Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Cenobamate

10 evidence topics · 10 sources

Position in the second-line add-on tier

“If first-line add-on treatments tried are unsuccessful in people with focal seizures, consider 1 of the following second-line add-on treatment options:” (opens the source at this quote in a new tab)
“If the first choice is unsuccessful, consider the other second-line add-on options.” (opens the source at this quote in a new tab)

Recommendation for use in drug-resistant focal onset seizures

“Cenobamate is recommended as an option as an add-on treatment for focal onset seizures with or without secondary generalised seizures in adults with drug-resistant epilepsy that has not been adequately controlled with at least 2 antiseizure medicines.” (opens the source at this quote in a new tab)

Adjunctive cenobamate: pooled efficacy

“The overall RR for at least a 50% reduction in seizure frequency for add-on cenobamate at any dose compared to placebo was 2.17 (52% versus 24%, 95% CI 1.66 to 2.84; 2 studies, 605 participants; moderate-certainty evidence).” (opens the source at this quote in a new tab)
“The RR for seizure freedom for add-on cenobamate at any dose compared to placebo was 4.45 (16% versus 5%, 95% CI 2.25 to 8.78; 2 studies, 605 participants; moderate-certainty evidence).” (opens the source at this quote in a new tab)
“Add-on cenobamate is probably better than placebo in reducing the frequency of seizures by at least 50% and in achieving seizure freedom in adults with focal epilepsy uncontrolled by one or more concomitant ASMs (moderate level of certainty).” (opens the source at this quote in a new tab)

Adjunctive cenobamate: pivotal placebo-controlled trial

“Compared to placebo, cenobamate conferred a greater median percent seizure reduction (55.6% vs 21.5%; p < 0.0001)” (opens the source at this quote in a new tab)
“The responder rate (≥50% reduction in seizure frequency) was 50.4% for cenobamate and 22.2% for placebo (p < 0.0001).” (opens the source at this quote in a new tab)
“During maintenance, 28.3% of cenobamate-treated and 8.8% of placebo-treated patients were seizure-free.” (opens the source at this quote in a new tab)

Adjunctive cenobamate: dose-response trial

“Responder rates during the maintenance phase were 25% (26 of 102 patients) for the placebo group compared with 40% (41 of 102; odds ratio 1·97, 95% CI 1·08-3·56; p=0·0365) for the 100 mg dose group, 56% (55 of 98; 3·74, 2·06-6·80; p<0·0001) for the 200 mg dose group, and 64% (61 of 95; 5·24, 2·84-9·67; p<0·0001) for the 400 mg dose group.” (opens the source at this quote in a new tab)
“Treatment-emergent adverse events led to discontinuation in five (5%) patients in the placebo group, 11 (10%) in the 100 mg dose group, 15 (14%) in the 200 mg dose group, and 22 (20%) in the 400 mg dose group.” (opens the source at this quote in a new tab)
“One serious case of drug reaction with eosinophilia and systemic symptoms occurred in the 200 mg cenobamate group.” (opens the source at this quote in a new tab)

Adjunctive cenobamate: long-term open-label safety study

“The ≥50% responder rate for the total treatment duration was 71.7% (172/240).” (opens the source at this quote in a new tab)
“Among all patients who received a dose of cenobamate in the maintenance phase (n = 214), 13.1% (28/214) and 40.2% (86/214) achieved 100% and ≥90% seizure reduction during their entire maintenance treatment duration (median = 29.5 months).” (opens the source at this quote in a new tab)
“Common treatment-emergent adverse events among all 240 patients included fatigue (34.6%), dizziness (32.1%), and somnolence (29.6%).” (opens the source at this quote in a new tab)

Network meta-analysis of third-generation adjunctive antiseizure medications

“Sixteen trials (BRV: n = 3, CNB: n = 1, ESL: n = 4, LCM: n = 4, PER: n = 4) were included, overall enrolling 4507 patients randomised to add-on active treatments” (opens the source at this quote in a new tab)
“Cenobamate was associated with a higher rate of ≥ 50% seizure frequency reduction than BRV [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.11–3.66], ESL (OR 1.93, 95% CI 1.07–3.48), LCM (OR 1.86, 95% CI 1.04–3.32), and PER (OR 2.07, 95% CI 1.16–3.70).” (opens the source at this quote in a new tab)
“Adjunctive cenobamate had the greatest likelihood of being the best option for the ≥ 50% and 100% seizure frequency reduction. Adjunctive brivaracetam and lacosamide had the highest probabilities of being the best-tolerated treatments.” (opens the source at this quote in a new tab)

Network meta-analysis of approved add-on antiseizure medications for focal epilepsy

“All ASMs showed significantly higher ≥50% responder rate compared with placebo.” (opens the source at this quote in a new tab)
“Among treatments, significantly higher 100% responder rate was observed with cenobamate compared to eslicarbazepine (10.71; 95% CI: 1.56–323.9) and zonisamide (10.63; 95% CI: 1.37–261.2).” (opens the source at this quote in a new tab)
“Of the ASMs included, cenobamate had the greatest likelihood of allowing patients to attain seizure freedom.” (opens the source at this quote in a new tab)

Network meta-analysis ranking by seizure response and seizure freedom

“For seizure response, all ASMs were significantly superior to placebo, with RTG ranking highest, followed by CNB.” (opens the source at this quote in a new tab)
“For seizure freedom, BRV was highest-ranked, followed by CNB, with BRV 100 mg/d leading, followed by CNB 400 mg/d.” (opens the source at this quote in a new tab)

Expert consensus on position in the treatment sequence

“Cenobamate can be used after the failure of two antiseizure medications, rather than being reserved for later stages of treatment” (opens the source at this quote in a new tab)
“This manuscript aims to synthesize available clinical trial data, real-world studies, and expert opinions regarding the use of cenobamate, and to provide practical recommendations for its early introduction in patients with drug-resistant focal epilepsy, particularly following the failure of two adequately dosed ASMs.” (opens the source at this quote in a new tab)