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Abstract
Objectives The research and development process in the field of rare diseases is characterised by many well-known difficulties, and a large percentage of orphan medicinal products do not reach the marketing approval.
This work aims at identifying orphan medicinal products that failed the developmental process and investigating reasons for and possible factors influencing failures.
Design Drugs designated in Europe under Regulation (European Commission) 141/2000 in the period 2000–2012 were investigated in terms of the following failures: (1) marketing authorisation failures (refused or withdrawn) and (2) drugs abandoned by sponsors during development.
Possible risk factors for failure were analysed using statistically validated methods.
Results This study points out that 437 out of 788 designations are still under development, while 219 failed the developmental process. Among the latter, 34 failed the marketing authorisation process and 185 were abandoned during the developmental process. In the first group of drugs (marketing authorisation failures), 50% reached phase II, 47% reached phase III and 3% reached phase I, while in the second group (abandoned drugs), the majority of orphan medicinal products apparently never started the development process, since no data on 48.1% of them were published and the 3.2% did not progress beyond the non-clinical stage.
The reasons for failures of marketing authorisation were: efficacy/safety issues (26), insufficient data (12), quality issues (7), regulatory issues on trials (4) and commercial reasons (1). The main causes for abandoned drugs were efficacy/safety issues (reported in 54 cases), inactive companies (25.4%), change of company strategy (8.1%) and drug competition (10.8%). No information concerning reasons for failure was available for 23.2% of the analysed products.
Conclusions This analysis shows that failures occurred in 27.8% of all designations granted in Europe, the main reasons being safety and efficacy issues. Moreover, the stage of development reached by drugs represents a specific risk factor for failures.
- orphan medicinal products
- development failure
- European medicines agency
- rare diseases
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Footnotes
Contributors VG prepared the first draft of the manuscript and performed the analysis; AL performed the analysis and contributed to the draft of the manuscript; EB reviewed data and solved conflicting results; FG and SN performed the statistical analysis and prepared figures; JT-F reviewed regulatory data and issues; FB contributed to set up of the methodology; MF performed a consistency check with data from EPARs on paediatric medicinal products and indications; DB provided a general revision of the paper; AC provided a general and final review of the draft.
Funding Part of this work was supported by an unrestricted grant from Celgene International II Sàrl grant number (INTL102955).
Competing interests VG, AL and DB declare that part of this work was supported by an unrestricted grant from Celgene International II Sàrl; EB owns Celgene Stock Options (<0.00001%); no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Unpublished data from the study are not available to anyone other than authors.