Innovative Reimbursement Agreements Addressing the Challenges of Advanced Therapy Medicinal Products: Systematic Review for the Five Major European Healthcare Systems (EU5)

OBJECTIVES: Advanced therapy medicinal products (ATMP) hold great promise to deliver transformative effects in the treatment of severe and orphan conditions. Their high short-term budget impact and associated uncertainties regarding their long-term efficacy pose challenges for reimbursement. The primary objective of this review was to gain insight into the types of reimbursement agreements used for the funding of ATMPs in the statutory health insurance systems across the five major European countries (EU5). The secondary objective was to examine the outcomes of the assessment of ATMPs in national Health Technology Assessments (HTA).

METHODS: For this systematic review all records on reimbursement agreements for ATMPs in the EU5 until 24/08/2023 were considered. Medline, Embase, Scopus, Web of Science and national HTA websites were systematically searched.

RESULTS: 43 records, and 141 HTA reports were included in the synthesis. Despite the disruptive nature of ATMPs, payers across the EU5 can assess their value and inform reimbursement decisions with minor adjustments of established pathways. The individual reimbursement agreements went beyond traditional drug pricing mechanisms. The urge for ATMPs led to temporal decoupling of reimbursement and completed evidence generation. Marketing authorization holders (MAH) are already receiving payments while they are collecting data on the long-term efficacy. France and the United Kingdom (UK) used coverage with evidence development agreements, while Germany, Italy and Spain used outcomes-based risk sharing agreements.

CONCLUSIONS: Managed entry agreements linking the reimbursement of ATMPs to their outcomes in the clinical practice address their challenges and have the potential to enable sustainable market access.