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Rare Diseases

Up to 36 million people in the European Union (EU) live with a rare disease.

Each rare disease that is eligible for orphan designation in Europe affects no more than 5 in 10,000 people.

However, the cumulative effect of rare diseases is great, and the need for orphan drugs is greater. Indeed, more than 6,000 rare diseases are recognised in the EU, and, while some affect only a handful of patients, others may affect as many as 245,000 people.

Of the 41 positive opinions for new active substances granted by the Committee for Medicinal Products for Human Use in 2022, 17 (~40%) of those were designated as orphan drugs.

If you are developing a small molecule or biologic for a rare disease, you should be aware that orphan drug development brings numerous challenges, including:

  • identifying patients,
  • choosing an appropriate study design,
  • choosing a clinically relevant primary endpoint, and
  • making optimum use of the available clinical data.

In some cases, an orphan disease may be so rare that comprehensive studies are not feasible, and approval under exceptional circumstances may be the most appropriate route to market.

Therefore, designing a registrational strategy which incorporates orphan maintenance considerations is key in the EU.

We have supported the development and approval of numerous orphan drugs, across different therapeutic areas and have an expert understanding of orphan drug development and regulatory science.

Case Study

Recombinant protein – ultra-rare indication


A biotech company planned to submit a marketing authorisation application (MAA) in Europe for a recombinant protein in a rare disease.


We wrote the common technical document (CTD) for an EU MAA submission and responded to questions during the assessment. Prior to submission we submitted a modification to the Paediatric Investigation Plan (PIP), such that the validation check was passed successfully for MAA filing. We also supported maintenance of the orphan designations.


Marketing authorization was granted.

Questions you may have if you are developing a product for a rare disease

  • How do we navigate regulatory challenges for rare diseases?
  • Does our drug/biologic meet the eligibility criteria for orphan drug designation?
  • What are the regulatory advantages of orphan drug designation?
  • Have we thoroughly characterised the rare disease we are targeting, including its natural history, molecular mechanisms and disease progression landscape?
  • How well defined is our target population, its prevalence and incidence across geographical locations?
  • How do the specific diagnostic criteria and eligibility factor into our product development?
  • What data are required to support our MAA?
  • What is the accepted prevalence cut-off for the rare disease we are targeting?
  • How do clinical trials differ for rare diseases?
  • What are the orphan designation criteria we must fulfil?