Pharmacoeconomic Profiles of Advanced Therapy Medicinal Products in Rare Diseases: A Systematic Review

Abstract

Background and aim: Advanced Therapy Medicinal Products (ATMPs) are innovative drugs based on genes, tissues, or cells that target rare and severe diseases. ATMPs have shown promising clinical outcomes but are associated with high costs, raising questions about cost-effectiveness. Hence, this systematic review aims to analyze the cost-effectiveness and cost-utility profiles of the European Medicines Agency-authorized ATMPs for treating rare diseases. Methods: A systematic review was conducted following PRISMA guidelines. Studies were identified by searching PubMed, Embase, Web of Science, and ProQuest scientific databases. Economic evaluations reporting incremental cost-effectiveness/utility ratios (ICERs/ICURs) for ATMPs were included. Costs were standardized to 2023 Euros, and a cost-effectiveness plane was constructed to evaluate the results against willingness-to-pay (WTP) thresholds of EUR 50,000, EUR 100,000, and EUR 150,000 per QALY, as part of a sensitivity analysis. Results: A total of 61 studies met the inclusion criteria. ATMPs for rare blood diseases, such as tisagenlecleucel and axicabtagene ciloleucel, were found to be cost-effective in a majority of studies, with incremental QALYs ranging from 1.5 to 10 per patient over lifetime horizon. Tisagenlecleucel demonstrated a positive cost-effectiveness profile in the treatment of acute lymphoblastic leukemia (58%), while axicabtagene ciloleucel showed a positive profile in the treatment of diffuse large B-cell lymphoma (85%). Onasemnogene abeparvovec for spinal muscular atrophy (SMA) showed uncertain cost-effectiveness results, and voretigene neparvovec for retinal diseases was not cost-effective in 40% of studies, with incremental QALYs around 1.3 and high costs exceeding the WTP threshold set. Conclusions: ATMPs in treating rare diseases show promising economic potential, but cost-effectiveness varies across indications. Policymakers must balance innovation with system sustainability, using refined models and the long-term impact on patient outcomes.

Keywords: ATMP; Advanced Therapy Medicinal Products; cost-effectiveness; economic evaluation; gene therapy; rare diseases.

Figure 1

The PRISMA flow diagram of study selection.

Figure 2

Global distribution of economic evaluations included in the review.

Figure 3

Sankey chart of the CE profile of ATMPs and their specific diagnosis. Footnotes: The Sankey diagram depicts the distribution of cost-effectiveness analyses of ATMPs. Each segment represents a particular ATMP, with the flow’s size indicating the number of analyses deemed cost-effective or not. It also shows the relative frequency of the ATMPs for each therapeutic indication. Abbreviations: DLBCL—Diffuse large B-cell lymphoma; ALL—Acute lymphoblastic leukaemia; FL—Follicular lymphoma; SMA—Spinal muscular atrophy; MCL—Mantle cell lymphoma; MM—Multiple myeloma; Cost-effectiveness (CE); RPE 65-IRD: Inherited retinal diseases due to RPE65 variants.

Figure 4

Cost-effectiveness plane stratified by ATMPs and macro-diagnosis. Notes: northeast quadrant: more effective but more costly; southeast quadrant: dominant = more effective and less costly; northwest quadrant: dominated = less effective and more costly; southwest quadrant: less effective but less costly.