2 efficacy studies and 1 large safety study, and we are hopeful that we will be able to bring this drug to the market to help people who are having partial seizures. That's the goal. We still have some challenges ahead of us, but we've learned a lot about this drug and all of these studies have been very helpful.

Can cenobamate help this treatment-resistant patient population down the line?

There are over 3 million people in the United States who have epilepsy, and every time they look at this data, it remains that about one-third—30% to 35%—who continue to have seizures no matter what you do. There has just been a constant unmet need in epilepsy, and that's why companies keep developing these drugs because the hope is that something will come out that may be different, may be special, but at the least will help some people. It's just been a very frustrating disease, frankly. Doctors and patients are looking for something special and different. Is cenobamate that drug? That remains to be seen.

The one thing that we have shown in abstracts and things like that is, in some of our studies, the number of patients who become seizure-free once they reach their target dose has been pretty encouraging. This has been observed by the investigators who use the drug. I've been working in this field for 25 years, and I'm hopeful that you can really make a change for many patients who have treatment-resistant partial seizures.

Transcript edited for clarity.

REFERENCE

1. Sperlin M, Klein P, Kamin M. Safety of cenobamate (YKP3089) as adjunctive treatment for uncontrolled partial seizures in a large, multi-center, open-label study. Presented at: American Epilepsy Society Annual Meeting; New Orleans, LA; December 2, 2018. aesnet.org/meetings_events/annual_meeting_abstracts/view/500991.