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
. 2024 Aug;13(4):1203-1217.
doi: 10.1007/s40120-024-00634-5. Epub 2024 Jun 8.

Effectiveness and Safety of Adjunctive Cenobamate in People with Focal-Onset Epilepsy: Evidence from the First Interim Analysis of the BLESS Study

Simona Lattanzi  1 , Federica Ranzato  2 , Carlo Di Bonaventura  3 , Paolo Bonanni  4 , Antonio Gambardella  5 , Elena Tartara  6 , Giovanni Assenza  7 , Michela Procaccini  8 , Nathalie Falsetto  8 , Valentina Villano  8 , Gabriele Camattari  8 , Alessandra Ori  9 , Giancarlo Di Gennaro  10 ; BLESS Study Group
Collaborators, Affiliations

Effectiveness and Safety of Adjunctive Cenobamate in People with Focal-Onset Epilepsy: Evidence from the First Interim Analysis of the BLESS Study

Simona Lattanzi et al. Neurol Ther. 2024 Aug.

Abstract

Introduction: Despite new anti-seizure medications (ASMs) being introduced into clinical practice, about one-third of people with epilepsy do not reach seizure control. Cenobamate is a novel tetrazole-derived carbamate compound with a dual mechanism of action. In randomized controlled trials, adjunctive cenobamate reduced the frequency of focal seizures in people with uncontrolled epilepsy. Studies performed in real-world settings are useful to complement this evidence and better characterize the drug profile.

Methods: The Italian BLESS ("Cenobamate in Adults With Focal-Onset Seizures") study is an observational cohort study aimed to evaluate the effectiveness, tolerability, and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy in the context of real-world clinical practice. The study is ongoing and conducted at 50 centers in Italy. This first interim analysis includes participants enrolled until June 2023 and with 12-week outcome data available.

Results: Forty participants with a median age of 36.5 (interquartile range [IQR] 26.0-47.5) years were included. The median monthly seizure frequency at baseline was 6.0 (IQR 2.5-17.3) seizures and 31 (77.5%) participants had failed four or more ASMs before cenobamate. At 12 weeks from starting cenobamate, the median reduction in monthly seizure frequency was 52.8% (IQR 27.1-80.3%); 22 (55.0%) participants had a ≥ 50% reduction in baseline seizure frequency and six (15.0%) reached seizure freedom. The median number of concomitant ASMs decreased from 3 (IQR 2-3) at baseline to 2 (IQR 2-3) at 12 weeks and the proportion of patients treated with > 2 concomitant ASMs decreased from 52.5% to 40.0%. Seven (17.5%) patients reported a total of 12 adverse events, 11 of which were considered adverse drug reactions to cenobamate.

Conclusion: In adults with uncontrolled focal seizures, the treatment with adjunctive cenobamate was well tolerated and was associated with improved seizure control and a reduction of the burden of concomitant ASMs.

Trial registration number: NCT05859854 (ClinicalTrials.gov Identifier).

Keywords: Antiepileptic; Cenobamate; Effectiveness; Epilepsy; Focal seizure; Italian clinical practice; Observational; Real-world evidence; Safety.

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. Federica Ranzato has received speaker fees from Angelini Pharma, Eisai, UCB, and LivaNova and has participated in advisory board for Angelini Pharma. Carlo Di Bonaventura has received consulting fees and honoraria from UCB Pharma, Eisai, GW Pharmaceuticals, Bial, Angelini Pharma, Lusofarmaco, and Ecupharma. Paolo Bonanni has received speaker’s or consultancy fees from EISAI, Angelini, Jazz and Livanova and has served on advisory boards for BIAL, Eisai, Proveca outside the submitted work. Antonio Gambardella and Giovanni Assenza declare no conflict of interest. Elena Tartara has received speaker fees from Eisai and advisory board fees from Angelini. Michela Procaccini is an employee of Angelini Pharma, Italy. Nathalie Falsetto 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. Alessandra Ori is an employee of IQVIA-Medineos. Giancarlo Di Gennaro has received speaker honoraria from EISAI, UCB-Pharma, Livanova, Lusofarmaco, GW Pharmaceuticals. Served on advisory boards for Bial, Arvelle Therapeutics, Angelini Pharma, UCB-Pharma.

Figures

Fig. 1
Fig. 1
Monthly seizure frequency at pre-treatment baseline and at 12 weeks. The median (IQR) pre-treatment baseline number of monthly seizures was 6.0 (2.5–17.3) seizures versus 3.8 (1.2–7.6) at 12 weeks. IQR interquartile range
Fig. 2
Fig. 2
Rates of ≥ 50%, ≥ 75%, ≥ 90%, and 100% reduction in monthly seizure frequency from the pre-treatment baseline to 12 weeks. Percentages were computed over the total number of participants with available intra-patient percent change in monthly seizure frequency at the time point of interest versus pre-treatment baseline monthly seizure frequency (N = 40). PwE people with epilepsy, CI confidence interval
See this image and copyright information in PMC

References

    1. Ioannou P, Foster DL, Sander JW, et al. The burden of epilepsy and unmet need in people with focal seizures. Brain Behav. 2022;12(9): e2589. 10.1002/brb3.2589 - DOI - PMC - PubMed
    1. Elizebath R, Zhang E, Coe P, Gutierrez EG, Yang J, Krauss GL, Epilepsy Behav. Cenobamate treatment of focal-onset seizures: Quality of life and outcome during up to eight years of treatment. 2021;116:107796 - PubMed
    1. Asadi-Pooya AA, Brigo F, Lattanzi S, Blumcke I. Adult epilepsy. Lancet. 2023;402:412–24. 10.1016/S0140-6736(23)01048-6 - DOI - PubMed
    1. Chen Z, Brodie MJ, Liew D, Kwan P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 2018;75:279–86. 10.1001/jamaneurol.2017.3949 - DOI - PMC - PubMed
    1. ONTOZRY® Summary of Product Characteristics_last update on January 2024

Associated data

LinkOut - more resources