Orphan drugs in epileptology

Background Orphan drugs are drugs specifically approved for diseases with a low prevalence. The approval processes of the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) were simplified and accelerated to improve the availability of efficacious treatment for patients with rare diseases. This review article presents the situation for orphan drug treatment of epilepsy. Objective As a systematic review, published articles and material of the regulatory authorities are used to describe approval processes, approved substances and the evidence for their efficacy, as well as health economic aspects of orphan drugs for treatment of epilepsy. Results In Europe orphan drugs have so far been approved for Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis. Randomized controlled clinical trials performed in small patient populations are available for all orphan drugs, which show a superior efficacy of antiepileptic effects compared to placebo treatment. A disease-specific mechanism of action can be assumed only for everolimus, which as an mTOR inhibitor specifically intervenes in the mechanisms of epileptogenesis in tuberous sclerosis. Discussion So far only a few antiepileptic drugs have been approved as orphan drugs. Their use leads to substantially higher costs for the healthcare system, although less than with biologicals. Syndrome-specific approval processes are critically discussed with respect to the mechanism of action of the respective substance.