A dose-optimization trial of laronidase (Aldurazyme (R)) in patients with mucopolysaccharidosis I

A dose-optimization trial of laronidase (Aldurazyme (R)) in patients with mucopolysaccharidosis I

Author Giugliani, Roberto Google Scholar
Rojas, Veronica Munoz Google Scholar
Martins, Ana Maria Autor UNIFESP Google Scholar
Valadares, Eugnia R. Google Scholar
Clarke, Joe T. R. Google Scholar
Goes, Jose E. C. Google Scholar
Kakkis, Emil D. Google Scholar
Worden, Mary Alice Google Scholar
Sidman, Marisa Google Scholar
Cox, Gerald F. Google Scholar
Institution Univ Fed Rio Grande do Sul
Universidade Federal de São Paulo (UNIFESP)
Universidade Federal de Minas Gerais (UFMG)
Hosp Sick Children
Hosp Infantil Joana de Gusmao
BioMarin Pharmaceut Inc
Genzyme Corp
Harvard Univ
Abstract Recombinant human alpha-L-iduronidase (Aldurazyme (R) laronidase) is approved as an enzyme replacement therapy to treat the lysosomal storage disorder, mucopolysaccharidosis type I (MPS I) at a dose of 0.58 mg/kg by once-weekly intravenous infusion. To assess whether alternate dosing regimens might provide a better reduction in lysosomal storage, a 26-week, randomized, open-label, multinational dose-optimization trial was conducted. the pharmacodynamic effect and safety of the approved laronidase dose was compared to three alternative regimens (1.2 mg/kg every 2 weeks; 1.2 mg/kg every week; 1.8 mg/kg every 2 weeks) among 33 MPS I patients. the four treatment regimens showed no significant differences in the reduction of urinary glycosaminoglycan excretion or liver volume. Laronidase had an acceptable safety profile in all dose regimen groups. Infusion-associated reactions were the most common drug-related adverse events across dose regimens (by patient incidence), and included pyrexia (21%), vomiting (15%), rash (15%), and urticaria (12%). Patients in the approved dose group had the lowest incidence of drug-related adverse events (38% vs. 63-75%) and infusion-associated reactions (25% vs. 25-63%). There was one death: a patient with acute bronchitis died of respiratory failure 6h after completing the first laronidase infusion. the approved 0.58 mg/kg/week laronidase dose regimen provided near-maximal reductions in glycosaminoglycan storage and the best benefit-to-risk ratio. the 1.2 mg/kg every 2 weeks regimen may be an acceptable alternative for patients with difficulty receiving weekly infusions, but the long-term effects of this regimen are unknown. (C) 2008 Elsevier Inc. All rights reserved.
Keywords Mucopolysaccharidosis (MPS) type I
Hurler
Hurler-Scheie
Scheie
Laronidase
Clinical trial
Dose-optimization
Glycosaminoglycans
Enzyme replacement therapy
Language English
Sponsor BioMarin Pharmaceutical Inc.
Genzyme Corporation
Date 2009-01-01
Published in Molecular Genetics and Metabolism. San Diego: Academic Press Inc Elsevier Science, v. 96, n. 1, p. 13-19, 2009.
ISSN 1096-7192 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 13-19
Origin http://dx.doi.org/10.1016/j.ymgme.2008.10.009
Access rights Closed access
Type Article
Web of Science ID WOS:000262731900003
URI http://repositorio.unifesp.br/handle/11600/31173

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