, Volume 72, Issue 11, pp 1437–1443 | Cite as

Orphan Drugs for Rare Diseases

Is it Time to Revisit Their Special Market Access Status?
  • Steven Simoens
  • David Cassiman
  • Marc Dooms
  • Eline Picavet
Current Opinion


Orphan drugs are intended for diseases with a very low prevalence, and many countries have implemented legislation to support market access of orphan drugs. We argue that it is time to revisit the special market access status of orphan drugs. Indeed, evidence suggests that there is no societal preference for treating rare diseases. Although society appears to assign a greater value to severity of disease, this criterion is equally relevant to many common diseases. Furthermore, the criterion of equity in access to treatment, which underpins orphan drug legislation, puts more value on health improvement in rare diseases than in common diseases and implies that population health is not maximized. Finally, incentives for the development, pricing and reimbursement of orphan drugs have created market failures, including monopolistic prices and the artificial creation of rare diseases. We argue that, instead of awarding special market access status to orphan drugs, there is scope to optimize research and development (R&D) of orphan drugs and to control prices of orphan drugs by means of, for example, patent auctions, advance purchase commitments, pay-as-you-go schemes and dose-modification studies. Governments should consider carefully the right incentive strategy for R&D of orphan drugs in rare diseases.


  1. 1.
    European Commission. Regulation (EC) No 141/2000 of the European Parliament and the Council of 16 December 1999 on orphan medicinal products. Official Journal of the European Communities 2000; L 18/1 [online]. Available from URL: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2000:018:0001:0005:en:PDF [Accessed 2012 Jun 21]
  2. 2.
    United States Congress. The Orphan Drug Act. CFR Title 21 Part 316 Orphan Drugs. United States Congress 1983 [online]. Available from URL: http://law.justia.com/cfr/title21/21- [Accessed 2011 Apr 4]
  3. 3.
    Denis A, Mergaert L, Fostier C, et al. A comparative study of European rare disease and orphan drug markets. Health Pol 2010; 97: 173–9CrossRefGoogle Scholar
  4. 4.
    Rinaldi A. Adopting an orphan. EMBO Rep 2005; 6(6): 507–10PubMedCrossRefGoogle Scholar
  5. 5.
    Westermark K, Tsigkos S, Llinares J. Is it time to clarify orphan drug policies? Yes, for equity’s sake. Rapid Response 10 December 2010. BMJ 2010; 341 [online]. Available from URL: http://www.bmj.com/rapid-response/2011/11/03/it-time-clarify-orphan-drug-policies-yes-equitys-sake [Accessed 2012 Jun 22]
  6. 6.
    Picavet E, Dooms M, Cassiman D, et al. Orphan drugs for rare diseases: grounds for special status. Drug Dev Res. In pressGoogle Scholar
  7. 7.
    Tambuyzer E. Rare diseases, orphan drugs and their regulation: questions and misconceptions. Nat Rev Drug Discov 2010 Dec; 9(12): 921–9PubMedCrossRefGoogle Scholar
  8. 8.
    McCabe C, Stafinski T, Menon D. Is it time to revisit orphan drug policies?. Yes, for equity’s sake. BMJ 2010; 341: c4777PubMedCrossRefGoogle Scholar
  9. 9.
    Burls A, Austin D, Moore D. Commissioning for rare diseases: view from the frontline. BMJ 2005 Oct 29; 331(7523): 1019–21PubMedCrossRefGoogle Scholar
  10. 10.
    Desser AS, Gyrd-Hansen D, Olsen JA, et al. Societal views on orphan drugs: cross sectional survey of Norwegians aged 40 to 67. BMJ 2010; 341: c4715PubMedCrossRefGoogle Scholar
  11. 11.
    National Institute for Health and Clinical Excellence. Citizens Council Report: ultra orphan drugs. London: NICE, 2004 [online]. Available from URL: http://www.nice.org.uk/niceMedia/pdf/Citizens_Council_Ultraorphan.pdf [Accessed 2012 Mar 19]
  12. 12.
    Nord E. The trade-off between severity of illness and treatment effect in cost-value analysis of health care. Health Policy 1993 Aug; 24(3): 227–38PubMedCrossRefGoogle Scholar
  13. 13.
    Ubel PA, Loewenstein G. Distributing scarce livers: the moral reasoning of the general public. Soc Sci Med 1996 Apr; 42(7): 1049–55PubMedCrossRefGoogle Scholar
  14. 14.
    McCabe Tsuchiya A, Claxton K, et al. Orphan drugs revisited. QJM 2006 May; 99(5): 341–5CrossRefGoogle Scholar
  15. 15.
    Cookson R, McCabe C, Tsuchiya A. Public healthcare resource allocation and the rule of rescue. J Med Ethics 2008; 34(7): 540–4PubMedCrossRefGoogle Scholar
  16. 16.
    Jonsen AR. Bentham in a box: technology assessment and health care allocation. Law Med Health Care 1986; 14(3–4): 172–4PubMedGoogle Scholar
  17. 17.
    McCabe C. Balancing economic, ethical and equity concerns in orphan drugs and rare diseases. Eur J Hosp Pharm Practice 2010; 16(4): 22–4Google Scholar
  18. 18.
    Denis A, Mergaert L, Fostier C, et al. Issues surrounding orphan disease and orphan drug policies in Europe. Appl Health Econ Health Policy 2010; 8(5): 343–50PubMedCrossRefGoogle Scholar
  19. 19.
    European Organisation for Rare Diseases. Inventory of access and prices of orphan drugs across Europe: a collaborative work between national alliances on rare diseases & Eurordis [online]. Available from URL: http://img.eurordis.org/newsletter/pdf/mar-2011/ERTC_13122010_YLeCam_Final.pdf [Accessed 2012 Jun 11]
  20. 20.
    Heemstra HE. Variations in access and use of orphan drugs among EU Member States. Eur J Hosp Pharm Practice 2010; 16(4): 25–7Google Scholar
  21. 21.
    Barton JH, Emanuel EJ. The patents-based pharmaceutical development process: rationale, problems, and potential reforms. JAMA 2005 Oct 26; 294(16): 2075–82PubMedCrossRefGoogle Scholar
  22. 22.
    Simoens S. Pricing and reimbursement of orphan drugs: the need for more transparency. Orphanet J Rare Dis 2011 Jun 17; 6: 42PubMedCrossRefGoogle Scholar
  23. 23.
    Picavet E, Dooms M, Cassiman D, et al. Drugs for rare diseases: orphan designation status influences price. Appl Health Econ Health Policy 2011; 9(4): 1–5CrossRefGoogle Scholar
  24. 24.
    Hollis A. Drugs for rare diseases: paying for innovation. In: Beach C, editor. Health services restructuring in Canada: new evidence and new directions. Montreal (QC): McGill-Queen’s University Press, 2006Google Scholar
  25. 25.
    Loughnot D. Potential interactions of the Orphan Drug Act and pharmacogenomics: a flood of orphan drugs and abuses?. Am J Law Med 2005; 31(2–3): 365–80PubMedGoogle Scholar
  26. 26.
    Gatta G, van der Zwan JM, Casali PG, the RARECARE working group. Rare cancers are not so rare: the rare cancer burden in Europe. Eur J Cancer 2011; 47: 2493–511PubMedCrossRefGoogle Scholar
  27. 27.
    DiMasi JA, Grabowski HG. Economics of new oncology drug development. J Clin Oncol 2007; 25(2): 209–16PubMedCrossRefGoogle Scholar
  28. 28.
    Drummond MF, Wilson DA, Kanavos P, et al. Assessing the economic challenges posed by orphan drugs. Int J Technol Assess Health Care 2007; 23(1): 36–42PubMedCrossRefGoogle Scholar
  29. 29.
    Ferner RE, Hughes DA. The problem of orphan drugs. BMJ 2010; 341: c6456PubMedCrossRefGoogle Scholar
  30. 30.
    Grabowski HG, Vernon J. The distribution of sales revenues from pharmaceutical innovation. Pharmacoeconomics 2000; 18 Suppl. 1: 21–32PubMedCrossRefGoogle Scholar
  31. 31.
    Maeder T. The orphan drug backlash. Sci Am 2003 May; 288(5): 80–7PubMedCrossRefGoogle Scholar
  32. 32.
    Wellman-Labadie O, Zhou Y. The US Orphan Drug Act: rare disease research stimulator or commercial opportunity?. Health Policy 2009 Dec 24; 95(2–3): 216–28PubMedGoogle Scholar
  33. 33.
    Ekins S, Williams AJ, Krasowski MD, et al. In silico repositioning of approved drugs for rare and neglected diseases. Drug Discov Today 2011 Apr; 16(7–8): 298–310PubMedCrossRefGoogle Scholar
  34. 34.
    Simoens S, Picavet E, Cassiman D, et al. What price do we pay for repurposing medicines for rare diseases? BMJ 2012 Jan 4 [online]. Available from URL: http://www.bmj.com/rapid-response/2011/11/27/re-orphan-diseases-which-ones-do-we-adopt [Accessed 2012 Jun 22]
  35. 35.
    Schey C, Milanova T, Hutchings A. Estimating the budget impact of orphan medicines in Europe: 2010–2020. Orphanet J Rare Dis 2011 Sep 27; 6: 62PubMedCrossRefGoogle Scholar
  36. 36.
    Danzon PM. At what price? Nature 2007 Sep 13; 449(7159): 176–9PubMedCrossRefGoogle Scholar
  37. 37.
    Maurer SM. Choosing the right incentive strategy for research and development in neglected diseases. Bull World Health Organ 2006 May; 84(5): 376–81PubMedCrossRefGoogle Scholar
  38. 38.
    McCabe C, Edlin R, Round J. Economic considerations in the provision of treatments for rare diseases. Adv Exp Med Biol 2010; 686: 211–22PubMedCrossRefGoogle Scholar
  39. 39.
    Posada de la Paz M, Groft SC, editors. Rare diseases epidemiology. Advances in Experimental Medicine and Biology — Vol. 686. Dordrecht: Springer Science+Business Media, 2010Google Scholar
  40. 40.
    Drummond M, Evans B, LeLorier J, et al. Evidence and values: requirements for public reimbursement of drugs for rare diseases: a case study in oncology. Can J Clin Pharmacol 2009; 16(2): e273–81PubMedGoogle Scholar
  41. 41.
    Claxton KP, Sculpher MJ. Using value of information analysis to prioritise health research: some lessons from recent UK experience. Pharmacoeconomics 2006; 24(11): 1055–68PubMedCrossRefGoogle Scholar
  42. 42.
    Tunis SR, Pearson SD. Coverage options for promising technologies: Medicare’s ‘coverage with evidence development’. Health Aff (Millwood) 2006 Sep; 25(5): 1218–30CrossRefGoogle Scholar
  43. 43.
    Stafinski T, McCabe CJ, Menon D. Funding the unfundable: mechanisms for managing uncertainty in decisions on the introduction of new and innovative technologies into healthcare systems. Pharmacoeconomics 2010; 28(2): 113–42PubMedCrossRefGoogle Scholar
  44. 44.
    Owen A, Sprinks J, Meehan A, et al. A new model to evaluate the long-term cost effectiveness of orphan and highly specialised drugs following listing on the Australian Pharmaceutical Benefits Scheme: the Bosentan Patient Registry. J Med Econ 2008; 11: 235–43PubMedGoogle Scholar
  45. 45.
    Cook JP, Vernon JA, Manning R. Pharmaceutical risk-sharing agreements. Pharmacoeconomics 2008; 26(7): 551–6PubMedCrossRefGoogle Scholar
  46. 46.
    Connock M, Juarez-Garcia A, Frew E. A systematic review of the clinical effectiveness and cost-effectiveness of enzyme replacement therapies for Fabry’s disease and mucopolysaccharidosis type 1. Health Technol Assess 2006; 10(20): iii–113Google Scholar
  47. 47.
    McCabe C, Claxton K, Tsuchiya A. Orphan drugs and the NHS: should we value rarity? BMJ 2005 Oct 29; 331(7523): 1016–9PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  • Steven Simoens
    • 1
  • David Cassiman
    • 2
  • Marc Dooms
    • 3
  • Eline Picavet
    • 1
  1. 1.Research Centre for Pharmaceutical Care and Pharmaco-economicsKU LeuvenLeuvenBelgium
  2. 2.Department of HepatologyUniversity Hospitals LeuvenLeuvenBelgium
  3. 3.Hospital PharmacyUniversity Hospitals LeuvenLeuvenBelgium

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