When prevention constrains cure: Institutional lock-in and gene therapy access for beta-thalassemia

On 16 November 2023, the United Kingdom Medicines and Healthcare products Regulatory Agency approved Casgevy (exagamglogene autotemcel), the first CRISPR-based gene therapy for a genetic disease, offering patients with transfusion-dependent beta-thalassemia (TDT) freedom from lifelong monthly transfusions. Yet in China, which carries the world's largest TDT patient population, no patient has received the therapy through the public health system, and the access gap is not explained by price or manufacturing economics alone. This paper argues that prevention-era institutional architecture constrains cure-era access through three lock-in mechanisms: cognitive (the direction of genetic information flow), infrastructural (the spatial distribution of treatment capacity), and fiscal (the structure of payment responsibility). Drawing on a structured comparison of four countries selected to represent distinct institutional pathway types (Cyprus, ecclesiastical-public certification; China, administrative filing; Thailand, public health universal coverage; India, federal fragmentation), the analysis proposes a typology of barrier configurations and illustrates them through four exploratory cases. The administrative-filing pathway is associated with high barriers across information, geographic, and economic dimensions; trust-intention is not assessable on current evidence. The ecclesiastical-public pathway is associated with medium information and low geographic barriers with medium fiscal and low-confidence trust barriers; the universal-coverage pathway provides a balanced platform that remains under-activated for gene therapy; and the federal-fragmented pathway fails the precondition of patient identification. No pathway simultaneously optimizes all four readiness dimensions. Presented as a hypothesis-generating typology rather than a tested diagnostic model, the framework relates pathway type to barrier configuration and offers testable hypotheses for pathway-specific intervention design and for extension to sickle cell disease, hemophilia, and other genetic conditions entering the curative era.