OBJECTIVES : The betibeglogene autotemcel (beti-cel) health-economic evaluation in β-thalassemia compares two “asymmetric” treatments: the one-time administration with potentially life-long effect gene therapy and a chronic life-long treatment (transfusions and iron chelation). The evaluation conducted by the French health authority (HAS) demonstrated that the health-economic evaluation framework needs adaptation, due to this asymmetry. The objective of this analysis is to highlight why this framework should evolve to meaningfully assess gene therapies efficiency with the example of beti-cel.

METHODS : The cost-effectiveness analysis carried out to evaluate the beti-cel efficiency in France was used to show the value of modifying the evaluation framework for this type of comparison. Significant parameters of interest were time horizon and perspective. Each parameter was chosen according to the HAS’ framework and to be the most relevant for this therapy: a 30-year time horizon versus a lifetime; and a collective perspective (all payers except indirect costs) versus a societal perspective. The impact of these parameters was analyzed and discussed.

RESULTS : With a 30-year time horizon, chosen by the HAS, only 78% of the comparator's costs were considered versus 96% for beti-cel and only 44% of the efficacy gain between the two strategies was captured. Based on a collective perspective, recommended by the authorities, the evaluation does not consider all the beneficial long-term and collective effects for the society. Indeed, with a societal perspective, the ICER decreases by 99%.

CONCLUSIONS : Relative to goal of reducing uncertainty, in actuality most costs and effects were not captured in the HAS-type evaluation. Limiting time horizon and not considering a societal perspective had significant impacts. Such results are not representative of benefits of gene therapies in real life. It is therefore necessary for health authorities to adapt health-economic evaluation’s framework for gene therapies so that these evaluations can support more realistic public decisions.