The cost-effectiveness of enzyme replacement therapies versus best supportive care for treating late onset Pompe disease in the UK NHS.

OBJECTIVE

To assess the cost-effectiveness of enzyme replacement therapy (ERT) compared with best supportive care (BSC) for late-onset Pompe disease (LOPD) in a UK NHS setting.

METHODS

A discrete event simulation model was developed using data from a Bayesian network meta-analysis, trials and extension studies, and long-term observational cohorts. Costings were derived from NICE assessments of LOPD treatments. Disease progression was modelled using forced vital capacity (FVC) % predicted and six-minute walk distance (6MWD).

RESULTS

ERT was associated with an incremental cost of £3.26 million and 1.64 additional QALYs compared to BSC, yielding an incremental cost-effectiveness ratio (ICER) of £2 million per QALY gained, and generating a net health effect (NHE) exceeding -100 QALYs per treated patient. Scenario analyses confirmed that ERT remained cost-ineffective under all plausible assumptions. Discounts of ~ 92.3% and ~ 89% on the list price of ERT would be required to achieve cost-effectiveness at thresholds of £30,000 and £100,000 per QALY gained, respectively.

CONCLUSIONS

While ERT provides modest long-term health benefits relative to BSC, it is structurally highly cost-ineffective, generating substantial negative NHE for the NHS population, even under the most optimistic assumptions. These results are primarily driven by very high acquisition costs of ERT. The historic commissioning of ERT without reference to the UK’s value-based pricing framework has significantly impacted NHS spending and distorted NICE decision-making. Without reform to the appraisal process, the NHS faces affordability challenges that may hinder access to innovative therapies and result in recommendations that displace more health than they generate.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10198-025-01868-2.