Abstract
Although there has been an increase in the FDA approvals of CNS therapeutics over the last few years, there is still a need to understand industry practices as they relate to neurotoxicity and safety testing of therapeutics given the potential severity of the mentioned risk and divergent approaches to evaluate product-induced risks. The American College of Toxicology (ACT), the Safety Pharmacology Society (SPS) and the Society for Toxicological Pathology (STP) conducted a survey in 2024 to assess industry practices for safety testing in the nervous system.
The objective of this survey was to collect responses from participants across multiple regions across the world to understand the current landscape for safety testing in the nervous system. Respondents for the survey were based in Asia, Europe, and North America. The survey contained questions focused on the following areas: general CNS, drug abuse liability, peripheral nerve safety, and seizure liability. These questions were intended to understand practices related to the selection of in vitro and in vivo assays, animal species, as well as types of endpoints employed in nonclinical safety studies.
The survey findings indicated that a wide variety of in vitro and in vivo assays were employed to evaluate drug-induced risks (e.g., seizures, ototoxicity, abuse liability, and peripheral nerve damage) in the nervous system; and that a variety of endpoints and other design features were employed in these and other studies based on factors that included the species tested, potential pharmacological/toxicological profile of the product tested, and the clinical dose schedule supported by data from pivotal nonclinical safety studies. Findings from the survey also indicated that drug-induced risks in the nervous system were due to alterations in various factors that include species anatomy and physiology, drug on/off target effects, and experimental procedures.
Together, these findings illustrate that industry practices vary based on the numerous factors, which helps to explain the divergent approaches taken by companies to evaluate drug-related risks and the challenges related to translating animal findings across products (includes those from the same class).
About the Presenter
Marcus Delatte, PhD, is Vice President, Regulatory Strategy at Allucent. He served as a Senior Pharmacology/Toxicology Reviewer at the US FDA for 12 years. Dr. Delatte is an established expert in translating nonclinical data to inform clinical program design, including dose selection, safety monitoring, inclusion/exclusion criteria for clinical protocols, and informed consent forms. He has extensive experience in creating and implementing strategies for regulatory pathways in the US, as well as preparing and creating strategies for formal FDA meetings. His expertise and experience span multiple therapeutic areas including psychiatry, neurology, pain, rheumatology, infectious disease, immunology, cardiovascular, pulmonary, and oncology.
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