Orphan Drugs in Oncology

  • Daria KorchaginaEmail author
  • Szymon Jaroslawski
  • Guy Jadot
  • Mondher Toumi
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 213)


Rare diseases represent a group of conditions affecting a very limited number of patients. Low profitability resulting from the small size of target population coupled with difficulties in conducting the research causes the lack of interest from the pharmaceutical industry. In order to promote research and development of medicines for rare diseases, a special ‘orphan’ legislation was introduced in a number of regions. These measures led to a significant increase in the number of approved orphan molecules. The high per patient cost of orphan drugs, as well the rapid growth of orphan drug sector, raised concerns regarding the sustainable funding of therapies for rare diseases. Rare cancers represent the majority of the current orphan drug market and are often associated with very high revenues. This chapter provides a review of orphan legislations and health technology assessment framework, analyses the position of oncology drugs on the orphan drug market and discusses future perspectives.


Orphan drugs Rare diseases Health policy Oncology Health technology assessment Equity Patient access 


  1. Assmann G, Schmidt U, Drechsler M, Pfannkuche M (2014) Conditional resolutions in the among early benefit assessment. Value Health 17. Available: Accessed 23 Jan 2017
  2. Augustine EF, Adams HR, Mink JW (2013) Clinical trials in rare disease: challenges and opportunities. J Child Neurol 28:1142–1150CrossRefGoogle Scholar
  3. BioSeeker Group (2016) Orphan drugs in oncology drug pipeline updateGoogle Scholar
  4. Bouslouk M (2016) G-BA benefit assessment of new orphan drugs in Germany: the first five years. Expert Opin Orphan Drugs 4:453–455CrossRefGoogle Scholar
  5. Brockis E, Marsden G, Cole A, Devlin N (2016) A review of NICE methods across health technology assessment programmes: differences, justifications and implications. Office of Health EconomicsGoogle Scholar
  6. Buzaglo JS, Miller MF, Karten C, Longacre M, Kennedy V, Leblanc TW (2015) Multiple myeloma patient experience with financial toxicity: findings from the Cancer Experience Registry. Blood 126:874Google Scholar
  7. CDER Small Business and Industry Assistance (2015) Patents and exclusivity. FDA/CDER SBIA ChroniclesGoogle Scholar
  8. Cheng MM, Ramsey SD, Devine EB, Garrison LP, Bresnahan BW, Veenstra DL (2012) Systematic review of comparative effectiveness data for oncology orphan drugs. Am J Manag Care 18:47–62PubMedGoogle Scholar
  9. Clarke JT (2006) Is the current approach to reviewing new drugs condemning the victims of rare diseases to death? A call for a national orphan drug review policy. CMAJ Can Med Assoc J 174:189–190CrossRefGoogle Scholar
  10. Cohen JP, Felix A (2014) Are payers treating orphan drugs differently? J Market Access Health Policy 2. Scholar
  11. Collins M, Latimer N (2013) NICE’s end of life decision making scheme: impact on population health. Br Med J (BMJ) 346Google Scholar
  12. Cote A, Keating B (2012) What is wrong with orphan drug policies? Value Health 15:1185–1191CrossRefGoogle Scholar
  13. Davies JE, Neidle S, Taylor DG (2012) Developing and paying for medicines for orphan indications in oncology: utilitarian regulation vs equitable care[quest]. Br J Cancer 106:14–17CrossRefGoogle Scholar
  14. Drake CG (2012) Combination immunotherapy approaches. Ann Oncol 23:viii41–viii46CrossRefGoogle Scholar
  15. Drummond M, Towse A (2014) Orphan drugs policies: a suitable case for treatment. Eur J Health Econ 15:335–340CrossRefGoogle Scholar
  16. Drummond MF, Wilson DA, Kanavos P, Ubel P, Rovira J (2007) Assessing the economic challenges posed by orphan drugs. Int J Technol Assess Health Care 23CrossRefGoogle Scholar
  17. Emanuel EJ, Miller FG (2001) The ethics of placebo-controlled trials—a middle ground. N Engl J Med 345:915–919CrossRefGoogle Scholar
  18. European Medicines Agency (n.d.-a.) Conditional marketing authorisation (Online). Available: Accessed 23 Jan 2017
  19. European Medicines Agency (n.d.-b.) Marketing authorisation and market exclusivity (Online). Available: Accessed 23 Jan 2017
  20. European Medicines Agency (n.d.-c.) Orphan designation (Online). Available: Accessed 23 Jan 2017
  21. European Parliament and Council Regulation 141/2000/EC, 16 December 1999 on Orphan Medicinal Products. Official J Eur Commun L018/1 (22 Jan 2000)Google Scholar
  22. EvaluatePharma (2013) Orphan drug report 2013Google Scholar
  23. EvaluatePharma (2014) Pharmaceutical & biotech sales analysis by country. Top Drugs, Top RegionsGoogle Scholar
  24. Experts in Chronic Myeloid Leukemia (2013). The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood 121:4439–4442Google Scholar
  25. Feltmate K, Janiszewski PM, Gingerich S, Cloutier M (2015) Delayed access to treatments for rare diseases: who’s to blame? (Review). Respirology 20:361–369CrossRefGoogle Scholar
  26. Gammie T, Lu CY, Babar ZU-D (2015) Access to orphan drugs: a comprehensive review of legislations, regulations and policies in 35 countries. PLoS ONE 10:e0140002CrossRefGoogle Scholar
  27. Gatta G, Van Der Zwan JM, Casali PG, Siesling S, Dei Tos AP, Kunkler I, Otter R, Licitra L, Mallone S, Tavilla A, Trama A, Capocaccia R (2011) Rare cancers are not so rare: the rare cancer burden in Europe. Eur J Cancer 47:2493–2511CrossRefGoogle Scholar
  28. Gibson S, Von Tigerstrom B (2015) Orphan drug incentives in the pharmacogenomic context: policy responses in the US and Canada. J Law Biosci 2:263–291CrossRefGoogle Scholar
  29. Griggs RC, Batshaw M, Dunkle M, Gopal-Srivastava R, Kaye E, Krischer J, Nguyen T, Paulus K, Merkel PA, Network RDCR (2009) Clinical research for rare disease: opportunities, challenges, and solutions. Mol Genet Metab 96:20–26CrossRefGoogle Scholar
  30. Gutierrez L, Patris J, Hutchings A, Cowell W (2015) Principles for consistent value assessment and sustainable funding of orphan drugs in Europe. Orphanet J Rare Dis 10:53CrossRefGoogle Scholar
  31. Hall AK, Ludington E (2013) Considerations for successful clinical development for orphan indications. Expert Opin Orphan Drugs 1:847–850CrossRefGoogle Scholar
  32. Haute Authorité de Santé (2015) Rapport d’activité 2015Google Scholar
  33. Haute Authorité de Santé (n.d.) Haute Autorité de Santé - HAS (Online). Available: Accessed 23 Jan 2017
  34. Hughes D (2006) Rationing of drugs for rare diseases. Pharmacoeconomics 24:315–316CrossRefGoogle Scholar
  35. Hughes DA, Tunnage B, Yeo ST (2005) Drugs for exceptionally rare diseases: do they deserve special status for funding? QJM 98CrossRefGoogle Scholar
  36. Hughes-Wilson W, Palma A, Schuurman A, Simoens S (2012) Paying for the Orphan Drug System: break or bend? Is it time for a new evaluation system for payers in Europe to take account of new rare disease treatments? Orphanet J Rare Dis 7:74CrossRefGoogle Scholar
  37. Hyry HI, Stern AD, Cox TM, Roos JC (2014) Limits on use of health economic assessments for rare diseases. QJM 107:241–245CrossRefGoogle Scholar
  38. Hyry HI, Roos JC, Cox TM (2015) Orphan drugs: expensive yet necessary. QJM 108:269–272CrossRefGoogle Scholar
  39. Kantarjian HM, Fojo T, Mathisen M, Zwelling LA (2013) Cancer drugs in the United States: Justum Pretium—the just price. J Clin Oncol 31:3600–3604CrossRefGoogle Scholar
  40. Kanters TA, Steenhoek A, Hakkaart L (2014) Orphan drugs expenditure in the Netherlands in the period 2006–2012. Orphanet J Rare Dis 9:154CrossRefGoogle Scholar
  41. Kawalec P, Sagan A, Pilc A (2016) The correlation between HTA recommendations and reimbursement status of orphan drugs in Europe. Orphanet J Rare Dis 11:122CrossRefGoogle Scholar
  42. Khera N (2014) Reporting and grading financial toxicity. J Clin Oncol 32:3337–3338CrossRefGoogle Scholar
  43. Kolasa K, Zwolinski KM, Kalo Z, Hermanowski T (2016) Potential impact of the implementation of multiple-criteria decision analysis (MCDA) on the Polish pricing and reimbursement process of orphan drugs. Orphanet J Rare Dis 11:23CrossRefGoogle Scholar
  44. Korchagina D, Remuzat C, Rodrigues J, Kornfeld A, Toumi M (2014) Health technology assessment, price and reimbursement review for orphan drugs in France. Value Health 17:A540. Available: Accessed 23 Jan 2017
  45. Korchagina D, Miullier A, Vataire AL, Aballéa S, Falissard B, Toumi M (2016) Determinants of orphan drugs prices in France: a regression analysis. Orphanet J Rare Dis (in press)Google Scholar
  46. Le Cam Y (2010) Inventory of access and prices of orphan drugs across Europe: a collaborative work between National Alliances on rare Diseases & Eurordis. ParisGoogle Scholar
  47. Leverkus F, Chuang-Stein C (2015) Implementation of AMNOG: an industry perspective. Biom J 58:76–88CrossRefGoogle Scholar
  48. Loughnot D (2005) Potential interactions of the Orphan Drug Act and pharmacogenomics: a flood of orphan drugs and abuses? Am J Law Med 31:365–380CrossRefGoogle Scholar
  49. Macarthur D (2008) Orphan drugs in Europe: pricing, reimbursement, funding and market access issuesGoogle Scholar
  50. Marsh K, Ijzerman M, Thokala P, Baltussen R, Boysen M, Kaló Z, Lönngren T, Mussen F, Peacock S, Watkins J (2016) Multiple criteria decision analysis for health care decision making—emerging good practices: report 2 of the ISPOR MCDA Emerging Good Practices Task Force. Value Health 19:125–137CrossRefGoogle Scholar
  51. Marshall T (2005) Orphan drugs and the NHS: consider whom drug regulation is designed to protect. BMJ 331:1144CrossRefGoogle Scholar
  52. Mcdougall J, Ramsey S, Ya-Chen T (2014) Financial toxicity: a growing concern among cancer patients in the United States. ISPOR Connect 20Google Scholar
  53. Meekings KN, Williams CS, Arrowsmith JE (2012) Orphan drug development: an economically viable strategy for biopharma R&D. Drug Dis Today 17:660–664CrossRefGoogle Scholar
  54. Miller KL, Lanthier M (2016) Trends in orphan new molecular entities, 1983–2014: half were first in class, and rare cancers were the most frequent target. Health Aff 35:464–470CrossRefGoogle Scholar
  55. Ministry of Health, Labour and Welfare (n.d.) Overview of orphan drug/medical device designation system (Online). Available: Accessed 23 Jan 2017
  56. Murphy SM, Puwanant A, Griggs RC (2012) Unintended effects of orphan product designation for rare neurological diseases (Review). Ann Neurol 72:481–490CrossRefGoogle Scholar
  57. Mycka J, Dellamano R, Lobb W, Dellamano L, Dalal N (2015) Orphan drugs assessment in Germany: a comparison with other international agencies. Value Health 18. Available: Accessed 23 Jan 2017
  58. National Institute for Health and Care Excellence (2013) Highly specialised technologies programme: interim process and methodsGoogle Scholar
  59. National Institute for Health and Care Excellence (2017) Interim process and methods of the highly specialised technologies programme updated to reflect 2017 changesGoogle Scholar
  60. National Institute for Health and Care Excellence (n.d.) NICE | The National Institute for Health and Care Excellence (Online). NICE. Available: Accessed 23 Jan 2017
  61. NHS England Cancer Drugs Fund Team (2016) Appraisal and funding of cancer drugs from July 2016 (including the new Cancer Drugs Fund)—a new deal for patients, taxpayers and industryGoogle Scholar
  62. Orphan Drug Act (1983) Public law 97-414. United States of AmericaGoogle Scholar
  63. Overacre AE, Kurtulus S, Sznol M, Pardoll DM, Anderson A, Vignali DA (2015) Combination immunotherapy: where do we go from here? J ImmunoTherapy Cancer 3:38CrossRefGoogle Scholar
  64. Paulden M, Stafinski T, Menon D, Mccabe C (2015) Value-based reimbursement decisions for orphan drugs: a scoping review and decision framework. Pharmacoeconomics 33:255–269CrossRefGoogle Scholar
  65. Picavet E, Dooms M, Cassiman D, Simoens S (2011) Drugs for rare diseases: influence of orphan designation status on price. Appl Health Econ Health Policy 9:275–279CrossRefGoogle Scholar
  66. Picavet E, Cassiman D, Hollak CE, Maertens JA, Simoens S (2013) Clinical evidence for orphan medicinal products-a cause for concern? Orphanet J Rare Dis 8:164CrossRefGoogle Scholar
  67. Picavet E, Morel T, Cassiman D, Simoens S (2014) Shining a light in the black box of orphan drug pricing. Orphanet J Rare Dis 9:62CrossRefGoogle Scholar
  68. Provost G (1968) “Homeless” or “orphan” drugs. Am J Health-Syst Pharm 25:609Google Scholar
  69. Rémuzat C, Toumi M, Falissard B (2013) New drug regulations in France: what are the impacts on market access? Part 1—overview of new drug regulations in France. J Mark Access Health Policy 1Google Scholar
  70. Richter T, Nestler-Parr S, Babela R, Khan ZM, Tesoro T, Molsen E, Hughes DA (2015) Rare disease terminology and definitions—a systematic global review: report of the ISPOR rare disease special interest group. Value Health 18:906–914CrossRefGoogle Scholar
  71. Rodrigues J, Korchagina D, Rémuzat C, Brunet J, Tavella F (2014) Orphan drug approvals in Europe: historical review and trends. Value Health 17:A539 Available: Accessed 23 Jan 2017
  72. Schey C, Milanova T, Hutchings A (2011) Estimating the budget impact of orphan medicines in Europe: 2010–2020. Orphanet J Rare Dis 6:62CrossRefGoogle Scholar
  73. Schlander M, Garattini S, Holm S, Kolominsky-Rabas P, Nord E, Persson U, Postma M, Richardson J, Simoens S, De Sola MO, Tolley K, Toumi M (2014) Incremental cost per quality-adjusted life year gained? The need for alternative methods to evaluate medical interventions for ultra-rare disorders. J Comp Eff Res 3:399–422CrossRefGoogle Scholar
  74. Schuller Y, Hollak CEM, Biegstraaten M (2015) The quality of economic evaluations of ultra-orphan drugs in Europe—a systematic review. Orphanet J Rare Dis 10:92CrossRefGoogle Scholar
  75. Sheehan M (2005) Orphan drugs and the NHS: fairness in health care entails more than cost effectiveness. BMJ 331:1144–1145CrossRefGoogle Scholar
  76. Simoens S (2011) Pricing and reimbursement of orphan drugs: the need for more transparency. Orphanet J Rare Dis 6CrossRefGoogle Scholar
  77. Simoens S (2014) Health technologies for rare diseases: does conventional HTA still apply? Expert Rev Pharmacoecon Outcomes Res 14:315–317CrossRefGoogle Scholar
  78. Simoens S, Picavet E, Dooms M, Cassiman D, Morel T (2013) Cost-effectiveness assessment of orphan drugs: a scientific and political conundrum. Appl Health Econ Health Policy 11:1–3CrossRefGoogle Scholar
  79. Song P, Gao J, Inagaki Y, Kokudo N, Tang W (2012) Rare diseases, orphan drugs, and their regulation in Asia: current status and future perspectives. Intractable Rare Dis Res 1:3–9PubMedPubMedCentralGoogle Scholar
  80. Sussex J, Rollet P, Garau M, Schmitt C, Kent A, Hutchings A (2013) A pilot study of multicriteria decision analysis for valuing orphan medicines. Value Health 16:1163–1169CrossRefGoogle Scholar
  81. Thomson Reuters (2012) The economic power of orphan drugsGoogle Scholar
  82. Tordrup D, Tzouma V, Kanavos P (2014) Orphan drug considerations in health technology assessment in eight European countries. Int J Public Health 1Google Scholar
  83. US Food and Drug Administration (2014) Guidance for Industry. Expedited Programs for Serious Conditions—Drugs and BiologicsGoogle Scholar
  84. US Food and Drug Administration (2016) Orphan products clinical trials grants program (Online). Available: Accessed 23 Jan 2017
  85. US Food and Drug Administration (2017) Developing products for rare diseases and conditions (Online) Available: Accessed 23 Jan 2017
  86. Wagner M, Khoury H, Willet J, Rindress D, Goetghebeur M (2016) Can the EVIDEM framework tackle issues raised by evaluating treatments for rare diseases: analysis of issues and policies, and context-specific adaptation. Pharmacoeconomics 34:285–301CrossRefGoogle Scholar
  87. Westermark K, Llinares J (2012) Promoting the development of drugs against rare diseases: what more should be done? Expert Rev Pharmacoecon Outcomes Res 12:541–543CrossRefGoogle Scholar
  88. Winquist E, Bell CM, Clarke JT, Evans G, Martin J, Sabharwal M, Gadhok A, Stevenson H, Coyle D (2012) An evaluation framework for funding drugs for rare diseases. Value Health 15:982–986CrossRefGoogle Scholar
  89. Zafar SY (2016) Financial toxicity of cancer care: it’s time to intervene. J Nat Cancer Inst 108:djv370Google Scholar
  90. Zafar SY, Peppercorn JM, Schrag D, Taylor DH, Goetzinger AM, Zhong X, Abernethy AP (2013) The financial toxicity of cancer treatment: a pilot study assessing out-of-pocket expenses and the insured cancer patient’s experience. Oncologist 18:381–390CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Daria Korchagina
    • 1
    Email author
  • Szymon Jaroslawski
    • 2
  • Guy Jadot
    • 3
  • Mondher Toumi
    • 2
  1. 1.Mental Health and Public HealthParisFrance
  2. 2.Public Health DepartmentAix-Marseille UniversityMarseilleFrance
  3. 3.Laboratory P2S Systemic Health, Laennec Faculty of MedicineClaude Bernard University Lyon 1LyonFrance

Personalised recommendations