title: Thirty Years of Orphan Drug Legislation and the Development of Drugs to Treat Rare Seizure Conditions: A Cross Sectional Analysis.
abstract: BACKGROUND
  Epilepsy is a serious chronic health condition with a high morbidity impairing the life of patients and afflicted families. Many epileptic conditions, especially those affecting children, are rare disorders generating an urgent medical need for more efficacious therapy options. Therefore, we assessed the output of the US and European orphan drug legislations.
  
  
  METHODS
  Quantitative analysis of the FDA and EMA databases for orphan drug designations according to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) criteria.
  
  
  RESULTS
  Within the US Orphan Drug Act 40 designations were granted delivering nine approvals, i.e. clobazam, diazepam viscous solution for rectal administration, felbamate, fosphenytoin, lamotrigine, repository corticotropin, rufinamide, topiramate, and vigabatrin. Since 2000 the EMA granted six orphan drug designations whereof two compounds were approved, i.e. rufinamide and stiripentol. In the US, two orphan drug designations were withdrawn. Orphan drugs were approved for conditions including Lennox-Gastaut syndrome, infantile spasms, Dravet syndrome, and status epilepticus. Comparing time to approval for rufinamide, which was approved in the US and the EU to treat rare seizure conditions, the process seems faster in the EU (2.2 years) than in the US (4.3 years).
  
  
  CONCLUSIONS
  Orphan drug development in the US and in the EU delivered only few molecular entities to treat rare seizure disorders. The development programs focused on already approved antiepileptic drugs or alternative pharmaceutical formulations. Most orphan drugs approved in the US are not approved in the EU to treat rare seizures although some were introduced after 2000 when the EU adopted the Orphan Drug Regulation.
authors.affiliation: Pediatric Neurology and Metabolic Medicine, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.|Center for Rare Diseases, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
authors.forename: Jan Henje
authors.initials: JH
authors.lastname: Döring
authors.affiliation: Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.|Cooperation Unit Clinical Pharmacy, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Anette
authors.initials: A
authors.lastname: Lampert
authors.affiliation: Pediatric Neurology and Metabolic Medicine, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.|Center for Rare Diseases, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
authors.affiliation: Pediatric Neurology and Metabolic Medicine, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.|Center for Rare Diseases, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
authors.forename: Markus
authors.identifier: http://orcid.org/0000-0002-5054-5741
authors.initials: M
authors.lastname: Ries
mesh_terms: D000927:Anticonvulsants / Q000266:history / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D062313:Databases, Pharmaceutical; D017277:Drug Approval; D055808:Drug Discovery / Q000266:history / Q000331:legislation & jurisprudence*; D005060:Europe; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007880:Legislation, Drug; D009965:Orphan Drug Production / Q000266:history / Q000331:legislation & jurisprudence*; D035583:Rare Diseases / Q000188:drug therapy / Q000453:epidemiology*; D012107:Research Design; D012640:Seizures / Q000188:drug therapy / Q000453:epidemiology*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000927:Anticonvulsants