EMA approved orphan medicines since the implementation of the orphan legislation

Abstract

Background: In the European Union (EU), the orphan legislation, aiming to increase the number of pharmacotherapies available for rare diseases, came into force in April 2000. This study examined the development of the selection of orphan medicines granted marketing authorisation, their approved indications, and the number of orphan medicines developed for paediatric use in EU during 2000-2022. This study also examined the availability of the orphan medicines with a marketing authorisation in the Finnish market in order to demonstrate their country level uptake in a single member state.

Methods: The material on orphan medicines' marketing authorisations and their introduction were collected from the European Commission's Community Registers in June 2022 and analysed with a qualitative document analysis. This study covered the period 2000-2022 since the introduction of the orphan legislation, and comparisons were made in 10-year periods of, 2001-2010 and 2011-2020.

Results: By May 2022, there were 213 novel orphan medicines approved in Europe during the observation period. Of them, 67% (n = 142) were on the market in Finland in May 2024. The number of new orphan medicines approved in Europe doubled from 63 products in 2001-2010 to 127 products in 2011-2020. Several orphan medicines were developed for certain type of rare diseases, such as haematological cancers. The proportion of orphan medicines approved for paediatric use decreased from 55% in 2001-2010 to 42% in 2011-2020.

Conclusion: The number of orphan medicines available within EU increased significantly after the orphan legislation came into force. The development of orphan medicines seemed to often focus on diseases or disease groups that already have available treatment options, while several rare diseases remain without available treatment. Even though rare diseases are more common in children, orphan medicines have not been developed for paediatric use in the same proportion.

Keywords: Europe; Orphan medicine; Orphan medicines legislation; Rare disease; Selection of medicines.

Fig. 1

Orphan medicinal products approved in the EU during 2000–2022 and included in the research material (n = 269).¹The number of active substances is different from the number of novel orphan medicines because two active substances were granted marketing authorisation as two new orphan medicinal products for different indications. ² Same therapeutic indications may be approved for the orphan medicines in this box; therefore, this illustrates the number of completely different therapeutic indications. ³Including extensions of indications

Fig. 2

Orphan medicinal products on the market in Finland in May 2024 (n = 142). ¹Not including extensions of indications. ²The number of orphan medicines is different from the sum of orphan medicines with valid orphan designation and orphan medicine with expired orphan designation because four medicinal products have valid and expired orphan designation for different indications. ³Four medicinal products had valid and expired orphan designation for different indications. ⁴Classified by dosage form. Infusions are classified as medicine used in inpatient care; other medicines are classified as outpatient medicines

Fig. 3

Marketing authorisations granted for orphan medicines per year and the number of valid marketing authorisations for orphan-designated medicines on 31 May 2022

Fig. 4

Orphan medicines classified by marketing authorisations per year and divided into three categories according to therapeutic indications: inborn errors of metabolism or immune disorders; cancer; and other diseases

Fig. 5

Orphan medicines approved for paediatric or paediatric and adult indication (n = 124) compared to orphan medicines approved only for adults (n = 145)