Skip to main content
Log in

Availability of and Access to Orphan Drugs

An International Comparison of Pharmaceutical Treatments for Pulmonary Arterial Hypertension, Fabry Disease, Hereditary Angioedema and Chronic Myeloid Leukaemia

  • Original Research Article
  • Availability of and Access to Orphan Drugs
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Abstract

Background: Market authorization does not guarantee patient access to any given drug. This is particularly true for costly orphan drugs because access depends primarily on co-payments, reimbursement policies and prices. The objective of this article is to identify differences in the availability of orphan drugs and in patient access to them in 11 pharmaceutical markets: Australia, Canada, England, France, Germany, Hungary, the Netherlands, Poland, Slovakia, Switzerland and the US.

Methods: Four rare diseases were selected for analysis: pulmonary arterial hypertension (PAH), Fabry disease (FD), hereditary angioedema (HAE) and chronic myeloid leukaemia (CML). Indicators for availability were defined as (i) the indications for which orphan drugs had been authorized in the treatment of these diseases; (ii) the application date; and (iii) the date upon which these drugs received market authorization in each country. Indicators of patient access were defined as (i) the outcomes of technology appraisals; (ii) the extent of coverage provided by healthcare payers; and (iii) the price of the drugs in each country. For PAH we analysed bosentan, iloprost, sildenafil, treprostinil (intravenous and inhaled) as well as sitaxentan and ambrisentan; for FD we analysed agalsidase alfa and agalsidase beta; for HAE we analysed icatibant, ecallantide and two complement C1s inhibitors; for CML we analysed imatinib, dasatinib and nilotinib.

Results: Most drugs included in this study had received market authorization in all countries, but the range of indications for which they had been authorized differed by country. The broadest range of indications was found in Australia, and the largest variations in indications were found for PAH drugs. Authorization process speed (the time between application and market authorization) was fastest in the US, with an average of 362 days, followed by the EU (394 days). The highest prices for the included drugs were found in Germany and the US, and the lowest in Canada, Australia and England. Although the prices of all of the included drugs were high compared with those of most non-orphan drugs, most of the insurance plans in our country sample provided coverage for authorized drugs after a certain threshold.

Conclusions: Availability of and access to orphan drugs play a key role in determining whether patients will receive adequate and efficient treatment. Although the present study showed some variations between countries in selected indicators of availability and access to orphan drugs, virtually all of the drugs in question were available and accessible in our sample. However, substantial co-payments in the US and Canada represent important barriers to patient access, especially in the case of expensive treatments such as those analysed in this study.

Market exclusivity is a strong instrument for fostering orphan drug development and drug availability. However, despite the positive effect of this instrument, the conditions under which market exclusivity is granted should be reconsidered in cases where the costs of developing an orphan drug have already been amortized through the use of the drug’s active ingredient for the treatment of a common indication.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Table II
Table III
Table IV
Table V

Similar content being viewed by others

References

  1. US FDA. Developing orphan products: FDA and Rare Disease Day [FDA Consumer Health Information; online]. Available from URL: http://www.fda.gov/downloads/ForConsumers/ConsumerUpdates/ucm107301.pdf [Accessed 2009 Aug 19]

    Google Scholar 

  2. Haffner ME. Adopting orphan drugs: two dozen years of treating rare diseases. N Engl J Med 2006 Feb 2; 354 (5): 445–7

    Article  CAS  PubMed  Google Scholar 

  3. US Department of Health and Human Services. US FDA. Orphan drug product designation database. 2009 [online]. Available from URL: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm [Accessed 2010 Sep 3]

    Google Scholar 

  4. 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): 36–42

    Article  PubMed  Google Scholar 

  5. Dear JW, Lilitkarntakul P, Webb DJ. Are rare diseases still orphans or happily adopted? The challenges of developing and using orphan medicinal products. Br J Clin Pharmacol 2006 Sep; 62 (3): 264–71

    Google Scholar 

  6. Joppi R, Bertele V, Garattini S. Orphan drug development is progressing too slowly. Br J Clin Pharmacol 2006 Mar; 61 (3): 355–60

    Article  CAS  PubMed  Google Scholar 

  7. Enzmann H, Lutz J. European incentives for orphan medicinal products. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2008 May; 51 (5): 500–8

    Article  CAS  PubMed  Google Scholar 

  8. Heemstra HE, de Vrueh RL, van Weely S, et al. Predictors of orphan drug approval in the European Union. Eur J Clin Pharmacol 2008 May; 64 (5): 545–52

    Article  PubMed  Google Scholar 

  9. Joppi R, Bertele V, Garattini S. Orphan drug development is not taking off. Br J Clin Pharmacol 2009 May; 67 (5): 494–502

    Article  CAS  PubMed  Google Scholar 

  10. Asbury CH. The Orphan Drug Act: the first 7 years. JAMA 1991 Feb 20; 265 (7): 893–7

    Article  CAS  PubMed  Google Scholar 

  11. Seoane-Vazquez E, Rodriguez-Monguio R, Szeinbach SL, et al. Incentives for orphan drug research and development in the United States. Orphanet J Rare Dis 2008; 3: 33

    Article  PubMed  Google Scholar 

  12. Yin W. Market incentives and pharmaceutical innovation. J Health Econ 2008 Jul; 27 (4): 1060–77

    Article  PubMed  Google Scholar 

  13. Griggs RC, Batshaw M, Dunkle M, et al. Clinical research for rare disease: opportunities, challenges, and solutions. Mol Genet Metab 2009 Jan; 96 (1): 20–6

    Article  CAS  PubMed  Google Scholar 

  14. DiMasi JA, Grabowski HG. Economics of new oncology drug development. J Clin Oncol 2007 Jan 10; 25 (2): 209–16

    Article  PubMed  Google Scholar 

  15. Rinaldi A. Adopting an orphan. EMBO Rep 2005 Jun; 6 (6): 507–10

    Article  CAS  PubMed  Google Scholar 

  16. Thamer M, Brennan N, Semansky R. A cross-national comparison of orphan drug policies: implications for the US Orphan Drug Act. J Health Polit Policy Law 1998 Apr; 23 (2): 265–90

    CAS  PubMed  Google Scholar 

  17. Beck M. Agalsidase alfa for the treatment of Fabry disease: new data on clinical efficacy and safety. Expert Opin Biol Ther 2009 Feb; 9 (2): 255–61

    Article  CAS  PubMed  Google Scholar 

  18. Barst RJ, Gibbs JS, Ghofrani HA, et al. Updated evidencebased treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol 2009 Jun 30; 54 (1 Suppl.): S78–84

    Article  CAS  Google Scholar 

  19. Hochhaus A, O’Brien SG, Guilhot F, et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 2009 Jun; 23 (6): 1054–61

    Article  CAS  PubMed  Google Scholar 

  20. Cohen J, Cairns C, Paquette C, et al. Comparing patient access to pharmaceuticals in the UK and US. Appl Health Econ Health Policy 2006; 5 (3): 177–87

    Article  PubMed  Google Scholar 

  21. Cohen J, Faden L, Predaris S, et al. Patient access to pharmaceuticals: an international comparison. Eur J Health Econ 2007 Sep; 8 (3): 53–66

    Article  Google Scholar 

  22. Garattini L, Cornago D, De Compadri P. Pricing and reimbursement of in-patent drugs in seven European countries: a comparative analysis. Health Policy 2007 Aug; 82 (3): 330–9

    Article  PubMed  Google Scholar 

  23. Peacock AJ. Treatment of pulmonary hypertension. BMJ 2003 Apr 19; 326 (7394): 835–6

    Article  PubMed  Google Scholar 

  24. Barst RJ, McGoon M, Torbicki A, et al. Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2004 Jun 16; 43 (12 Suppl. S): 40S–7S

    Article  PubMed  Google Scholar 

  25. Simonneau G, Galie N, Rubin LJ, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004 Jun 16; 43 (12 Suppl. S): 5S–12S

    Article  PubMed  Google Scholar 

  26. Grau AJ, Schwaninger M, Goebel HH, et al. Fabry’s disease: new therapeutic options for this lysosomal storage disorder. Nervenarzt 2003 Jun; 74 (6): 489–96

    CAS  PubMed  Google Scholar 

  27. Reid B. New products highlight ambiguity of orphan drug law. Nat Biotechnol 2003 Jan; 21 (1): 6–7

    Article  CAS  PubMed  Google Scholar 

  28. Vedder AC, Linthorst GE, Houge G, et al. Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg. PLoS One 2007; 2 (7): e598

    Article  Google Scholar 

  29. Eng CM, Banikazemi M, Gordon RE, et al. A phase 1/2 clinical trial of enzyme replacement in Fabry disease: pharmacokinetic, substrate clearance, and safety studies. Am J Hum Genet 2001 Mar; 68 (3): 711–22

    Article  CAS  PubMed  Google Scholar 

  30. Schiffmann R, Kopp JB, Austin 3rd HA, et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 2001 Jun 6; 285 (21): 2743–9

    Article  CAS  PubMed  Google Scholar 

  31. Zuraw BL. Clinical practice: hereditary angioedema. N Engl J Med 2008 Sep 4; 359 (10): 1027–36

    Article  CAS  PubMed  Google Scholar 

  32. Frank MM. 8. Hereditary angioedema. J Allergy Clin Immunol 2008 Feb; 121 (2 Suppl.): S398–401; quiz S419

    Article  CAS  Google Scholar 

  33. Orphanet. Prevalence of rare diseases: bibliographic data. Orphanet Report Series. Orphanet, 2009 [online]. Available from URL: http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf [Accessed 2009 Aug 12]

  34. Hochhaus A, Berger U, Hehlmann R. Chronische myeloische Leukämie. Empfehlungen zur Diagnostik und Therapie 2. Auflage ed. Bremen: Uni-Med, 2004

    Google Scholar 

  35. Peggs K, Mackinnon S. Imatinib mesylate: the new gold standard for treatment of chronic myeloid leukemia. N Engl J Med 2003 Mar 13; 348 (11): 1048–50

    Article  PubMed  Google Scholar 

  36. OANDA. Historical exchange rates [online]. Available from URL: http://www.oanda.com/currency/historical-rates [Accessed 2009 Nov 18]

    Google Scholar 

  37. Organisation for Economic Co-operation and Development. PPPs and exchange rates [online]. Available from URL: http://stats.oecd.org/Index.aspx?DataSetCode=SNA_TABLE4 [Accessed 2009 Sep 9]

    Google Scholar 

  38. Levy JH, Freiberger DJ, Roback J. Hereditary angioedema: current and emerging treatment options. Anesth Analg 2010 May; 110 (5): 1271–80

    Article  CAS  PubMed  Google Scholar 

  39. US FDA. Full prescribing information: Tyvaso™ (treprostinil) inhalation solution [online]. Available from URL: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022387LBL.pdf [Accessed 2010 May 17]

    Google Scholar 

  40. Novartis AG. Annual report 2008. Basel: Novartis AG, 2009

    Google Scholar 

  41. Yin W. R&D policy, agency costs and innovation in personalized medicine. J Health Econ 2009 Sep; 28 (5): 950–62

    Article  PubMed  Google Scholar 

  42. European Commission. Morbus Fabry: Europäische Kommission erteilt erstmals Genehmigung fürzwei Arzneimittel zur Behandlung von seltenen Leiden. Brussels: European Commission, 2001

    Google Scholar 

  43. National Institute for Health and Clinical Excellence. About NICE guidance: what does it mean for me? Information for patients, carers and the public: an interim guide. 2007 [online]. Available from URL: http://www.nice.org.uk/nicemedia/pdf/AboutGuidance.pdf [Accessed 2010 Sep 3]

    Google Scholar 

  44. Danzon PM, Furukawa MF. Prices and availability of pharmaceuticals: evidence from nine countries. Health Aff (Millwood) 2003 Jul-Dec; Suppl.Web Exclusives:W3-521-36

    Google Scholar 

  45. Magazzini L, Pammolli F, Riccaboni M. Dynamic competition in pharmaceuticals. Patent expiry, generic penetration, and industry structure. Eur J Health Econ 2004 Jun; 5 (2): 175–82

    Google Scholar 

  46. Danzon PM, Furukawa MF. Prices and availability of biopharmaceuticals: an international comparison. Health Aff (Millwood) 2006 Sep-Oct; 25 (5): 1353–62

    Article  Google Scholar 

  47. Roll K, Stargardt T, Schreyögg J. Authorization and reimbursement of orphan drugs in an international comparison. Gesundheitswesen. Epub 2010 Sep 16

    Google Scholar 

  48. Gericke CA, Riesberg A, Busse R. Ethical issues in funding orphan drug research and development. J Med Ethics 2005 Mar; 31 (3): 164–8

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by a research grant from the Federal Ministry for Research and Education in Germany (grant number: BMBF 01FG09007). The sponsor had no role in the study design, collection and analysis of data, the writing of the report or the submission of the paper for publication. In addition, the authors would like to thank the Munich Center of Health Sciences (MC-Health) for interesting discussions and helpful comments. Finally, the authors want to express their gratitude to the very helpful and supportive comments of the three anonymous reviewers.

The authors have no conflicts of interest that are directly related to the content of this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carl Rudolf Blankart.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blankart, C.R., Stargardt, T. & Schreyögg, J. Availability of and Access to Orphan Drugs. Pharmacoeconomics 29, 63–82 (2011). https://doi.org/10.2165/11539190-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11539190-000000000-00000

Keywords

Navigation