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Neurol Ther
Neurol Ther
Neurology and Therapy
2193-8253
2193-6536
Springer Healthcare Cheshire

39154302
651
10.1007/s40120-024-00651-4
Review
Presurgical Use of Cenobamate for Adult and Pediatric Patients Referred for Epilepsy Surgery: Expert Panel Recommendations
Laxer Kenneth D. laxerkd@sutterhealth.org

1
Elder Christopher J. 2
Di Gennaro Giancarlo 3
Ferrari Louis 4
Krauss Gregory L. 5
Pellinen Jacob 6
Rosenfeld William E. 7
Villanueva Vicente 8
1 https://ror.org/02bjh0167 grid.17866.3e 0000 0000 9823 4542 Sutter Pacific Epilepsy Program, California Pacific Medical Center, 1100 Van Ness Ave, 6th floor, San Francisco, CA 94109 USA
2 grid.240324.3 0000 0001 2109 4251 NYU Langone Health Comprehensive Epilepsy Center, New York, NY USA
3 https://ror.org/00cpb6264 grid.419543.e 0000 0004 1760 3561 IRCCS NEUROMED, Pozzilli, IS Italy
4 https://ror.org/025t9c657 grid.430315.0 0000 0004 0415 3303 SK Life Science, Inc., Paramus, NJ USA
5 grid.21107.35 0000 0001 2171 9311 Johns Hopkins University School of Medicine, Baltimore, MD USA
6 https://ror.org/04cqn7d42 grid.499234.1 0000 0004 0433 9255 University of Colorado School of Medicine, Aurora, CO USA
7 Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, MO USA
8 https://ror.org/01ar2v535 grid.84393.35 0000 0001 0360 9602 Refractory Epilepsy Unit, Hospital Universitari I Politècnic La Fe, Valencia, Spain
18 8 2024
18 8 2024
10 2024
13 5 13371348
20 5 2024
23 7 2024
© The Author(s) 2024
2024
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Cenobamate has demonstrated efficacy in patients with treatment-resistant epilepsy, including patients who continued to have seizures after epilepsy surgery. This article provides recommendations for cenobamate use in patients referred for epilepsy surgery evaluation. A panel of six senior epileptologists from the United States and Europe with experience in presurgical evaluation of patients with epilepsy and in the use of antiseizure medications (ASMs) was convened to provide consensus recommendations for the use of cenobamate in patients referred for epilepsy surgery evaluation. Many patients referred for surgical evaluation may benefit from ASM optimization; both ASM and surgical treatment should be individualized. Based on previous clinical studies and the authors’ clinical experience with cenobamate, a substantial proportion of patients with treatment-resistant epilepsy can become seizure-free with cenobamate. We recommend a cenobamate trial and ASM optimization in parallel with presurgical evaluations. Cenobamate can be started before phase two monitoring, especially in patients who are found to be suboptimal surgery candidates. As neurostimulation therapies are generally palliative, we recommend trying cenobamate before vagus nerve stimulation (VNS), deep brain stimulation, or responsive neurostimulation (RNS). In surgically remediable cases (mesial temporal sclerosis, benign discrete lesion in non-eloquent cortex, cavernous angioma, etc.), cenobamate use should not delay imminent surgery; however, a patient may decide to defer or even cancel surgery should they achieve sustained seizure freedom with cenobamate. This decision should be made on an individual, case-by-case basis based on seizure etiology, patient preferences, potential surgical risks (mortality and morbidity), and likely surgical outcome. The addition of cenobamate after unsuccessful surgery or palliative neuromodulation may also be associated with better outcomes.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40120-024-00651-4.

Keywords

Antiseizure medications
Cenobamate
Drug-refractory epilepsy
Epilepsy surgery
Focal seizures
http://dx.doi.org/10.13039/100018439 SK Life Science issue-copyright-statement© Springer Healthcare Ltd., part of Springer Nature 2024
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pmcKey Summary Points

Why carry out this study?	
A panel of 6 senior epileptologists provided consensus recommendations on cenobamate use in patients being evaluated for epilepsy surgery.	
Patients referred for epilepsy surgery evaluation often benefit from ASM optimization, regardless of ultimate surgical candidacy.	
A trial of cenobamate is recommended in patients before epilepsy surgery in parallel with evaluations (and even before referral).	
What was learned from this study?	
Using cenobamate should not delay imminent surgery; however, if sustained seizure freedom is attained, a patient may defer or cancel surgery.	
The addition of cenobamate after surgery or neuromodulation may be associated with better outcomes in some patients.	

Introduction

Epilepsy surgery is a valuable treatment option for select patients with epilepsy [1–3]. Prompt surgical evaluation is recommended for all patients with drug-resistant epilepsy, defined by the International League Against Epilepsy as ongoing seizures despite adequate trials of at least two tolerated and appropriately selected antiseizure medications (ASMs) [3, 4]. Patients referred for surgical evaluations often benefit from the specialized epilepsy care they receive, even if they do not eventually undergo surgery [3]. For some patients, this may include improved medication management. Cenobamate is an ASM approved in the US and Canada (XCOPRI®) and in Europe (ONTOZRY®) for the treatment of adults ≥ 18 years old with focal seizures [5, 6]. In Europe, cenobamate is indicated for use after the failure of two ASMs. Cenobamate has a unique dual mechanism of action that reduces repetitive neuronal firing by preferential inhibition of the persistent Na+ current and by positive allosteric modulation of GABAA receptor-mediated tonic currents [7, 8]. High rates of treatment response, including 100% seizure reduction, were demonstrated with cenobamate in two randomized, double-blind, placebo-controlled studies of patients with uncontrolled focal seizures [9, 10], and evidence of sustained response was shown in long-term open-label clinical studies, with rates of 100% seizure reduction for any consecutive ≥ 12-month period ranging from 18.4 to 36.3% [11, 12]; see Table 1 [9–13]. Efficacy with cenobamate has been demonstrated in several patient subgroups, including patients with persistent seizures despite prior epilepsy surgery [13]. In a post hoc efficacy analysis of a phase 3 open-label study, 30.6% (26/85) of patients with uncontrolled focal seizures despite treatment with 1–3 ASMs and who had received prior epilepsy surgery achieved 100% seizure reduction for any consecutive ≥ 12-month duration when treated with adjunctive cenobamate [13]. Because data on treatment optimization with specific ASMs in patients with drug-resistant epilepsy referred for epilepsy surgery evaluation are lacking, an expert panel of international epileptologists was convened as part of an advisory board meeting to discuss their experience with cenobamate in patients referred for epilepsy surgery and to provide guidance and recommendations for the use of cenobamate in this treatment setting. The panel was brought together by SK Life Science Inc., the company that manufactures cenobamate. SK Life Science, Inc. did not have any involvement in the direction of the panel’s recommendations.Table 1 Summary of key efficacy results from pivotal cenobamate clinical studies in adults with uncontrolled focal seizures

	C013 (Chung 2020) [10]	C017 (Krauss 2020) [9]	C017 OLE (Klein 2022) [11]	C021 Post hoc efficacy analysis (Sperling 2021) [12]	C021 Post hoc efficacy analysis, surgery cohort (Abou-Khalil 2022) [13]	
Study design	Randomized, controlled study; 12-week treatment period (6-week titration, 6-week maintenance)	Randomized, controlled study; 18-week treatment period (6-week titration, 12-week maintenance)	Open-label extension of C017 study	Long-term, open-label study; 12-week titration; post hoc efficacy analysisa	Long-term, open-label study, 12-week titration; post hoc efficacy analysisa comparing efficacy in patients with ongoing seizures who had prior epilepsy surgery to patients with no prior epilepsy surgery	
Intervention	CNB 200 mg (n = 113)

Placebo (n = 109)

	CNB 100 mg (n = 108)

CNB 200 mg (n = 110)

CNB 400 mg (n = 111)

Placebo (n = 108)

	CNB (n = 355)

Target dose 300 mg (max 400 mg)

	CNB (n = 240)

Target dose: 200 mg (max 400 mg)

	CNB (n = 240)

Target dose: 200 mg (max 400 mg)

n = 85 prior epilepsy surgery; n = 155 no surgery

	
Median baseline seizure frequency per 28 daysb	CNB: 7.5

Placebo: 5.5

	CNB 100 mg: 9.5

CNB 200 mg: 11.0

CNB 400 mg: 9.0

Placebo: 8.4

	9.5	2.8	Prior surgery: 4.1

No surgery: 2.4

	
Median percent reduction in seizure frequency per 28 days vs. baseline (% of patients)	CNB 200 mg: 55.6% (p < 0.0001 vs. placebo)

Placebo: 21.5%

	CNB 100 mg: 35.5% (p = 0.0071 vs. placebo)

CNB 200 mg: 55% (p < 0.0001 vs. placebo)

CNB 400 mg 55% (p < 0.0001 vs. placebo)

Placebo: 24%

	76.1% at months 43–48	NA	NA	
 ≥ 50% reduction in seizure frequency per 28 days (% of patients)	CNB 200 mg: 50.4% (p < 0.0001 vs. placebo)

Placebo: 22.2%

	During maintenance phase:

CNB 100 mg: 40% (p = 0.0365 vs. placebo)

CNB 200 mg: 56% (p < 0.0001 vs. placebo)

CNB 400 mg: 64% (p < 0.0001 vs. placebo)

Placebo: 25%

	NA	75.7% over entire maintenance phase	NA	
100% reduction in seizure frequency per 28 days (% of patients)	During maintenance phase:

CNB 200 mg: 28.3% (p = 0.0001 vs. placebo)

Placebo: 8.8%

	During maintenance phase:

CNB 100 mg: 4% (p = 0.3688 vs. placebo)

CNB 200 mg: 11% (p = 0.0022 vs. placebo)

CNB 400 mg: 21% (p < 0.0001 vs. placebo)

Placebo: 1%

	18.4% for any ≥ 12 months	13.1% over entire maintenance phase; 36.3% for any ≥ 12 months	Prior surgery: 30.6% for any ≥ 12 months

No surgery: 39.4% for any ≥ 12 months

Resection/ablation/ disconnection surgery (with or without VNS/RNS): 35.2% for any ≥ 12 months

VNS/RNS (with or without resection/disconnection): 26.7% for any ≥ 12 months

	
Median CNB exposure	NA	NA	53.9 months	30.2 months (completers)

29.5 months (maintenance population)

	30.2 months (completers)	
CNB dose	NA	NA	median 300 mg/d	median 300 mg/d at Month 33	Prior surgery (completers):

mean 313.8 mg/d

No surgery (completers):

mean 270.5 mg/d

	
CNB cenobamate, NA not applicable, OLiE open-label extension, RNS responsive neurostimulation, VNS vagus nerve stimulation

aEligible sites from US that enrolled ≥ 11 patients who had recorded high-quality seizure data. Patients had to have ≥ 1 focal aware motor, focal impaired awareness, or focal to bilateral tonic–clonic seizure during 13 weeks baseline prior to the screening visit; focal aware motor, focal impaired awareness, or focal to bilateral tonic–clonic seizure data for evaluation (if any seizures occurred) while on treatment; raw seizure data consistently documented; and seizure data of good quality for ≥ 85% of time spent in the study

bFocal aware with motor component, focal impaired awareness, or focal to bilateral tonic–clonic seizures were assessed

Expert Panel Meeting

The expert panelists included six senior epileptologists from US and European epilepsy surgical centers (see Supplementary Material—Author Biographies). The panelists were required to have extensive real-world experience in the use of ASMs (including cenobamate), and in epilepsy-related presurgical evaluation. The panelists reported treatment of approximately 40–200 patients referred for epilepsy surgery per center. The institutions included: the Sutter Pacific Epilepsy Program (San Francisco, CA, USA), a National Association of Epilepsy Centers (NAEC) level 4 epilepsy center providing epilepsy care for northern California; the NYU Langone Comprehensive Epilepsy Center (New York, NY, USA), a NAEC level 4 epilepsy center and one of the largest epilepsy treatment programs in the US; the Scientific Institute for Research, Hospitalization, and Healthcare (IRCCS NEUROMED, Pozzilli, IS, Italy), a tertiary epilepsy center with a resective epilepsy surgery and neuromodulation [vagus nerve stimulation (VNS)] program; the Johns Hopkins Neurology and Neurosurgery Epilepsy Center (Baltimore, MD, USA), a NAEC level 4 epilepsy center providing comprehensive care from seizure diagnosis to long-term management; the University of Colorado Comprehensive Epilepsy Center (Aurora, CO, USA), a NAEC level 4 epilepsy center and the largest provider of epilepsy care in the Rocky Mountain region of the US; and the Hospital Universitari I Politècnic La Fe (Valencia, Spain), a reference center for refractory epilepsy hosted by Spain’s Ministry of Health and part of the European Reference Network EpiCARE, specializing in rare and complex epilepsies.

The objective of the 1-day virtual live meeting was to discuss the need for pharmacologic treatment optimization among patients referred to epilepsy care centers and provide agreed-upon recommendations for the use of cenobamate in patients referred for epilepsy surgery or neurostimulation evaluation. The panelists were aware of the meeting objectives and consented to participate in the meeting via email. There were two moderators who facilitated the meeting (WER and LF). Meeting logistics were provided and meeting minutes were recorded by a third party (MedVal Scientific Information Services, Princeton, NJ, USA). The consensus recommendations were derived from the live meeting, with follow-up questions via email to further refine and align the expert recommendations. All panelists agreed via email and/or verbally to participate in the development and subsequent publication of the recommendations. This article summarizes their opinions.

This work is based on previously conducted studies and the clinical expertise of the authors in treating patients with epilepsy. All participants/panelists were authors of this study. No new clinical studies were performed by the authors. No patient-specific efficacy or safety data were reported; therefore, institutional review board (IRB)/ethics approval was not required for the panel recommendations. Any previously conducted clinical studies were all IRB-approved.

Epilepsy Surgical Referral and Barriers

Early referral of patients to specialized epilepsy centers for presurgical evaluation is critically important to improving care for patients with drug-resistant epilepsy. Many patients who are referred for epilepsy surgery evaluation do not end up undergoing surgery but are still likely to benefit from the specialized diagnostic testing and treatment that they receive at specialized epilepsy care centers [3, 14]. Guidance for optimizing medical treatment is particularly important in this setting because the complexity of epilepsy cases referred for surgical evaluation has increased over time [15, 16].

Despite the potential benefits of epilepsy surgery for many patients, numerous barriers for surgery referrals still exist, which can contribute to lengthy delays from the time of diagnosis to surgery [17, 18]. The patients referred for surgical evaluation at the panelists’ institutions are generally 5 or more years post-epilepsy diagnosis (up to ~ 20 years post-diagnosis) and have a longstanding history of drug resistance (average of 3–10 previously failed ASMs). Investigations identifying and addressing the barriers to epilepsy surgery referrals are reported elsewhere [16, 19, 20], along with expert consensus recommendations for the timing of patient referrals for surgical candidacy [3].

Surgical wait times can vary depending on delays in access to care. In a study of Central and Eastern European countries, the wait time for surgery after completion of presurgical evaluations ranged from 2 weeks to 3 years [21]. Another analysis of epilepsy referral centers in Mexico and Canada found average wait times of approximately 1–2 years from referral to main investigations and surgery [18]. The time to completion of preoperative evaluations can also contribute to surgical delays [17, 22]. Despite the geographical differences between the panelists, the epilepsy presurgical evaluation protocols at all the authors’ centers were reported to be similar. The average time from referral to the panelists’ epilepsy centers to surgery was reported to be approximately 6–12 months (longer wait times up to 1.5 years may occur in the European centers if extensive presurgical studies are required). Contributing factors to surgical delays may include a lack of standardization for presurgical workup, complex imaging, ancillary testing, and coordination of expert review and interpretation of results [17]. Many patients may also be reluctant to undergo even noninvasive presurgical evaluations once they are referred to a comprehensive epilepsy surgery center [20]. According to the panelists, the main delays across their centers include the wait for video-electroencephalographic (video-EEG) long-term monitoring and for repeat monitoring if intracranial electrode recordings are required. These wait times, coupled with the wait times for ancillary evaluations [e.g., magnetoencephalography (MEG), positron-emission tomography (PET), single-photon computed tomography (SPECT), functional magnetic resonance imaging (fMRI), etc.], further delay the surgical intervention. Thus, medical therapy remains an essential treatment modality in the epilepsy surgical referral setting, and, even during presurgical screening and evaluation, it is important to continue to strive to meet treatment goals of reduction and elimination of seizures.

ASM Treatment Optimization and Cenobamate

Many patients referred to epilepsy care centers for surgical evaluation may benefit from ASM treatment optimization. Cenobamate has demonstrated efficacy in patients with treatment-resistant focal epilepsy, including patients with ongoing seizures after epilepsy surgery [13]. A summary of efficacy results from key cenobamate clinical studies is shown in Table 1 [9–13]. In the post hoc efficacy analysis of the phase 3 study, any consecutive ≥ 12 months of 100% seizure reduction with cenobamate was achieved in 35.2% (19/54) of patients who had been previously treated by resection, ablation, or disconnection surgery [with or without VNS or responsive neurostimulation (RNS)] (Table 1). In patients who had been previously treated with VNS or RNS (with or without resection/disconnection), any consecutive ≥ 12 months of 100% seizure reduction was achieved in 26.7% (12/45). Additional real-world studies have shown seizure reduction with cenobamate in highly refractory populations [23, 24]. In a large cohort of adults (n = 170) with highly drug-resistant focal seizures (median 11.3 seizures per month at baseline), of which 21% and 20% had received prior VNS and prior epilepsy surgery, respectively, 19.5% (23/118) were completely seizure-free for at least 6 months during cenobamate treatment [23].

Although the patient characteristics among the panelists’ centers vary, with some sites including patients with more severely intractable disease, the panelists’ estimated that 15–36% of their patients who initiated cenobamate while completing presurgical evaluations and awaiting surgery achieved ≥ 90% seizure reduction for at least 6 months and 5–20% achieved seizure freedom (Table 2). According to the panelists, approximately 10–30% of their patients have avoided surgery for at least 6 months with cenobamate.Table 2 Patient outcomes based on survey of panelists’ clinical experience with cenobamate

	Sutter Pacific Epilepsy Program (Laxer)	NYU Langone Comprehensive Epilepsy Center (Elder)	IRCCS NEUROMED (Di Gennaro)	Johns Hopkins University School of Medicine (Krauss)	University of Colorado School of Medicine (Pellinen)	Refractory Epilepsy Unit, Hospital Universitari I Politècnic (Villanueva)	
Number of patients tried on cenobamate	40	100	 ~ 40	210

50 surgery candidates

	50	50	
Patient characteristics	Extremely medically and surgically refractory, surgical and nonsurgical candidates	Medically and surgically refractory; focal and multifocal	Extremely refractory (despite polytherapy with 3–4 ASMs); extratemporal epilepsies; typically nonlesional	Moderate to extremely refractory; both lesional and multifocal conditions, including periventricular nodule syndrome	Drug resistant/surgical evaluation	Surgical candidates (highly refractory, with failure of at least 5 ASM)	
Estimated percentage with ≥ 90% seizure reduction for ≥ 6 months	30%	20–25%	15–20%	30%	20%	36%	
Estimated percentage with 100% seizure reduction for ≥ 6 months	5%	10+%	10–15%	20%	15–20%	16%	
Estimated percentage that avoided surgery for ≥ 6 months	10–15%	10–15%	25–30%	30% (of the 50 surgical candidates)	20%	20–25%	

Recommendations for Cenobamate Use in the Epilepsy Surgery Referral Setting

ASM treatment and epilepsy surgery should always be individualized and based on the particular needs of the patient. Since a substantial proportion of patients with treatment-resistant epilepsy can become seizure-free with cenobamate, the panelists recommend a trial of cenobamate and ASM optimization in patients while waiting for and during the presurgical evaluation (Table 3). Cenobamate should be started before phase two monitoring, especially in patients considered to have less chance of surgical success (e.g., nonlesional extratemporal epilepsies, multifocal or broad seizure patterns, epileptogenic zone in primary language/eloquent functional cortex, etc.). Based on the average dose of cenobamate (~ 330 mg/day) used by patients with ongoing focal seizures despite prior resection, ablation, or disconnection surgery in the post hoc phase 3 study, we recommend titrating the dose of cenobamate past 200 mg/day to achieve optimal efficacy in more refractory patients [13]. Because neurostimulation is generally palliative, we recommend a trial of cenobamate before VNS, deep brain stimulation, or RNS. This recommendation is based on the percentage of patients with ongoing focal seizures despite prior VNS/RNS (with or without resection or disconnection surgery) who achieved 100% seizure reduction for any consecutive ≥ 12 months with cenobamate (26.7% [12/45]) [13]. In surgically remediable cases (e.g., mesial temporal sclerosis, benign discrete lesion in non-eloquent cortex, cavernous angioma, etc.), the use of cenobamate should not delay imminent surgery; however, a patient may decide to defer or even cancel surgical treatment should they achieve sustained seizure freedom with cenobamate. Any decision to defer surgery based on the efficacy/tolerability of cenobamate should be made on an individual, case-by-case basis based on seizure etiology, patient preferences, and a discussion of the potential risks of surgery (both mortality and morbidity), and the likely outcome from the surgical option, as well as the potential risks of ongoing seizures (both mortality and morbidity) if sustained seizure freedom is not attained with an adequate trial of cenobamate. Some patients may wish to postpone surgery even if there is a less than complete reduction in seizures (e.g., ≥ 75% reduction) in order to further optimize cenobamate, whereas others may wish to proceed with surgery. A surgical treatment decision does not preclude ongoing ASM management. Many patients who are considered to be suboptimal surgical candidates following phase two monitoring may benefit from a trial of cenobamate. The use of cenobamate after surgery and/or palliative neuromodulation may be associated with better outcomes, as shown in the subgroup analyses of the phase 3 efficacy cohort [13].Table 3 Recommendations for cenobamate in the epilepsy surgery referral setting

1. Treatment (ASM or surgery) should be individualized based on the particular needs of the patient. We recommend a trial of cenobamate and ASM optimization in patients while waiting for and in parallel with presurgical evaluation	
2. Cenobamate can be started before phase two monitoring	
3. We recommend a trial of cenobamate before vagus nerve stimulation, deep brain stimulation, or responsive neurostimulation	
4. In surgically remediable cases (e.g., mesial temporal sclerosis, benign discrete lesion in non-eloquent cortex, cavernous angioma, etc.), the use of cenobamate should not delay imminent surgery; however, a patient may decide to defer or even cancel surgical treatment should they achieve sustained seizure freedom with cenobamate	
5. Any decision to defer surgery based on the efficacy/tolerability of cenobamate should be made on a case-by-case basis based on seizure etiology, patient preferences, and a discussion of the potential risks of surgery (both mortality and morbidity) and the likely outcome from the surgical option, as well as the potential risks of ongoing seizures (both mortality and morbidity) if sustained seizure freedom is not attained with an adequate trial of cenobamate

     a. Some patients may wish to postpone surgery even if there is a less than complete reduction in seizures (e.g., ≥ 75% reduction) in order to further optimize therapy, whereas others may wish to proceed with surgery

     b. Surgical treatment does not preclude the use of cenobamate. The use of cenobamate after unsuccessful surgery or palliative neuromodulation may be associated with better outcomes

	

Tolerability

Patients with refractory epilepsy referred for surgery evaluation are likely to be taking polytherapy. When adding on cenobamate, dose reductions of several concomitant ASMs, particularly those that have pharmacokinetic or pharmacodynamic interactions with cenobamate (e.g., phenytoin, phenobarbital, clobazam, and lacosamide) are recommended to minimize potential side effects, such as dizziness, somnolence, ataxia, and fatigue, and to allow for optimal dose titration of cenobamate [25–27]. Early, proactive dose adjustments during cenobamate titration are recommended for concomitant ASMs with pharmacokinetic interactions [25]. Dose adjustments for concomitant ASMs with pharmacodynamic interactions, including other sodium-channel blocking ASMs, may be made later during cenobamate titration [25]. Additional post hoc data from the phase 3 efficacy cohort showed that, despite a reduction in mean concomitant ASM drug load after starting cenobamate, efficacy was maintained, as demonstrated by the proportion of patients who maintained ≥ 50% and 100% seizure reduction rates over 24 months [28].

Conclusions

While ASM treatment and epilepsy surgery should be individualized, the two treatment modalities are not mutually exclusive; in our experience, many patients who are referred for surgery evaluation benefit from further ASM treatment optimization, both during presurgical evaluation and potentially after epilepsy surgery, particularly palliative surgery. Based on the efficacy of cenobamate in patients with treatment-resistant focal seizures, we recommend a trial of cenobamate in patients before epilepsy surgery, and in some cases even before surgical referral, given the potential delays from referral to completion of presurgical evaluations and surgery. Cenobamate may offer benefit in some patients during epilepsy surgical evaluation regardless of their ultimate surgical candidacy. It should not, however, delay the commencement of presurgical evaluation or imminent surgery in remediable cases. Some patients who achieve sustained seizure freedom on cenobamate may elect to defer or cancel surgery on a case-by-case basis with considerations including but not limited to the risk/benefit of the procedure and the advice of the specialized epilepsy care team. As clinicians continue to gain experience with cenobamate, we anticipate that, in the future, even more patients referred for epilepsy surgery evaluation may be able to avoid surgery after starting cenobamate. Further prospective research on medical treatment optimization with ASMs, such as cenobamate, as part of the management of patients with drug-resistant epilepsy, including those referred for evaluation at specialized epilepsy centers during the surgical evaluation period, will help refine and support these panel recommendations.

Supplementary Information

Below is the link to the electronic supplementary material.Supplementary file1 (PDF 97 KB)

Acknowledgements

Medical Writing, Editorial, and Other Assistance

Medical writing and editorial assistance were provided by Sarah Mizne, PharmD, and Don Fallon, ELS, of MedVal Scientific Information Services, LLC (Princeton, NJ, USA) and were funded by SK Life Science, Inc. This manuscript was prepared according to the International Society for Medical Publication Professionals’ “Good Publication Practice (GPP) Guidelines for Company-Sponsored Biomedical Research: 2022 Update.”

Author Contribution

Panelists Kenneth D. Laxer, Christopher J. Elder, Giancarlo Di Gennaro, Gregory L. Krauss, Jacob Pellinen, and Vicente Villanueva contributed to the concept and design of the project, to the literature review, and to the final recommendations. All authors, including moderators Louis Ferrari and William E. Rosenfeld, critically revised the work and gave approval for its submission.

Funding

The expert panel meeting was funded by SK Life Science, Inc. SK Life Science, Inc. also funded the journal’s Rapid Service Fee.

Data Availability

All data generated or analyzed during this study are included in this article.

Declarations

Conflict of Interest

Kenneth D. Laxer: Consultant/advisor: SK Life Science, Inc.; Speaker: SK Life Science, Inc.; Research support: SK Life Science, Inc.; Xenon. Christopher J. Elder: Speaker, SK Life Science, Inc. Giancarlo Di Gennaro: Consultant/advisor: Angelini Pharma, UCB Pharma; Speaker: Angelini Pharma, Eisai, LivaNova, Lusofarmaco, Neuraxpharm. Louis Ferrari: Employee: SK Life Science, Inc. Gregory L. Krauss: Angelini, SK Life Science, Inc.; Research support: Cerevel, Neuroelectrics, UCB Pharma. Jacob Pellinen: Consultant/advisor: SK Life Science, Inc. William E. Rosenfeld: Consultant/advisor: SK Life Science, Inc.; Speaker: SK Life Science, Inc.; Research support: SK Life Science, Inc., UCB Pharma. Vicente Villanueva: Consultant/advisor: Angelini, BIAL, Eisai, Esteve, GlaxoSmithKline, Jazz, Novartis, Sandoz, Takeda, UCB Pharma, Xenon; Speaker: Angelini, BIAL, Cevomed, Eisai, Esteve, Jazz, Newbridge, Paladin, UCB Pharma; Research support: Angelini, BIAL, Eisai, Jazz, UCB Pharma.

Ethical Approval

This work is based on previously conducted studies and the clinical expertise of the authors in treating patients with epilepsy. All participants/panelists were authors of this study. No new clinical studies were performed by the authors. No patient-specific efficacy or safety data were reported; therefore, institutional review board (IRB)/ethics approval was not required for the expert panel recommendations. Any previously conducted clinical studies were all IRB-approved.
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