COMPARATIVE EQ-5D-5L UTILITY OUTCOMES ACROSS PEGUNIGALSIDASE ALFA REGIMENS AND AGALSIDASE BETA IN ADULTS WITH FABRY DISEASE
Author(s)
Khashayar Azimpour, MD, PhD1, Irene Koulinska, MD, ScD2, Angie Raad, MSc3, Alberto Vidal Diez, PhD, BSc4.
1Chiesi Canada Corp, Woodbridge, ON, Canada, 2Chiesi USA, Inc., Boston, MA, USA, 3Cytel, Toronto, ON, Canada, 4Cytel, Madrid, Spain.
1Chiesi Canada Corp, Woodbridge, ON, Canada, 2Chiesi USA, Inc., Boston, MA, USA, 3Cytel, Toronto, ON, Canada, 4Cytel, Madrid, Spain.
OBJECTIVES: Fabry disease is a progressive, multisystem disorder that can impair health-related quality of life (HRQoL). Enzyme replacement therapy (ERT) is a key treatment approach. Available ERTs include agalsidase alfa, agalsidase beta, and pegunigalsidase alfa. Pegunigalsidase alfa is approved at 1.0 mg/kg every 2 weeks (E2W), while the 2.0 mg/kg every 4 weeks (E4W) regimen has recently been approved in Europe/UK for patients stable on ERT. This exploratory analysis estimated adjusted EQ-5D-5L utility differences for pegunigalsidase alfa E4W versus agalsidase beta E2W and pegunigalsidase alfa E2W.
METHODS: Individual patient data from BALANCE, a 24-month randomized trial of pegunigalsidase alfa E2W versus agalsidase beta, and BRIGHT (CLI-06657AA1-03) an open-label switch-over study/extension of pegunigalsidase alfa E4W, were harmonized. Cross-trial differences were adjusted using three approaches. DR-OW, the primary analysis, combined logistic propensity score weighting with outcome regression and focused on comparable patients; after weighting, effective sample size (ESS) decreased from 51 to 34 at Week 52 and from 46 to 27 at Week 104 for E4W versus agalsidase beta; corresponding values for E4W versus pegunigalsidase alfa E2W were 73 to 45 and 70 to 35. DR-SIPW, the sensitivity analysis, used a similar propensity score framework; ESS decreased to 11/8 and 18/16. Pooled OLS adjusted for covariates without weighting; therefore, ESS did not decrease.
RESULTS: In DR-OW, pegunigalsidase alfa E4W showed significantly higher EQ-5D-5L utility versus agalsidase beta at week 52 (0.092; p=0.016), with a nonsignificant numerical advantage at Week 104 (0.025; p=0.650). Within pegunigalsidase alfa-treated patients, utilities were similar between regimens, numerically favoring E2W at Week 52 (-0.033; p=0.346) and E4W at Week 104 (0.100; p=0.109). Results were consistent across methods.
CONCLUSIONS: Pegunigalsidase alfa E4W showed a favorable HRQoL profile across comparisons, suggesting potential quality-of-life benefits with less frequent dosing. As a post-hoc analysis, these findings are hypothesis-generating and subject to the limitations of exploratory research.
METHODS: Individual patient data from BALANCE, a 24-month randomized trial of pegunigalsidase alfa E2W versus agalsidase beta, and BRIGHT (CLI-06657AA1-03) an open-label switch-over study/extension of pegunigalsidase alfa E4W, were harmonized. Cross-trial differences were adjusted using three approaches. DR-OW, the primary analysis, combined logistic propensity score weighting with outcome regression and focused on comparable patients; after weighting, effective sample size (ESS) decreased from 51 to 34 at Week 52 and from 46 to 27 at Week 104 for E4W versus agalsidase beta; corresponding values for E4W versus pegunigalsidase alfa E2W were 73 to 45 and 70 to 35. DR-SIPW, the sensitivity analysis, used a similar propensity score framework; ESS decreased to 11/8 and 18/16. Pooled OLS adjusted for covariates without weighting; therefore, ESS did not decrease.
RESULTS: In DR-OW, pegunigalsidase alfa E4W showed significantly higher EQ-5D-5L utility versus agalsidase beta at week 52 (0.092; p=0.016), with a nonsignificant numerical advantage at Week 104 (0.025; p=0.650). Within pegunigalsidase alfa-treated patients, utilities were similar between regimens, numerically favoring E2W at Week 52 (-0.033; p=0.346) and E4W at Week 104 (0.100; p=0.109). Results were consistent across methods.
CONCLUSIONS: Pegunigalsidase alfa E4W showed a favorable HRQoL profile across comparisons, suggesting potential quality-of-life benefits with less frequent dosing. As a post-hoc analysis, these findings are hypothesis-generating and subject to the limitations of exploratory research.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
PCR84
Topic
Patient-Centered Research
Topic Subcategory
Health State Utilities, Patient-reported Outcomes & Quality of Life Outcomes
Disease
Rare & Orphan Diseases