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Reforming EU and national orphan drug regulations to improve outcomes for patients with rare diseases

BMJ 2023; 381 doi: (Published 09 May 2023) Cite this as: BMJ 2023;381:e072796
  1. Philip Kranz, researcher1,
  2. Natalie McGauran, researcher1,
  3. Rita Banzi, researcher2,
  4. Can Ünal, researcher1,
  5. Fabian Lotz, researcher1,
  6. Thomas Kaiser, director1
  1. 1Institute for Quality and Efficiency in Health Care, Cologne, Germany
  2. 2Mario Negri Institute for Pharmacological Research, IRCCS, Milan, Italy.
  1. Correspondence to: P Kranz philip.kranz{at}

Philip Kranz and colleagues argue that the alleged superior therapeutic benefit attributed to orphan drugs is often not supported by evidence from clinical trials and propose a reform of EU and national orphan drug regulations

Key messages

  • In Europe, the number of approvals for new drugs targeting rare diseases (orphan drugs) has risen sharply since the introduction of the EU Orphan Regulation in 2000

  • The regulation couples orphan drug status with a label of superior therapeutic benefit at approval in the EU without requiring robust evidence even though the real therapeutic benefit of orphan drugs is often unclear

  • The orphan drug status has knock-on effects on national policies

  • EU and national orphan drug regulations need reform: granting superiority labels only on the basis of robust evidence would incentivise evidence generation, lower orphan drug prices and ultimately improve outcomes in patients with rare diseases

About 30 million people in the European Union (EU) are affected by over 6000 different rare diseases,1 making the lack of available and accessible treatments for rare diseases a major public health issue. The development of drugs for rare diseases (orphan drugs) used to be commercially less attractive owing to small markets.1 This led to legislation to incentivise the development of orphan drugs, such as the EU Orphan Regulation of 2000.2 Since then, the number of orphan drugs approved in the EU has risen sharply—from 63 in the first decade after the regulation came into force to 133 in the second decade; 22 were approved in 2022, indicating that this trend will continue.3 The rise in new orphan drug approvals has been described by the drug industry as “a true EU success story”4 and by patient organisations as “a genuine success, and one that should be celebrated proudly by all.”5 The European Commission …

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