Failures to further developing orphan medicinal products after designation granted in Europe: an analysis of marketing authorisation failures and abandoned drugs

Abstract

ObjectivesThe 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.DesignDrugs 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period 2000–2012 were investigated in terms of the following failures: (1) marketing authorisation failures (refused or withdrawn) and (2) drugs abandoned by sponsors during development.Possible risk factors for failure were analysed using statistically validated methods.ResultsThis study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.ConclusionsThis 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.

Application of orphan drug designation to cancer treatments (2008–2017): a comprehensive and comparative analysis of the USA and EU

“…Less than 50% of cancer drugs with orphan designation by the FDA received such status in the EMA. Our results are consistent with other studies showing that the USA has more orphan drug designations in general and specifically for oncology drugs compared with the EU 21 27 28. Drugs that targeted biomarker-defined subsets of common cancer types often received orphan status in the USA, but did not get similar status in the EU.…”

Has OMP legislation been successful? Yes, though the orphan drug market remains immature

“…Even more, when we look at the last 5 years (2011-15), the proportion of treatments that proceed to market is even more discouraging, and only 4,4% (18 drugs) of those positive opinions are marketed (range 0-12%). In an analysis of the first decade of approvals by EMA (2000-2012), Giannuzzi [16] showed that a large number of drugs never started development (abandoned drugs) whereas for those there was a development 47% reached phase III, but still point to bankruptcy as the second cause for discontinuation of approval process, possibly linked to their small size and financial capacity.…”

Survey of Japanese Orphan Drug Program: Factors Related to Successful Marketing Approval

“…The choice of explanatory variables was based on the analysis of previous studies. [17][18][19] The number of patients, availability of alternative treatment, company size of the applicant (3000ࣚ or <3000 employees), nationality of the applicant, experience with orphan drug development in Japan, new molecular entity, and Anatomical Therapeutic Chemical classification were used as explanatory variables. Drugs under the Anatomical Therapeutic Chemical classification B, C, D, G, H, M, P, R, S, and V, each of which comprised <10% of the total data set, were grouped together in logistic regression.…”