Since 2013, the coverage of innovative and expensive drugs by the French National Health Insurance considers cost-effectiveness and budget impact, as assessed by the National Authority for Health (HAS) on the basis of an evaluation submitted by the firm. First CAR-T cell therapies were subject to economic evaluation in 2019 in France. We aim at describing the process and results of the economic evaluation of tisagenlecleucel and axicabtagene ciloleucel and the challenges these evaluations raised.

Primary evaluations were submitted by the firms to be reviewed by HAS. The final analyses were submitted to the Committee of Economic Evaluation and Public Health (CEESP), composed of independent economists, clinicians and patients’ representatives. The CEESP issued Opinions related to i) the methodological quality of economic evidence and ii) the cost-effectiveness and budget impact of the drugs under review.

The estimated incremental cost-utility ratio (ICUR) of tisagenlecleucel were rejected, being based on insufficient clinical evidence to estimate and extrapolate the long-term progression and to compare tisagenlecleucel with alternatives. Thus, the CEESP concluded that tisagenlecleucel was not proved cost-effective. The estimated ICUR of axicabtagene ciloleucel at 114,509EUR/QALY vs. chemotherapies was associated with an acceptable level of evidence despite being based on a frail indirect comparison and limited data on quality of life. In a context where France has no official cost-effectiveness threshold, the CEESP considered axicabtagene ciloleucel ICUR to be “very high” and questioned the collective acceptability of the claimed price.

The CEESP stressed that the main source of uncertainty surrounding the ICUR estimates of both drugs was related to the lack of hindsight on effectiveness, especially in terms of overall survival and safety.

The economic evaluation of CAR-T cell therapies highlights the sources of uncertainty underlying the decision and the risk of inefficient resource allocation driven by limited clinical data. It calls for payment schemes accounting for the uncertainty, and effective collection of relevant post-marketing data.