Late-Onset Pompe Disease (LOPD) Patients Treated with Avalglucosidase Alfa Show Favorable Results Compared to Cipaglucosidase Alfa Plus Miglustat: Indirect Treatment Comparison


Roberts M1, Proskorovsky I2, Guyot P3, Shukla P2, Periquet M4, Thibault N5, Hamed A5, Riou França L3, Pollissard L3
1Salford Royal NHS Foundation Trust, Salford, UK, 2Evidera, St-Laurent, QC, Canada, 3Sanofi, Chilly-Mazarin, France, 4Sanofi, Berlin, Germany, 5Sanofi, Cambridge, MA, USA

Presentation Documents

OBJECTIVES: There have been no head-to-head studies comparing avalglucosidase alfa (AVA), approved in multiple countries worldwide, and cipaglucosidase alfa plus migulstat (Cipa+mig), which is currently under review by health authorities. A recent indirect treatment comparison (ITC) by Fu et al. included single-arm studies into an anchored network of randomized controlled trials (RCT) and produced incoherent results that contradict direct evidence from both COMET and PROPEL phase 3 studies. Our study aimed to estimate the relative efficacy of AVA vs. Cipa+mig in LOPD patients using ITC with robust methodology.

METHODS: Anchored and un-anchored simulated treatment comparisons (STCs) were conducted, adjusting for differences in prognostic factors and treatment effect modifiers. Enzyme replacement therapy (ERT)-naive patient analyses used data from COMET (NCT02782741) (AVA, n=51 and alglucosidase alfa [ALGLU], n=49) and PROPEL (NCT03729362) (Cipa+mig, n=20 and [ALGLU], n=7). ERT-experienced patient analyses used AVA data (n=59) from COMET-OLE (open-label-extension) and NEO-1 (NCT01898364)/EXT (NCT02032524), and Cipa+mig data (n=81) from PROPEL plus ATB20002 (cohorts I and IV). Changes from baseline at week 52 in forced vital capacity percent predicted (FVCpp), maximal inspiratory pressure (MIPpp), maximal expiratory pressure (MEPpp), and 6-minute walk test (6MWT) (meters) were compared.

RESULTS: In ERT-naive patients, AVA was favorable vs. Cipa+mig for FVCpp (4.69; 95% confidence interval (CI): [−3.22, 12.61]), MIPpp (1.29; [−27.38, 29.96]), MEPpp (2.32; [−24.75, 29.4]) and 6MWT (41.88; [−5.46, 89.22]). In ERT-experienced patients, AVA was favorable vs. Cipa+mig for FVCpp (1.16; [−1.88, 4.19]), MIPpp (4.24; [−4.93, 13.41]), and 6MWT (7.67; [−21.67, 37.02]), with a statistically significant MEPpp result (8.62; [0.02, 17.21]).

CONCLUSIONS: Our STCs suggest better outcomes with AVA vs. Cipa+mig. STCs’ strength lies in using the best methodology for each subpopulation. The uncertainty of each comparison correctly reflects the available data. Ongoing real-world experience with AVA among ERT-experienced patients from managed access programs and registries will provide additional evidence.

Conference/Value in Health Info

2023-05, ISPOR 2023, Boston, MA, USA

Value in Health, Volume 26, Issue 6, S2 (June 2023)




Clinical Outcomes, Study Approaches

Topic Subcategory

Clinical Outcomes Assessment, Comparative Effectiveness or Efficacy, Meta-Analysis & Indirect Comparisons


Rare & Orphan Diseases, Respiratory-Related Disorders (Allergy, Asthma, Smoking, Other Respiratory)

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