OBJECTIVES: This study aimed to identify challenges and potential solutions in attaining successful market access for ATMPs (advanced therapy medicinal products) in Europe.

METHODS: A targeted review of ATMPs approved in the EU, country-specific market access (MA) legislation for the major 4EU markets, health technology assessment (HTA) reports, and literature was conducted for the period 2009 to 2022.

RESULTS: During the review period, EMA issued 26 positive draft opinions, of which 19 were designated orphan drug status.

Nine companies withdrew marketing authorizations due to challenges in product reimbursement caused by limited patient populations and costly manufacturing processes.

The main objections to reimbursement at the national level include trial design and lack of evidence availability such as small patient numbers, single-arm or non-randomized controlled studies, trial duration, and lack of established competitors. However, country-specific hurdles need to be considered.

In Italy, reimbursement challenges focus on assessing the added value of ATMPs compared to existing therapies at national and regional levels. In Germany, payer restrictions for orphan ATMPs are tightened due to additional requirements, mandating use in specialized centres. In France, achieving an improvement score (ASMR) of I-III without survival data versus the standard of care (SOC) treatment with single-arm trial data is difficult, whilst, in Spain, regional budgets impact the uptake of high-cost ATMPs.

CONCLUSIONS: Whilst orphan drugs have a higher likelihood of attaining reimbursement, the challenges surrounding ATMPs warrant harmonization of frameworks across regulators and HTA agencies to streamline reimbursement. Manufacturers can strengthen their MA strategy by seeking scientific and payer advice as early as possible to align on ATMP evidence requirements, thereby building engagement strategies with stakeholders across the sector to support MA.