Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2025 Jul;66(7):2239-2252.
doi: 10.1111/epi.18357. Epub 2025 Mar 15.

Effectiveness and safety of adjunctive cenobamate in people with focal-onset epilepsy: Interim results after 24-week observational period from the BLESS study

Simona Lattanzi  1 , Fedele Dono  2 , Giuseppe d'Orsi  3 , Alfredo D'Aniello  4 , Mariangela Panebianco  5 , Paolo Bonanni  6 , Carlo Di Bonaventura  7 , Elisa Montalenti  8 , Antonio Gambardella  9 , Federica Ranzato  10 , Giada Pauletto  11 , Elena Tartara  12 , Angela La Neve  13 , Francesca Bisulli  14   15 , Giampaolo Vatti  16 , Patrizia Pulitano  17 , Claudio Liguori  18   19 , Giovanni Assenza  20 , Alfonso Giordano  21 , Pietro Pignatta  22 , Vincenzo Belcastro  23 , Michela Cecconi  24 , Simone Beretta  25 , Chiara Pizzanelli  26 , Marianna Pezzella  27 , Massimo Gangitano  28 , Maurizio Elia  29 , Rosaria Renna  30 , Catello Vollono  31 , Angelo Pascarella  32 , Luciana Tramacere  33 , Giovanni De Maria  34 , Daniela Audenino  35 , Maria Pia Pasolini  36 , Loretta Giuliano  37 , Rosita Galli  38 , Gionata Strigaro  39 , Monica Puligheddu  40 , Angelo Labate  41   42 , Pietro Penza  43 , Stefano Quadri  44 , David Stokelj  45 , Giovanni Boero  46 , Elisa Fallica  47 , Monica Santo Sabato  48 , Giovanni Falcicchio  49 , Nicoletta Foschi  50 , Michela Procaccini  51 , Valentina Villano  51 , Gabriele Camattari  51 , Fabiano Mele  52 , Barbara Roncari  52 , Giancarlo Di Gennaro  4 ; BLESS Study Group
Affiliations
Observational Study

Effectiveness and safety of adjunctive cenobamate in people with focal-onset epilepsy: Interim results after 24-week observational period from the BLESS study

Simona Lattanzi et al. Epilepsia. 2025 Jul.

Abstract

Objective: Cenobamate is an antiseizure medication (ASM) with a dual mechanism of action that was recently approved for the treatment of focal seizures in adults. This analysis aimed to describe the outcomes at 12 and 24 weeks after starting cenobamate therapy in a real-world setting.

Methods: BLESS [NCT05859854] is an ongoing, observational, retrospective and prospective cohort study to evaluate the real-world effectiveness and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy. Subgroup analysis was performed in subjects with 2 to 3 previous ASMs (early users) and those with >3 previous ASMs (late users).

Results: The second interim analysis of the BLESS study included 388 participants with a median (interquartile range) age of 43.0 (31.0-54.0) years. They had a median of 6.0 (4.0-9.0) prior ASMs and a median of 7.2 (3.0-20.6) monthly seizures at baseline. The median monthly seizure frequency was reduced by 59.9% (19.2%-87.3%) from baseline to 24 weeks; 229 (59.0%) subjects had a ≥50% seizure frequency reduction, and 44 (11.3%) showed sustained seizure freedom. The proportion of participants taking ≤2 concomitant ASMs increased from 217 (56.5%) at baseline to 239 (65.7%) at 24 weeks. Among the early users (n = 76, 19.6%), the median reduction in monthly seizure frequency at 24 weeks was 78.0% (50.0-97.1%), and 76.3% of subjects had a ≥50% response rate. The frequency of adverse drug reactions (ADRs) was 5.3% and 23.4% in early and late users. The most frequent ADRs were somnolence, dizziness, and balance disorder; after the occurrence of ADRs, 63.5% of participants maintained the prescribed dose, and 5.2% permanently discontinued treatment.

Significance: Cenobamate was effective in reducing seizure frequency in a real-world setting and showed a manageable safety profile. The treatment with cenobamate also reduced the burden of concomitant ASMs in both early and late users.

Keywords: cenobamate; early use; epilepsy management; real‐world evidence; seizure reduction.

PubMed Disclaimer

Conflict of interest statement

The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: Simona Lattanzi has received speaker or consultancy fees from Angelini Pharma, Eisai, GW Pharmaceuticals, Medscape, and UCB Pharma, and has served on advisory boards for Angelini Pharma, Arvelle Therapeutics, BIAL, Eisai, GW Pharmaceuticals, and Rapport Therapeutics. Fedele Dono has received speaker honoraria and travel grant from Eisai, Jazz Pharmaceuticals, and Angelini Pharma. Giuseppe d'Orsi has received speaker or consultancy fees from Angelini Pharma, Eisai, and UCB Pharma. Alfredo D'Aniello has received speaker honoraria from Angelini Pharma, UCB Pharma, and Eisai, and has participated in advisory board for Angelini Pharma. Mariangela Panebianco has received speaker or consultancy fees from Angelini Pharma, Eisai, and UCB Pharma. Paolo Bonanni has received speaker or consultancy fees from BIAL, Eisai, GW Pharmaceuticals, LivaNova, Lusofarmaco, Proveca, and Roche. Carlo Di Bonaventura has received consulting fees and honoraria from UCB Pharma, Eisai, GW Pharmaceuticals, BIAL, Angelini Pharma, Lusofarmaco, and Ecupharma. Antonio Gambardella has received speaker honoraria from Eisai, UCB Pharma, and Angelini Pharma. Federica Ranzato has received speaker fees from Angelini Pharma, Eisai, UCB Pharma, and LivaNova and has participated on an advisory board for Angelini Pharma. Giada Pauletto has received speaker's or consultancy fees from Eisai, Angelini Pharma, LivaNova, Lusofarmaco, and UCB Pharma. Elena Tartara has received speaker fees from Eisai and advisory board fees from Angelini Pharma. Angela La Neve has received speaker or consultancy fees from Eisai, Mylan, Sanofi, BIAL, GW Pharmaceuticals, UCB Pharma, Arvelle Therapeutics, Angelini Pharma, and Neuraxpharm. Francesca Bisulli has received consultancy fees from Angelini Pharma, UCB Pharma, Jazz Pharmaceuticals, and Eisai. Patrizia Pulitano, has received consulting fees or speaker honoraria from Angelini Pharma, UCB Pharma, and Eisai. Claudio Liguori has received research support and speaker honoraria from Angelini Pharma and has no other relevant conflict of interests related to this article. Vincenzo Belcastro has received consulting fees and honoraria from UCB Pharma, Angelini Pharma, Lusofarmaco, and Ecupharma. Chiara Pizzanelli has received consultancy fees from Angelini Pharma, Eisai, and UCB Pharma. Maurizio Elia has received speaker or consultancy fees from Angelini Pharma, Eisai, Lusofarmaco, Proveca, Takeda, and UCB Pharma. Rosaria Renna, has received speaker fees from Eisai. Daniela Audenino has received speaker or consultancy fees from Angelini Pharma and UCB Pharma. Loretta Giuliano has received speaker or consultancy fees from Eisai, Angelini Pharma, and Lusofarmaco. Rosita Galli has received speaker or consultancy fees from Angelini Pharma and Eisai. Gionata Strigaro has received fees from Eisai and Angelini Pharma. Monica Puligheddu has received speaker or consultancy fees from Angelini Pharma, Eisai, Lusofarmaco, Idorsia, Jazz Pharmaceuticals, Bioproject, Fidia, and UCB Pharma. Giovanni Boero has received speaker or consultancy fees from Eisai, Angelini Pharma, and UCB Pharma. Giovanni Falcicchio, has received speaker fees from Angelini Pharma. Michela Procaccini is an employee of Angelini Pharma, Italy. Valentina Villano is an employee of Angelini Pharma, Italy. Gabriele Camattari is an employee of Angelini Pharma, Italy. Fabiano Mele is an employee of IQVIA Solutions Italy SRL. Barbara Roncari is an employee of IQVIA Solutions Italy SRL. Giancarlo Di Gennaro has received speaker honoraria from Eisai, UCB Pharma, LivaNova, Lusofarmaco, and GW Pharmaceuticals; and has served on advisory boards for BIAL, Arvelle Therapeutics, Angelini Pharma, and UCB Pharma. The remaining authors have no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Median monthly seizure frequency at baseline and at 12 and 24 weeks from starting treatment with cenobamate in the overall study cohort, in subjects with 2 to 3 previous antiseizure medications (early users) and in subjects with >3 previous antiseizure medications (late users). ASMs, antiseizure medications; IQR, interquartile range.
FIGURE 2
FIGURE 2
Rates of ≥50%, ≥75%, and ≥90% reduction in monthly seizure frequency from the pre‐treatment baseline in the study cohort (A), in subjects with 2 to 3 previous antiseizure medications (early users) (B), and in subjects with >3 previous antiseizure medications (late users) (C) Percentages were computed over the total number of evaluable subjects in each subgroup. ASMs, antiseizure medications; CI, confidence interval.
FIGURE 3
FIGURE 3
Rates of 100% reduction in monthly seizure frequency from the pre‐treatment baseline during the first 24 weeks of treatment with cenobamate. Percentages were computed over the total number of evaluable subjects in each subgroup. ASMs, antiseizure medications.
See this image and copyright information in PMC

References

    1. World Health Organization . Epilepsy. 2024. https://www.who.int/en/news‐room/fact‐sheets/detail/epilepsy
    1. Sultana B, Panzini M‐A, Carpentier AV, Comtois J, Rioux B, Gore G, et al. Incidence and prevalence of drug‐resistant epilepsy: a systematic review and meta‐analysis. Neurology. 2021;96(17):805–817. - PubMed
    1. Asadi‐Pooya AA, Brigo F, Lattanzi S, Blumcke I. Adult epilepsy. Lancet. 2023;402(10399):412–424. - PubMed
    1. van Hezik‐Wester V, de Groot S, Kanters T, Versteegh M, Wagner L, Ardesch J, et al. Burden of illness in people with medically refractory epilepsy who suffer from daily to weekly seizures: 12‐month follow‐up of participants in the EPISODE study. Front Neurol. 2022;13:1012486. - PMC - PubMed
    1. Connor GS, Williamson A. Effectiveness and safety of adjunctive cenobamate for focal seizures in adults with developmental disability treated in clinical practice. Epilepsy Behav Rep. 2022;18:100533. - PMC - PubMed

Publication types

Grants and funding

LinkOut - more resources