Issues for new antiepilepsy drug development

Abstract

Purpose of review: Preclinical research in epileptology has been very successful in producing effective drugs. Unfortunately, however, seizures are still not adequately controlled in a third of the affected individuals, and comorbidities still impose a major burden on the quality of life. New preclinical and clinical drug development strategies are needed to identify drugs that target these unmet medical needs.

Recent findings: Even in recent years, the antiseizure approach based on screenings has contributed to the identification of new drugs. Thus, it should not be abandoned. However, we propose that a radically new approach, specifically designed to tackle the existing gaps in care, should be developed to complement the traditional screening. This new approach will require integrated strategies for preclinical screening and experimental trial design. In this review, we will attempt to address some of the issues that must be resolved to engage this effort. Are there suitable models to tackle the unmet therapeutic needs in epilepsy? Are there ways to de-risk the transition from preclinical to clinical studies? Are there ways to improve the efficiency of clinical trials and to design ad hoc trials for the unmet therapeutic needs?

Summary: Development and validation of a new, integrated strategy for antiepilepsy drug development is needed to identify truly innovative drugs.

Figure 1

Typical placebo-controlled add-on trial of new anti-seizure drugs in treatment-resistant focal epilepsy.