The photosensitivity model is not a model for partial (focal) seizures
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1Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA; Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Abstract:
New, more effective and less toxic medications are desperately needed for patients with partial (focal) epilepsy. Many hurdles prevent the appropriate study of promising compounds. One of these hurdles is the difficult gap between Phase I and Phase II-the expensive proof of concept to suggest that human trials in partial seizure patients will be successful. A short-cut, the photoparoxysmal response (PPR) model has recently been used to increase confidence in moving a compound into Phase II and III (K-N Trenite et al., 2015). This shortcut has substantial limitations. This article outlines these limitations in an effort to create full disclosure to all involved with development of drugs for partial seizures.
Insights
Developing new epilepsy drugs faces challenges, particularly bridging early and late-stage human trials. The photoparoxysmal response (PPR) model offers a shortcut but has significant limitations that need full disclosure for effective partial seizure medication development.
Area of Science:
- Neuroscience
- Pharmacology
- Clinical Trials
Background:
- Partial (focal) epilepsy requires novel medications with improved efficacy and safety profiles.
- Significant hurdles exist in drug development, especially the transition from Phase I to Phase II clinical trials.
- The photoparoxysmal response (PPR) model has emerged as a potential method to de-risk this transition.
Purpose of the Study:
- To critically evaluate the limitations of the photoparoxysmal response (PPR) model in preclinical drug development for partial epilepsy.
- To promote transparency regarding the PPR model's constraints in the drug development process.
- To inform researchers and developers about the challenges associated with using the PPR model as a surrogate for efficacy in partial seizure medications.
Main Methods:
- Literature review and critical analysis of the photoparoxysmal response (PPR) model's application in epilepsy drug development.
- Examination of the predictive value and limitations of the PPR model in relation to human partial seizure trials.
- Discussion of the implications of PPR model limitations for advancing compounds through clinical phases.
Main Results:
- The photoparoxysmal response (PPR) model, while offering a potential shortcut, possesses substantial limitations for predicting clinical efficacy in partial epilepsy.
- These limitations can lead to a false sense of confidence in drug candidates, impacting the progression to later-stage trials.
- A comprehensive understanding of these limitations is crucial for accurate assessment of drug potential.
Conclusions:
- The photoparoxysmal response (PPR) model should be used with caution due to its inherent limitations in predicting efficacy for partial (focal) epilepsy drugs.
- Full disclosure of these limitations is essential for all stakeholders involved in antiepileptic drug development.
- Further research and alternative models may be needed to more reliably bridge the gap between early-phase and clinical trials for partial epilepsy treatments.
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