Résumé
Background: EU Orphan Regulation (EC) n° 141/2000 has catered for accelerate time to market for new medicines and for increase access. However, substantial challenges subsist and patient access to medicines on a national level remains very heterogeneous across Europe.Objectives: this study aims to investigate factors influencing time to reimbursement (TTR) in five high-incomeEuropean countries.Materials and methods: a retrospective case study of orphan medicines with European Marketing Authorisation(Eu-MA) was carried out using reimbursement data from Germany, France, the United-Kingdom, Italy, and Spain.Multivariate Cox proportional hazard regression analysis was used to investigate indication-, medication-,pharmaceutical company- and country-related factors potentially influencing reimbursement.Results: eighty-one orphan drugs were identified using the EMA database between January 1, 2017 to July 1,2022 for which time to reimbursement ranged from 0 days to 2,495 days (median 506 days). At data cut-off, 38(47%) were reimbursed in all five countries. In multivariate analysis, time to reimbursement was significantlyshorter in Germany compared to the other countries (p<0.001) and was also significantly shorter for oncology drugs (p=0.001).Conclusion: even in high-income European countries, the reimbursement time of orphan drugs is variable andlengthy. National policies and regulations as well as the anticancer status have a significant impact on thereimbursement time of orphan medicines . Reducing disparities in access among countries will require newharmonization measures at the European level, the first for orphan drugs will be the Joint Clinical Assessment in2028.