Orphan drugs, orphan diseases. The first decade of orphan drug legislation in the EU

Eur J Clin Pharmacol. 2013 Apr;69(4):1009-24. doi: 10.1007/s00228-012-1423-2. Epub 2012 Oct 23.


Purpose: To assess the methodological quality of Orphan Medicinal Product (OMP) dossiers and discuss possible reasons for the small number of products licensed.

Methods: Information about orphan drug designation, approval, refusal or withdrawal was obtained from the website of the European Medicines Agency and from the European Public Assessment Reports.

Results: From 2000 up to 2010, 80.9 % of the 845 candidate orphan drug designations received a positive opinion from the European Medicines Agency (EMA)'s Committee on Orphan Medicinal Products. Of the 108 OMP marketing authorizations applied for, 63 were granted. Randomised clinical trials were done for 38 OMPs and placebo was used as comparator for nearly half the licensed drugs. One third of the OMPs were tested in trials involving fewer than 100 patients and more than half in trials with 100-200 cases. The clinical trials lasted less than one year for 42.9 % of the approved OMPs.

Conclusion: Although there may have been some small improvements over time in the methods for developing OMPs, in our opinion, the number of patients studied, the use of placebo as control, the type of outcome measure and the follow-up have often been inadequate. The present system should be changed to find better ways of fostering the development of effective and sustainable treatments for patients with orphan diseases. Public funds supporting independent clinical research on OMPs could bridge the gap between designation and approval. More stringent criteria to assess OMPs' efficacy and cost/effectiveness would improve the clinical value and the affordability of products allowed onto the market.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Clinical Trials as Topic / standards
  • Drug Approval / legislation & jurisprudence
  • Drug Approval / statistics & numerical data
  • Drug Evaluation, Preclinical / standards
  • Drugs, Investigational / economics
  • Drugs, Investigational / therapeutic use
  • Drugs, Investigational / toxicity
  • European Union
  • Evidence-Based Medicine
  • Health Policy / legislation & jurisprudence
  • Health Policy / trends
  • Humans
  • Legislation, Drug
  • Marketing
  • Orphan Drug Production / economics
  • Orphan Drug Production / legislation & jurisprudence*
  • Orphan Drug Production / statistics & numerical data
  • Outcome Assessment, Health Care
  • Rare Diseases / drug therapy*


  • Drugs, Investigational