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
. 2021 Sep;6(3):483-492.
doi: 10.1002/epi4.12526. Epub 2021 Jul 29.

Antiepileptogenesis and disease modification: Clinical and regulatory issues

Jacqueline A French  1 , Martina Bebin  2 , Marc A Dichter  3 , Jerome Engel Jr  4 , Adam L Hartman  5 , Sergiusz Jóźwiak  6 , Pavel Klein  7 , James McNamara Sr  8 , Roy Twyman  9 , Paul Vespa  10
Affiliations

Antiepileptogenesis and disease modification: Clinical and regulatory issues

Jacqueline A French et al. Epilepsia Open. 2021 Sep.

Abstract

This is a summary report of clinical and regulatory issues discussed at the 2018 NINDS workshop, entitled "Accelerating Therapies for Antiepileptogenesis and Disease Modification." The intent of the workshop was to optimize and accelerate development of therapies for antiepileptogenesis (AEG) and disease modification in the epilepsies. The working group discussed nomenclature for antiepileptogenic therapies, subdividing them into "antiepileptogenic therapies" and "disease modifying therapies," both of which are urgently needed. We use the example of traumatic brain injury to explain issues and complexities in designing a trial for disease-preventing antiepileptogenic therapies, including identifying timing of intervention, selecting the appropriate dose, and the need for biomarkers. We discuss the recent trials of vigabatrin to prevent onset and modify epilepsy outcome in children with tuberous sclerosis (Epistop and PreVeNT). We describe a potential approach to a disease modification trial in adults, using patients with temporal lobe epilepsy. Finally, we discuss regulatory hurdles for antiepileptogenesis and disease-modifying trials.

Keywords: antiepileptogenesis; clinical trials; disease modification.

PubMed Disclaimer

Conflict of interest statement

J. French receives salary support from the Epilepsy Foundation and for consulting work and/or attending Scientific Advisory Boards on behalf of the Epilepsy Study Consortium for Adamas, Aeonian/Aeovian, Alterity Therapeutics Limited, Anavex, Arkin Holdings, Arvelle Therapeutics, Inc, Athenen Therapeutics/Carnot Pharma, Baergic Bio, Biogen, BioXcel Therapeutics, Cavion, Cerebral Therapeutics, Cerevel, Corlieve Therapeutics, Crossject, CuroNZ, Eisai, Eliem Therapeutics, Encoded Therapeutics, Engage Therapeutics, Engrail, Epalex, Epihunter, Epiminder, Equilibre BioPharmaceuticals, Fortress Biotech, Greenwich Biosciences, GW Pharma, Janssen Pharmaceutica, Knopp Biosciences, LivaNova, Longboard Pharmaceuticals, Lundbeck, Marinus, Mend Neuroscience, Merck, NeuCyte, Inc, Neumirna Therapeutics, Neurocrine, Neuropace, Otsuka Pharmaceutical Development, Ovid Therapeutics Inc, Passage Bio, Praxis, PureTech LTY Inc, Redpin, Sage, SK Life Sciences, Sofinnova, Stoke, Supernus, Synergia Medical, Takeda, UCB Inc, West Therapeutic Development, Xenon, Xeris, Zogenix, Zynerba. J. French has also received research support from the Epilepsy Study Consortium (Funded by Andrews Foundation, Eisai, Engage, Lundbeck, Pfizer, SK Life Science, Sunovion, UCB, Vogelstein Foundation) Epilepsy Study Consortium/Epilepsy Foundation (Funded by UCB), GW/FACES, and NINDS. She is on the editorial board of Lancet Neurology and Neurology Today. She is Chief Medical/Innovation Officer for the Epilepsy Foundation. She has received travel reimbursement related to research, advisory meetings, or presentation of results at scientific meetings from the Epilepsy Study Consortium, the Epilepsy Foundation, Arvelle Therapeutics, Inc, Biogen, Cerevel, Engage, Lundbeck, NeuCyte, Inc, Otsuka, Sage, UCB, Xenon, Zogenix. Sergiusz Jozwiak has received consulting, speaker, or advisory board fees from Novartis, Biogen, Eisai, and GW Pharma. Martina Bebin receives NINDS grant support and is a subinvestigator for Greenwich Biosciences. Martina Bebin is on advisory committees for Neurelis, Greenwich Biosciences, Aquestive Therapeutics, REGENXBIO. Adam Hartman is an Editorial Board member for Neurology and a consultant for Best Doctors/Teladoc, Inc Pavel Klein has received consulting, speaker, or advisory board fees from Arvelle, Aquestive, Biogen, Eisai, Engage Therapeutics, Greenwich Pharmaceuticals, Lundbeck, Neurelis, SK Life Science, Sunovion, and UCB Pharma. He receives grant support from DOD/CURE. He is a member of medical advisory board of Stratus‐Alliance, of Scientific Advisory Board of OB Pharma, and the CEO of PrevEp. Arvelle (cenobamate), Eisai (perampanel, rufinamide), GW Pharma (cannabidiol), Lundbeck (clobazam), Neurelis (Valtoco), Novartis (everolimus), SK Life Science (cenobamate), Sunovion (eslicarbazepine), and UCB Pharma (lacosamide, brivaracetam) manufacture, or sell drugs evaluated or mentioned in this study. Paul Vespa receives NINDS funding and is a consultant for Ceribell and UCB Pharmaceuticals. The remaining authors have no conflicts of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

References

    1. Ghaiyoumi A. Epilepsy [Internet]. 2019. Available from: https://www.who.int/news‐room/fact‐sheets/detail/epilepsy
    1. Begley CE, Famulari M, Annegers JF, Lairson DR, Reynolds TF, Coan S, et al The cost of epilepsy in the United States: An estimate from population‐ based clinical and survey data. Epilepsia. 2000;41(3):342–51. - PubMed
    1. Gooch CL, Pracht E, Borenstein AR. The burden of neurological disease in the United States: a summary report and call to action. Ann Neurol. 2017;81(4):479–84. - PubMed
    1. The economic burden of epilepsy in Australia, 2019‐2020. Deloitte Access Economics. 2020.
    1. Yang G, Schmiel L, Zhou M, Cintina I, Spencer D, Hogan P. Economic burden and future impact of parkinson’s disease ‐ final report [Internet]. Vol. July, Michael J. Fox Foundation ‐ The Lewin Group, Incorporated. 2019. Available from: https://www.michaeljfox.org/sites/default/files/media/document/2019Parki...

Publication types