Identifying and Understanding Seizure Liability in Pharmaceutical Development
(Sponsored by the American College of Toxicology)
Friday, April 12, 2024 |12:00 Noon–3:45 PM EDT
Co-Chairs: Katie B. Sokolowski, PhD, DABT, Denali Therapeutics; and Brad Bolon, DVM, MS, PhD, DACVP, DABT, FATS, FIATP, FRCPath, GEMpath, Inc.
Drug-induced seizures are a major concern for central nervous system neuroactive pharmaceuticals during development. Currently, there are no guidelines for interrogating and mitigating seizure liability associated with new pharmaceuticals. Because of the risks to patient safety during clinical trials, the understanding of nonclinical characterization that informs the translation of risks to humans is an area of intense interest among drug developers and regulators. The goals of this session are to (1) understand the diverse mechanisms of seizures; (2) examine typical findings in nonclinical studies indicating seizure liability; (3) understand objectives and the elements of a screening and a pivotal nonclinical electroencephalographic (EEG) study; and (4) implement the principles of risk mitigation to de-risk seizure liability in clinical trials. To achieve these goals, we will bring together a practicing clinical neurologist with primary knowledge of patients experiencing seizures, a pharmaceutical consultant with expertise in identifying seizure liability in nonclinical studies, a director of a contract research organization with experience in designing nonclinical EEG studies, and a US FDA regulator to discuss mitigation strategies. After the session, attendees will have a better understanding of how to mitigate risks of pharmaceutical products that carry a seizures liability and understand the limitations of the current state of the art to inform research in this area.
Clinical Description and Mechanisms of Seizures
Judy S. Liu, MD, PhD, Brown University
Identifying Seizure Liability in Nonclinical Studies
Marcus Delatte, PhD, Allucent
General Design Elements of a Nonclinical EEG Study
Simon Authier, DVM, MSc, MBA, PhD, DSP, Charles River Laboratories
Risk Assessment: Management and Mitigation of Drug Products with Seizure Liability
Owen McMaster, PhD, US FDA
Active Practice 1: Identify Seizure Liability in Nonclinical Studies
Moderator: Marcus Delatte, PhD, Allucent
Active Practice 2: General Design Elements of a Nonclinical EEG Study
Moderator: Simon Authier, DVM, MSc, MBA, PhD, DSP, Charles River Laboratories
Active Practice 3: Risk Management and Mitigation of Drug Products with Seizure Liability
Moderator: Owen McMaster, PhD, US FDA