Central Nervous System Rare Disease Drug Development

Around 3.9% of world population suffers with rare diseases, with roughly 25–30 million (almost 1 in 10) affected in the United States alone (National Institutes of Health. FAQs about rare diseases. Genetic and Rare Diseases Information Center website. https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases.Updated 30 Nov 2017; NORD 2018 Rare diseases and orphan products breakthrough summit-15Oct2018, Washington DC; GENE THERAPY: Understanding the science, assessing the evidence, and paying for value. a report from the 2016 ICER Membership Policy Summit March 2017). Unfortunately, over 90% of rare diseases lack FDA-approved therapies (National Organization of Rare Disorders. Rare disease facts. https://rarediseases.org/wp-content/uploads/2019/02/nord-rareinsights-rd-facts-2019.pdf. 2019). The designation of rare disease has implications for Orphan Drug Designation by the US Food and Drug Administration. In the United States a rare disease is defined as a disease or condition which affects 200,000 or fewer individuals or a disease or condition which affects more than 200,00 people, but the expectation of a pharmaceutical company recovering the cost of drug research and development is unreasonable. The innovative science in rare diseases is advancing at a remarkable pace: in 2019, the FDA approved 22 novel drugs and biologics with orphan disease designation in a total of 76 orphan indications. Notably, 20% of neurological products approved through 2015 have orphan indications (Abuasal B, Albusaysi S, Bhattaram VA, Uppoor R, Mehta M. Clinical drug development for rare disease in neurology (P2.194). Neurology. 2017;88(16 Supplement):P2.194). This chapter will discuss central nervous system (CNS) rare disease drug development and approvals with a focus on those approved to treat patients with rare treatment-resistant catastrophic epilepsy syndromes (e.g., Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), CDKL5 deficiency disorder), as well as treatments for spinal muscular atrophy (SMA), neurodevelopmental, and movement disorders.