Drivers of managed entry agreements to reduce reimbursement challenges of orphan medicinal products: the development of a matrix

Background: Reimbursing orphan medicinal products (OMPs) presents both opportunities and challenges for national healthcare payers and health technology assessment (HTA) bodies because of their potential high benefits, large clinical uncertainties and high prices. To support a more structured application of (outcome-based) managed entry agreements (MEAs) intended to mitigate these OMP-related reimbursement challenges, a matrix was developed to facilitate reimbursement negotiations and, ultimately, patient access. Methods: A systematic literature review was performed, searching PubMed, Embase, and grey literature from 1 January 2000 until 1 January 2024 to globally identify reimbursement challenges (clinical-, cost-effectiveness uncertainties, or financial risks) described in relation to MEAs for OMPs. The data retrieved were used to develop a matrix that structures the drivers of managed access agreements to reduce financial risk and reimbursement challenges specific to OMPs. Results: A total of 77 studies were included in the review, identifying 23 different types of MEAs for OMPs. The results indicated that more commonly known MEAs were designed to mitigate different reimbursement challenges, and more innovative MEAs and combinations thereof have been frequently described in literature. The selected case study of Myozyme® illustrated how the matrix can present stakeholders with additional mitigation strategies for the relevant reimbursement challenges. Conclusion: To address reimbursement challenges for OMPs along their life cycle, it is valuable to consider both established and innovative, e.g., outcome-based MEAs. Combining reimbursement and payment models has the potential to address multifaceted reimbursement challenges. The developed matrix fills a gap in providing a structure for drivers of MEAs tailored to OMPs, enhancing decision-making processes and ultimate patient access to OMPs targeting high unmet medical needs.