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Updated: Jun 14, 2025
In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease
Published on: December 20, 2017
Long-term enzyme replacement therapy: Findings from the mucopolysaccharidosis VI clinical surveillance program after
Barbara K Burton1, Paul R Harmatz2, Veronika Horvathova3
1Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA; San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy.
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.
