OBJECTIVES: In May 2024, the UK’s National Institute for Health and Care Excellence (NICE) concluded exagamglogene autotemcel (exa‑cel) for sickle cell disease (SCD) was unlikely to be cost‑effective. Conventional cost‑effectiveness analysis (CEA) approaches, however, do not account for disease severity, uncertainty in outcomes, and patient risk preferences for quality of life (QoL), which can result in a mis-estimate of treatment value. To address this concern, we applied two adjustment methods to a similar CEA on exa‑cel, conducted by the US Institute for Clinical and Economic Review (US-ICER) in 2023, and adjusted to the UK setting.

METHODS: As NICE’s CEA results for exa-cel are not available, we converted US-ICER CEA results to the UK setting using purchasing power parities and applied two adjustment‑methods: 1) the Quality Adjusted Life Year (QALY) Shortfall method to account for the high severity of SCD and 2) the Generalized Risk‑Adjusted Cost Effectiveness (GRACE) framework to modify the CEA results to additionally account for treatment effectiveness and trade-offs between life expectancy and QoL, and to consider an alternative willingness to pay (WTP) threshold.

RESULTS: The base case results of the unadjusted CEA indicated the incremental cost‑effectiveness ratio (ICER) for exa‑cel for SCD in the UK is £160K per QALY gained. After adjusting these results by a weight of 1.2 for an absolute QALY Shortfall of 13.2 in SCD, the ICER is £133K. When adjusting the base case results with the GRACE method, the ICER drops to £151K and the recommended WTP threshold reflecting rare diseases is £151K/QALY rather than £100k/QALY.

CONCLUSIONS: Our results show both the QALY shortfall and GRACE methods would improve the cost-effectiveness of exa-cel. In addition, our analysis shows the GRACE method would raise the WTP threshold, which, in the scenario presented, would alter the conclusion and recommendation on the cost‑effectiveness of exa‑cel.