Raif Kaan BAŞ, Ayşe Arzu SAKUL
Cam and Sakura Medical Journal - 2026;6(2):36-43
Gene and cell therapies represent a paradigm shift in medicine, offering the prospect of durable or curative benefit from a single administration; however, they are associated with unprecedented upfront prices, routinely exceeding two to three million US dollars per patient. This combination-a one-time intervention whose clinical value accrues over a lifetime while its full cost is incurred immediately-strains the conventional methods of pharmacoeconomic evaluation and confronts payers with acute affordability and equity challenges. This review examines how the cost-effectiveness of these therapies is assessed within the single-dose, high-price paradigm and what methodological adaptations the paradigm demands. We first describe the economic distinctiveness of one-time therapies and the core analytic problems they raise: the profound uncertainty about the durability of effect; the reliance on single-arm trials and surrogate endpoints; the disproportionate influence of the discount rate; and the limitations of the quality-adjusted life-year (QALY) in capturing value for severe, rare paediatric conditions. We then synthesise the published economic evidence through detailed case studies of spinal muscular atrophy (onasemnogene abeparvovec) and Duchenne muscular dystrophy (delandistrogene moxeparvovec), and through further exemplars in chimeric antigen receptor T-cell therapy, haemophilia, and sickle-cell disease and beta-thalassaemia. Reported incremental cost-effectiveness ratios vary enormously-from dominant or highly cost-effective to several million euros per QALY-driven chiefly by assumptions about durability, comparator cost, and discounting. We review novel financing and access mechanisms, including outcomes-based agreements, annuity payments, and public access models, and situate the discussion within the context of divergence in international health technology assessment, recent market withdrawals, and the Turkish reimbursement environment. Robust, transparent, and durability-sensitive economic evaluation, coupled with innovative payment models, will be essential to reconcile access with sustainability.
