Long-term enzyme replacement therapy: Findings from the mucopolysaccharidosis VI clinical surveillance program after 15 years follow-up
- PMID: 40381595
- DOI: 10.1016/j.ymgme.2025.109135
Long-term enzyme replacement therapy: Findings from the mucopolysaccharidosis VI clinical surveillance program after 15 years follow-up
Abstract
Objective: To evaluate the long-term real-world efficacy and safety of galsulfase enzyme replacement therapy (ERT) in patients enrolled in the mucopolysaccharidosis (MPS) VI Clinical Surveillance Program (CSP).
Methods: The CSP collected long-term observational data of routine clinical and laboratory assessments from 30 June 2005 to 01 May 2020. Outcomes included urinary glycosaminoglycan (uGAG) level, 6-min walk test (6MWT), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), anthropometrics and adverse events.
Results: The final analysis population included 221 participants with MPS VI; 212 participants received ERT (median ERT exposure time 11.7 years). In ERT-treated participants with both baseline and follow-up data, uGAG levels decreased by a mean of 59.7 % after a mean follow-up of 8.0 years (P < 0.0001; n = 84), 6MWT distance increased by a mean (SE) of 42.3 (21.81) meters after a mean follow-up of 7.0 years (P = 0.0610, n = 35), FEV1 increased by 0.36 (0.098) L after 6.5 years (P = 0.0014, n = 24), and FVC increased by 0.52 (0.143) L after 6.3 years (P = 0.0013, n = 25). Improvements were seen across subgroups of participants with high and low baseline uGAG levels (>200 and ≤ 200 μg/mg creatinine). 6MWT and pulmonary function increased primarily in participants younger than 18 years at baseline while older patients showed stabilization. Galsulfase was generally well tolerated with no new safety signals identified. Most adverse events were MPS-related clinical manifestations and considered not related to galsulfase by investigators.
Conclusions: Data collected in the CSP over 15 years provide real-world evidence for sustained improvements in endurance and pulmonary function among patients with MPS VI treated with ERT, with no new safety concerns identified. These results further support and confirm observations from the clinical trials and previous findings from the CSP.
Keywords: Enzyme replacement therapy; Galsulfase; Long-term; Maroteaux-Lamy syndrome; Mucopolysaccharidosis VI; Registry.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest Barbara K Burton received consulting fees and speaker or lecture fees from BioMarin related to subject matter but not to the manuscript. She has no other conflicts in past three years related to the subject matter. Paul R Harmatz has provided consulting support to and/or has received grant support from Adrenas, Allievex, ASPA, Azafros, BioMarin, Bridgebio, Calcilytics, Chiesi, Denali, GC Pharma, Grace Science, Idorsia, JCR, Neurogene, Novel Pharma, Orchard Therapeutics, Orphazyme, QED, Rallybio, RegenXbio, Sangamo, Shire, and Takeda in the last three years. Christina Lampe has received honoraria for medical advice, speakers fees, and travel support from Amicus, Alexion, BioMarin, Chiesi, Kyowa Kirin, Regenxbio, Sanofi, and Takeda. Rossella Parini received travel reimbursements and consultation fees from Sanofi in the last two years. Reena Sharma has no conflicts of interest. Elisa Leão Teles received research grants (as per clinical trials hospital contracts), travel reimbursement, consultation and advisory fees, and speaking fees from BioMarin, Chiesi, Sanofi Genzyme, and Ultragenix in the last three years. Veronika Horvathova and Alice Lail are employees of BioMarin.
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