Cenobamate’s Efficacy in Seizure Freedom and Decreasing Concomitant Medication Use


William Rosenfeld, MD, discusses the decreases his team observed in concomitant medication use with cenobamate in patients with focal seizures.

William Rosenfeld, MD, neurologist, Comprehensive Epilepsy Care Center

William Rosenfeld, MD

Data from a post hoc analysis from a phase 3 study presented at the American Epilepsy Society (AES) Annual Meeting, December 4–8, 2020, suggest that reducing doses of concomitant antiseizure medications (ASMs) led to fewer patients with focal seizures discontinuing cenobamate (Xcopri; SK Life Science).

Among the presenters was William Rosenfeld, MD, neurologist, Comprehensive Epilepsy Care Center. Rosenfeld and colleagues found that among patients who remained on cenobamate, 91 of the 401 (22.7%) concomitant baseline ASM doses were discontinued completely. Carbamazepine accounted for 28.6% of patients, oxycarbazepine for 25%, lacosamide for 21.5%, eslicarbazepine for 23.1%, clobazam for 22.6%, lamotrigine for 15.4%, and levetiracetam for 14.1%.

NeurologyLive reached out to Rosenfeld to learn more about cenobamate’s efficacy as an adjunctive therapy. He discussed how the seizure free numbers and reduction of concomitant ASMs have the potential to change the treatment landscape of focal seizures.

NeurologyLive: How can your findings impact care of patients with epileptic focal seizures?

William Rosenfeld, MD: About 25% of the baseline, anti-seizure medications were completely removed. Patients were on a total of about 400 different drugs at baseline and this was lowered to about 300 drugs. If we’re able to remove some drugs completely, that lowers side effects that comes with using multiple drugs, and costs of those drugs. Right now, cenobamate is only approved as a concomitant ASM, so we’re only able to see efficacy in adjunctive therapy in the most intractable patients. What’s interesting is that in terms of efficacy and retention, we saw that cenobamate was really the medication making the difference, and it didn’t matter what other concomitant ASMs patients were on; we still saw that efficacy. Out of the patients that stayed on cenobamate, about a third were seizure free for over 12 months, which really makes a difference in patients’ lives. I think our whole paradigm may be shifting somewhat, because of the numbers that we were seeing in terms of that seizure freedom. 

In lowering concomitant ASMs it wasn’t always lowered a lot, maybe 100–200 mg, especially if someone was on 600 mg or 700 mg, of glucose amide on the higher end. Other drugs like clobazam saw significant reductions, often we got the patients down from around 35–40 mg down to 5 mg, 10 mg, or 15 mg or, in some cases, off the drug completely. It's really about the efficacy, retention, the seizure freedom numbers and the ability to reduce medications that speaks to the success of cenobamate. The fact that it was an open-label study really helped us learn about the dose decreases, because in double blind studies, you can't lower concomitant ASMs.

What further investigations would you like to conduct into cenobamate?

We can’t do monotherapy studies yet, but we’ll definitely look into that after cenobamate is hopefully approved for monotherapy. We’re also looking at the effect of cenobamate at primary generalized tonic clonic seizures. Right now, cenobamate is approved for focal seizures in adults, but we’d also like to conduct pediatric studies. We hope to see those results in the next year. We’re looking into testing cenobamate against different concomitant ASMs individually. It definitely seems like cenobamate is the medication making the real difference no matter which concomitant ASM it’s paired with. As long as we’re seeing efficacy, we’ll lower concomitant ASMs which will only improve tolerability, lessen side effects, and make for happier patients.

Did your findings surprise you at all?

Well, we expected the efficacy, but the numbers were even better than expected. The fact that we saw such high numbers for seizure freedom surprised me. We saw 20% seizure reductions in the double blind, but then also 25% to 33% seizure freedom in this open-label study. In follow-ups of up to 12 months, we saw reductions as high as 36% to 46%.

Transcript edited for clarity. For more coverage of AES 2020, click here.

Rosenfeld W, Aboumatar S, Bhatia P, et al. Dose adjustments to concomitant antiseizure medications: post-hoc analysis of a phase 3, open-label study of cenobamate for the treatment of uncontrolled focal seizures. Presented at AES 2020 Annual Meeting; December 4–8, 2020. Abstract 336.
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