Indirect Treatment Comparison (ITC) of Avalglucosidase Alfa (AVA) vs Cipaglucosidase Alfa Plus Miglustat (Cipa+mig) in Late-Onset Pompe Disease (LOPD): An Updated Analysis Using Mixed-Model Repeated Measures (MMRM) Data
Author(s)
Roberts ME1, Proskorovsky I2, Shukla P3, O’Callaghan L4, Rawat NS5, Guyot P6, Pollissard L6, Pulikottil Jacob R7
1Neurology, Salford Royal NHS Foundation Trust, Salford, Manchester, UK, 2Evidera, St-Laurent, QC, Canada, 3Evidera, a part of Thermo Fisher Scientific, London, LON, UK, 4Sanofi, Cambridge, MA, USA, 5Sanofi, Hyderabad, Telangana, India, 6Sanofi, Gentilly, France, 7Sanofi, Guildford, UK
Presentation Documents
OBJECTIVES: A previous ITC (Roberts M et al. Value Health 2023;26(6);S37–S38) evaluated the comparative efficacy of AVA vs Cipa+mig in patients with LOPD using simulated treatment comparison (STC) of COMET trial (NCT02782741) data vs PROPEL trial (NCT03729362) data. This ITC demonstrated more favorable outcomes with AVA. The previous ITC used COMET data derived using MMRM methods, and PROPEL data was derived using ANCOVA methods based on the data available then. The current study reports comparative efficacy using MMRM estimates obtained from both trials.
METHODS: The analysis of enzyme replacement therapy (ERT)-naïve patients used individual patient data (IPD) from the Phase 3 COMET trial (AVA, n=51; alglucosidase alfa, n=49) and aggregate data from the Phase 3 PROPEL trial (Cipa+mig, n=27). The analysis of ERT-experienced patients compared IPD from the COMET open-label extension and NEO-1 (NCT01898364)/NEO-EXT (NCT02032524) studies (AVA, n=59) vs aggregate data from the PROPEL and ATB200-02 (NCT02675465, Cohorts I and IV) studies (Cipa+mig, n=81). Changes from baseline (CFB) at Weeks 49–52 were compared for forced vital capacity percent predicted (FVCpp) and 6-minute walk test (6MWT).
RESULTS: Estimated treatment differences (CFB) for AVA vs Cipa+mig in the ERT-naïve population were 5.49% (95% confidence interval [CI]: −0.87, 11.86; p<0.09) for FVCpp and 57.08 meters (CI: 11.04, 103.12; p<0.02) for 6MWT. In the ERT-experienced, the mean difference in FVCpp and 6MWT favored AVA (1.40% and 18.85 meters, respectively). However, CIs were not estimated for the ERT-experienced population as the PROPEL trial results did not report standard errors for MMRM analyses.
CONCLUSIONS: Using the same MMRM analysis across different data sources, AVA demonstrated favorable respiratory function and mobility outcomes in patients with LOPD. The data are consistent and more favorable for AVA compared to the previous ITC analyses, with statistically significant results in treatment-naïve patients, and further support the comparative efficacy of AVA vs Cipa+mig.
Conference/Value in Health Info
Value in Health, Volume 27, Issue 12, S2 (December 2024)
Code
CO118
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Musculoskeletal Disorders (Arthritis, Bone Disorders, Osteoporosis, Other Musculoskeletal), Rare & Orphan Diseases, Respiratory-Related Disorders (Allergy, Asthma, Smoking, Other Respiratory)