Introduction
Epilepsy affects approximately 1 in 100 people, but many specific epilepsy syndromes are rare. For example, Lennox-Gastaut syndrome accounts for only 4% of children with epilepsy, but this triad of intractable epilepsy, developmental delay, and slow spike and wave is notoriously difficult to treat. Two new medications for Lennox-Gastaut syndrome, clobazam and rufinamide, recently received US Food and Drug Administration (FDA) approval and designation as orphan drugs under the Orphan Drug Act. Diastat®, a rectal preparation of diazepam indicated for patients taking antiepileptic drugs who have breakthrough seizures, was also approved under the Orphan Drug Act. Another orphan drug of interest to people with epilepsy is everolimus, which received FDA approval in 2009 for the treatment of subependymal giant cell astrocytomas in people with tuberous sclerosis complex, a rare genetic disorder associated with tumor growth and seizures.
Orphan Drug Act
Passed in 1983, the Orphan Drug Act facilitates the development of treatments for disorders that affect less than 200,000 people. There are approximately 7000 rare disorders that fall into this category, many of which are life-threatening. Because the relatively small number of people with these disorders represents fewer customers, potential profits are reduced compared with drugs for more common health problems such as diabetes, high blood pressure, or hyperlipidemia. To encourage the development of medications for less common disorders, the US government provides incentives such as 7 years of market exclusivity post-FDA approval, 50% tax credit for clinical development costs, grant funding, FDA guidance in protocol design, an application fee waiver, expedited review, and other assistance. Since passage of the Orphan Drug Act, more than 350 drugs have come to market under this program. The largest disease category for which orphan drugs have been approved is cancer, constituting about 30% of all orphan drug approvals.
Orphan Drug Research in Epilepsy
The investigational drug carisbamate received orphan drug designation on April 19, 2012, for infantile spasms, a severe epilepsy syndrome. Only 2500 children per year are affected by infantile spasms in the United States, but these unfortunate children may experience multiple seizure clusters per day and long-term cognitive and behavioral morbidity. Infantile spasms often lead to Lennox-Gastaut syndrome later in life. The treatment of infantile spasms remains unsatisfactory and was the topic of a recent American Academy of Neurology Guideline.
Another drug, stiripentol, used for the treatment of severe myoclonic epilepsy in infancy (Dravet syndrome), received orphan drug designation in 2008. Neither carisbamate nor stiripentol are FDA approved for the treatment of epilepsy.