Timing and rate of reimbursement for cystic fibrosis modulator therapies in EU countries

BACKGROUND: In the EU, Cystic Fibrosis modulator therapies (CFTR modulators) are centrally licensed, but reimbursement is determined at the national level, resulting in variations in access. This study examined cross-country differences in timing and rate of reimbursement for CFTR modulators, exploring determinants of reimbursement timelines across Europe. METHODS: Retrospective data on marketing authorisation, national reimbursement dossier submission, and reimbursement dates were collected for all CFTR modulators authorised in the EU across the 27 Member States. Kaplan-Meier methods were applied to analyse time to reimbursement from marketing authorisation (TTR) and from national reimbursement submissions (TTR2). A mixed-effects Cox proportional hazards model was used to identify determinants of reimbursement timelines. RESULTS: As of 31 December 2024, the median TTR for CFTR modulators was 1479 days (95% CI: 1162-1691), with 62% of EU-approved indications reimbursed, while TTR2 decreased to 280 days (95% CI: 230-322). More recently authorised products were reimbursed faster, and extensions of indication for the same drug were associated with shorter TTRs. Higher Gross Domestic Product per capita and a larger pool of prevalent cystic fibrosis cases were associated with faster reimbursement. Random-effects estimates indicate substantial residual heterogeneity at the country level. CONCLUSIONS: There is considerable variability in the timing and rate of reimbursement for CFTR modulators across EU countries, primarily determined by the timing of manufacturer submissions to national authorities. While our findings point to a learning process in reimbursement practice over time, variations nonetheless arise from economic, epidemiological, and other structural factors, suggesting that smaller and less wealthy countries often face delays in reimbursement.