Original ArticlesEnzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human α-L-iduronidase (laronidase)☆
Section snippets
Study Design
The study objective was to confirm the efficacy and safety of laronidase (Aldurazyme, BioMarin Pharmaceutical Inc, Novato, Calif, and Genzyme Corporation, Cambridge, Mass) in patients with MPS I. A randomized, double-blinded, placebo-controlled, 5-center multinational study design was used. After an up to 2-week evaluation phase, patients fulfilling entry criteria underwent random assignment into a 26-week treatment phase with laronidase or placebo. Patients completing the double-blinded study
Results
Of 47 patients enrolled, 2 were excluded because of inability to perform a reproducible FVC maneuver. Of the remaining 45 patients, 22 were randomly assigned to laronidase and 23 to placebo. All 45 patients completed the study and were included in efficacy and safety evaluations. Patients classified as having intermediate disease severity (Hurler-Scheie) comprised 82% and pediatric patients (≤18 years of age) 73% of the study population (Table I). Mean age was 15.5 ± 8.0 years, mean time since
Discussion
This randomized, double-blinded, placebo-controlled, multinational study confirms that laronidase therapy is effective and safe for patients with MPS I. Within only 26 weeks, significant reduction in GAG substrate by laronidase translated into clinically important improvements in respiratory function (FVC and AHI) and physical capacity (6MWT and shoulder flexion). The treatment effect in FVC achieved statistical significance in both prospective analyses, whereas the treatment effect in the 6MWT
Acknowledgements
We gratefully acknowledge the inspiration and cooperation of the study patients and their families and the expert assistance of the study site subinvestigators and coordinators (Maureen Cleary, MD, Elly Hetty, MD, Gustavo Charria, MD, Michele Ford, Frank Bähner, MD, Elke Miebach, MD, Diane Towle, RN, Muge Calikoglu, MD, and Shawn McCandless, MD) and Kevin Barry, Jane McNamara Solomon, RN, Margot Goossens, Susan Richards, PhD, Alison Skrinar, MS, MPH, Gillian Shepard, MD, and Katherine Sims, MD.
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Supported in part by grant RR000046 from the General Clinical Research Centers Program, Division of Research Resources, National Institutes of Health, and by BioMarin/Genzyme LLC.