Assessing Health Technology Assessment (HTA) Outcomes for Conditionally Approved Drugs by the European Medicines Agency (EMA) in Germany, France, and England

OBJECTIVES: The EMA grants conditional marketing authorizations (C-MA) to medicines for debilitating/life-threatening diseases, including orphan drugs, when the benefits of faster availability outweigh the risks. C-MAs are valid for one year, renewable annually, with specific obligations to be fulfilled within set timelines. This study analyzes HTA outcomes in Germany, France, and England for medicines granted C-MA.

METHODS: Products granted C-MA (2018-2021) were identified. Approvals after 2021 were excluded due to insufficient time for reimbursement procedures. Certain drug classes (e.g., ATMPs, biosimilars, vaccines) were excluded. HTA outcomes were extracted from publicly available HTA opinions in Germany, France, and England (June 2024).

RESULTS: Of 34 products receiving C-MA, 22 were included in the analysis (orphan, n=11; non-orphan, n=11). Average time to reimbursement for non-orphans with C-MA was longer than for all drugs across countries, and longer than for orphans with C-MA in France (29.2 vs 22.2 months) and Germany (10.0 vs 8.6 months). Orphan products with C-MA took longer to reimburse than standard-approved orphan products in England (16.3 vs 11.9 months) and Germany (8.6 vs 2.9 months; 3x longer). In England, timelines were longer for negative outcomes.

Products were reimbursed as per the EMA label most frequently in Germany (96%) followed by England (50%) and France (32%). More non-orphan vs orphan products were reimbursed: Germany (55% vs 41%), England (27% vs 23%), France (18% vs 14%). In England, ~50% were included in the Cancer Drugs Fund to collect additional evidence. In Germany, one drug received “considerable additional benefit” while others had “unproven” or “non-quantifiable” benefit due to lack of data. France had the highest denial rate (18%), followed by England (14%), with none in Germany.

CONCLUSIONS: C-MAs lead to extended reimbursement decision timelines compared to standard approvals, regardless of orphan status. These delays highlight challenges in achieving timely market access even with expedited regulatory pathways.