Rare Diseases – where are we now? Featured Image

Rare Diseases – where are we now?

26 Feb 21

By Birge Berns

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28 February 2021 is rare disease day. An opportunity to reflect on the achievements in this space to date, as well as the challenges we are facing. 

A particular rare disease may affect fewer than 1 in 100,000 people. But between 5,000 and 8,000 distinct rare diseases exist, meaning they are affecting between 6% and 8% of the population in total. 300 million people live with rare diseases worldwide, approximately 30 million in Europe.

Yet medical and scientific progress has been slow – fewer than 1,000 diseases benefit from even minimal amounts of scientific knowledge. The pharmaceutical industry focus has shifted to orphan indications where success has already been demonstrated, such as Cystic Fibrosis or Interstitial Pulmonary Fibrosis. Up to 95% of rare diseases still do not have treatment options today.

80% of rare diseases have identifiable genetic origins and affect between 3% and 4% of births. Other rare diseases are due to degenerative and proliferative causes. Some 60% of designated orphan medicines are intended for paediatric use.

The European Medicines Agency (EMA) plays a central role in facilitating the development and authorisation of medicines for rare diseases. The EU regulation on medicines for rare diseases (orphan medicines) (2000) and the paediatric medicines regulation (2006) are meant to increase therapeutic choices for patients suffering from rare diseases and children. The orphan regulation rewards applicants through incentives, whereas the paediatric regulation works through obligations, which can take time and effort to complete. The number of applications for orphan designations in 2019 was 233, reflecting the steady identification of new targets to treat orphan diseases. Of these, 113 were granted an orphan designation, allowing them to benefit from the incentives under the EU Orphan Framework. Since the year 2000, over 2,233 orphan designations have been issued by the European Commission, of which so far 169 have resulted in authorised medicinal products. In 2019, the EMA’s Paediatric Committee (PDCO) agreed 94 initial Paediatric Investigational Plans (PIPs), the highest number in the past five years.

In August 2020 the European Commission published a joint report, evaluating these 2 regulations. The report states both regulations have fostered the development and availability of medicines in these areas. Similarly, figures from the US in 2020 demonstrate 31 out of 53 (58%) novel drug approvals by FDA were approved to treat rare (orphan) diseases that affect 200,000 or fewer Americans.

However, looking more closely at the details in Europe, both the rare disease and paediatric regulations have not adequately managed to support development where the need for medicines is greatest. The report questions whether the threshold for an orphan disease affecting fewer than 5 in 10,000 patients is the right tool for identifying patients with rare diseases. The paediatric regulation has no dedicated instrument to direct development to areas truly relevant to children.

Challenges to drug development remain and require our attention:

  • Understanding disease biology, often genetic in origin. With advances in cell and gene therapy, it has now become feasible to treat some of these ultra-rare diseases
  • Manufacture of these advanced therapies: manufacturing processes are complex, subject to increased variability and high expense
  • Small number of patients available for trials in any one disease. Can we create common platforms for testing?
  • Clinical trial design – enrolment and retention of patients
  • Substantial evidence usually required for regulatory approval
  • Commercial viability in such a small market

We need to collaborate and come forward with solutions to take to regulatory agencies and payers.


  1. Orphan medicines in the EU_2020 UPDATE – Copy (europa.eu)
  2. Annual report on the use of the special contribution for orphan medicinal products – 2019 (europa.eu)
  3. Evaluation of the medicines for rare diseases and children legislation | Public Health (europa.eu) 
  4. New Drugs Approval Report 2020 (fda.gov) 
  5. Special Populations in PHEs (II): Rare Diseases | FPM

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