Health State Utility Values in Fabry Disease: Insights from the Pegunigalsidase Alfa Clinical Trials.

Introduction: Fabry disease (FD) is a rare lysosomal storage disorder that is associated with pain and progressive damage to the renal, cardiac, and cerebrovascular systems. Enzyme replacement therapy (ERT) is one of the treatment options for FD and the most recently approved ERT agent, pegunigalsidase alfa, has shown clinical efficacy in three phase 3 clinical trials of adults with FD: BALANCE, BRIDGE, and BRIGHT. Recent published guidelines support the mapping of health utility state data to the EuroQol-5 Dimension-3 Level (EQ-5D-3L) index to align with the preferred methodology used by the National Institute for Health and Care Excellence (NICE). Therefore, the primary objective of this study was to estimate EQ-5D-3L values in clinical trials of pegunigalsidase alfa for FD for future cost-utility analyses.

Methods: A mixed effects model was developed to predict values derived from EQ-5D-3L for the following health states used in cost-utility analyses: no Fabry clinical event (FCE)/no pain-related adverse event (AE), pain-related AE, cardiac FCE, cerebrovascular FCE, and renal FCE.

Results: The baseline EQ-5D-3L utility value had a statistically significant (p < 0.0001) impact on utility values, whereas study, age, sex, disease type, treatment arm, kidney function, and serious AE were not statistically significant. Health state utility values with 95% confidence intervals (CI) for the final model were as follows: no FCE/no pain-related AE, 0.8005 (0.7675, 0.8334); pain-related AE, 0.7737 (0.7262, 0.8211); cardiac FCE, 0.7189 (0.6274, 0.8103); cerebrovascular FCE, 0.7923 (0.6633, 0.9212); and renal FCE, 0.6881 (0.3887, 0.9874).

Conclusions: The utility values generated by the present study are generally in line with EQ-5D values in the FD literature and can be used to inform both economic evaluations and our understanding of the impact that FD has on quality of life.

Trial Registration: NCT03018730, NCT02795676, NCT03180840.