XCOPRI® (cenobamate tablets) CV Efficacy

Results from a study of adult patients with a median of 9 seizures/28 days at baseline^1,2

Primary outcome: Patients taking XCOPRI experienced up to 2x greater seizure reduction compared with placebo (55% XCOPRI 400 mg, 55% XCOPRI 200 mg, 36% XCOPRI 100 mg vs 24% placebo)

Secondary outcome: As many as 1 in 5 patients experienced zero seizures with XCOPRI during the maintenance phase (21% XCOPRI 400 mg, 11% XCOPRI 200 mg, 4% XCOPRI 100 mg, 1% placebo)

Additional secondary outcome:
Median percentage reduction in 28-day seizure frequency in
partial-onset seizure subtypes (12-week maintenance phase)^1,3

*Partial-onset=focal; simple partial=focal aware; complex partial=focal unaware; secondary generalized tonic-clonic=focal to bilateral tonic-clonic.⁴

^†Only patients with simple partial motor seizures were included in the study.

XCOPRI was studied across 2 multicenter, randomized, double-blind, placebo-controlled trials in adult patients with partial-onset seizures with or without secondary generalization.²

1-3

concomitant ASMs were not adequately controlling patients at baseline^2‡

PLACEBO

Patients in the placebo arm remained on their current ASM^1,5

of patients were taking 2 or more concomitant ASMs²

24YEARS

was the approximate duration of epilepsy for patients in both studies²

~9SEIZURES

per 28 days was the median baseline seizure frequency for patients in both studies²

^‡The more frequently used ASMs were levetiracetam, lamotrigine, valproate or valproic acid, carbamazepine, oxcarbazepine, clobazam, lacosamide, and topiramate.^1,5

ASMs=anti-seizure medications.

The efficacy of XCOPRI as adjunctive therapy in partial-onset seizures was established in 2 multicenter, randomized, double-blind, placebo-controlled studies in adult patients (Study 1 and Study 2). Patients had partial-onset seizures with or without secondary generalization and were not adequately controlled with 1 to 3 concomitant ASMs. Study 1 (N=221) compared XCOPRI 200 mg/day with placebo. Study 2 (N=434) compared XCOPRI 100 mg/day, 200 mg/day, and 400 mg/day with placebo. The double-blind treatment period consisted of a titration phase (6 weeks) and a maintenance phase (6 weeks for Study 1 and 12 weeks for Study 2). In both studies, patients were started on a higher daily dosage and/or faster titration than the Prescribing Information recommendation. The primary outcome was median percentage reduction in 28-day seizure frequency during the double-blind treatment period.

In Study 1, patients were started on a daily dosage of 50 mg (a higher starting dosage than currently recommended) and subsequently increased by 50 mg/day every 2 weeks, until the final daily target dosage of 200 mg/day was achieved. In Study 2, patients were started on a daily dosage of 50 mg (a higher starting dosage than currently recommended) and subsequently increased by 50 mg/day every week (a faster titration than currently recommended) until 100 mg/day or 200 mg/day was reached; daily dosage was then increased by 100 mg/day every week in patients randomized to 400 mg/day.

Results from a post hoc analysis of a phase 3 study: Percentage of patients with 1-2 seizures/28 days
at baseline who achieved zero seizures within the first 4 weeks taking XCOPRI

Limitations: This post hoc analysis of an open-label phase 3 study of XCOPRI did not include a control arm. These data are descriptive and representative of an enriched population with a relatively small number of patients. Appropriate multiplicity adjustments were not applied.

XCOPRI was assessed in a multicenter, open-label safety study in patients 18 to 70 years old with uncontrolled focal seizures despite taking a stable dosage of 1 to 3 anti-seizure medications. The study included a screening period of up to 21 days followed by an open-label treatment period consisting of a 12-week titration phase, followed by an open-label maintenance phase. The maintenance phase continued for the length of the study (total study duration was up to 43 months). Patients initiated XCOPRI treatment using the FDA-approved titration schedule. After reaching 200 mg/day, further increases up to 400 mg/day using biweekly increments of 50 mg/day were allowed during the maintenance phase. Reductions below 200 mg were allowed at investigators’ clinical judgment (minimum allowed dosage was 50 mg/day). XCOPRI monotherapy was not allowed. Patient visits occurred every 2 weeks for 16 weeks and then every 1 to 3 months.

A post hoc analysis in a subset of patients (n=240) evaluated the impact of baseline seizure frequency (<3 seizures/28 days vs ≥3 seizures/28 days) on mean XCOPRI dosage required to achieve 100% seizure reduction, duration of this response, and responder rates. To be eligible for the post hoc analysis, the following criteria must have been met: patients must have had at least 1 focal aware motor, focal impaired awareness, or focal to bilateral tonic-clonic seizure per 13 weeks baseline prior to screening visit; seizure data while on treatment; and consistent documentation of good-quality, raw seizure data for ≥85% of the time spent in the study. Responder rates (≥50%, ≥75%, ≥90%, and 100%) were assessed during the entire treatment period (ie, including during the titration and maintenance phases).

Results from a post hoc analysis of a phase 3 study:

Zero seizures achieved with XCOPRI regardless of baseline seizure frequency

*Among patients continuing cenobamate at data cut-off.

Actor portrayals.

Results from a post hoc analysis of a phase 3 study:

of patients on XCOPRI discontinued and/or replaced

1 or more anti-seizure medications (ASMs)

across all drug classes (110/177)⁷

In this group of patients there was no increase or addition of concomitant ASMs.⁷*

The most common concomitant ASMs used at baseline included lacosamide, levetiracetam, lamotrigine, zonisamide, and clobazam.⁸

GUIDANCE FOR SWITCHING ON XCOPRI

*Sodium channel blockers, synaptic vesicle protein 2A ligands, benzodiazepines, and others.

“XCOPRI is not just for your hard-to-treat patients. XCOPRI may help many of your patients, even those experiencing few seizures or those who were recently diagnosed.”

– David Vossler, MD, FAAN, FAES, FACNS

Watch expert video

10+ years of clinical trial and real-world experience

Well-studied safety, with over 220,000 patients treated worldwide* and long-term retention rates

Review safety profile

Access

XCOPRI is widely accessible with low copays. Discover support available to get started

Learn about access

*Worldwide new-to-brand cenobamate prescriptions as of June 2025. Source: IQVIA.

References: 1. Krauss GL, Klein P, Brandt C, et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trial. Lancet Neurol. 2020;19(1):38-48. 2. XCOPRI [package insert]. Paramus, NJ: SK Life Science, Inc. 3. Krauss GL, Klein P, Brandt C, et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trial. Lancet Neurol. 2020;19(1)(suppl 1):S1-S7. 4. Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):522-530. 5. Chung SS, French JA, Kowalski J, et al. Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures. Neurology. 2020;94(22):e2311-e2322. 6. Aboumatar S, Biton V, Wechsler R, Ferrari L, Rosenfeld WE. Post hoc analysis of a phase 3 study for treatment of uncontrolled focal seizures: adjunctive cenobamate dose and seizure reduction by baseline seizure frequency. Epilepsy Res. 2022;186:107014. 7. Data on file. SK Life Science, Inc. 8. Rosenfeld WE, Abou-Khalil B, Aboumatar S, et al. Post hoc analysis of a phase 3, multicenter, open-label study of cenobamate for treatment of uncontrolled focal seizures: effects of dose adjustments of concomitant antiseizure medications. Epilepsia. 2021;62(12):3016-3028.

INDICATION

XCOPRI is indicated for the
treatment of partial-onset
seizures in adult patients.

Important Safety Information
and indication

CONTRAINDICATIONS
XCOPRI is contraindicated in patients with hypersensitivity to cenobamate or any of the ingredients in the product.
XCOPRI is contraindicated in patients with Familial Short QT syndrome.

IMPORTANT SAFETY INFORMATION and INDICATION for XCOPRI^® (cenobamate tablets) CV

CONTRAINDICATIONS

XCOPRI is contraindicated in patients with hypersensitivity to cenobamate or any of the ingredients in the product.

XCOPRI is contraindicated in patients with Familial Short QT syndrome.

WARNINGS AND PRECAUTIONS

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Also known as Multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including XCOPRI. DRESS has been reported, including one fatality, when XCOPRI is titrated rapidly (weekly or faster titration). No cases of DRESS were reported in an open-label safety study of 1339 partial-onset seizure patients when XCOPRI was initiated at 12.5 mg/day and titrated every two weeks. This finding does not establish that the risk of DRESS is prevented by a slower titration; however, XCOPRI should be initiated at 12.5 mg once daily and titrated every two weeks. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement. Eosinophilia is often present. If such signs or symptoms are present, the patient should be evaluated immediately. XCOPRI should be discontinued immediately and not restarted if an alternative etiology for the signs or symptoms cannot be established.

QT Shortening: XCOPRI can cause shortening of the QT interval. Caution should be used when administering XCOPRI and other drugs that shorten the QT interval as there may be a synergistic effect on the QT interval that would increase the QT shortening risk.

Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including XCOPRI, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Advise patients, their caregivers, and/or families to be alert for these behavioral changes and report them immediately to a healthcare provider.

Liver Injury: Clinically significant liver injury has occurred in patients taking XCOPRI. Obtain serum transaminases (ALT and AST) and total bilirubin, if not recently available (i.e., within 3 months) before initiating XCOPRI, and during treatment if clinically indicated. Monitor patients for signs and symptoms of any hepatic injury during treatment. Discontinue XCOPRI in patients with evidence of liver injury in the absence of an alternative etiology.

Neurological Adverse Reactions: XCOPRI can cause dose-dependent increases in the neurologic adverse reactions including dizziness, diplopia, disturbance in gait and coordination, somnolence, and fatigue.

Prescribers should advise patients against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery, until the effect of XCOPRI is known.

Withdrawal of AEDs: As with all antiepileptic drugs, XCOPRI should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. If withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.

MOST COMMON ADVERSE REACTIONS

In adult adjunctive therapy placebo-controlled clinical studies, the most common adverse reactions that occurred in XCOPRI-treated patients (incidence at least 10% and greater than placebo) were somnolence, dizziness, fatigue, diplopia, headache.

DOSING CONSIDERATIONS

Dosage adjustment of XCOPRI or other concomitant medications may be necessary.

Consider gradually reducing phenytoin dosages by up to 50% during initial titration.
Consider reducing dosages of phenobarbital and clobazam as needed when used concomitantly with XCOPRI.
When XCOPRI and carbamazepine or lamotrigine are taken concomitantly, consider increasing dosages as needed of carbamazepine or lamotrigine.
Consider increasing dosages as needed of drugs which are CYP2B6 and CYP3A substrates and decreasing dosages as needed of drugs which are CYP2C19 substrates.
Effectiveness of hormonal oral contraceptives may be reduced when administered concomitantly with XCOPRI. Women should use additional or alternative non-hormonal birth control.

Dosage reduction of XCOPRI may be considered in patients with mild to moderate and severe renal impairment. XCOPRI is not recommended in end-stage renal disease.

The maximum recommended daily dose is 200 mg for patients with mild or moderate hepatic impairment. XCOPRI is not recommended in patients with severe hepatic impairment.

DRUG ABUSE

XCOPRI is a Schedule V controlled substance.

INDICATION

XCOPRI is indicated for the treatment of partial-onset seizures in adult patients.

Please see full Prescribing Information.

INDICATION

Important Safety Information and indication

Important Safety Information
and indication