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Galsulfase (Naglazyme®) therapy in infants with mucopolysaccharidosis VI
Author(s) -
Harmatz Paul R.,
Garcia Paula,
Guffon Nathalie,
Randolph Linda M.,
Shediac Renée,
Braunlin Elizabeth,
Lachman Ralph S.,
Decker Celeste
Publication year - 2014
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-013-9654-7
Subject(s) - medicine , adverse effect , creatinine , mucopolysaccharidosis , renal function , urinary system , pediatrics , gastroenterology , urology , surgery
Objective To evaluate the efficacy and safety of two dose levels of galsulfase (Naglazyme®) in infants with MPS VI. Study design This was a phase 4, multicenter, multinational, open‐label, two‐dose level study. Subjects were randomized 1:1 to receive weekly infusions of 1.0 or 2.0 mg/kg of galsulfase for a minimum of 52 weeks. Progression of skeletal dysplasia was determined by monitoring physical appearance, radiographic changes, and growth. Urinary glycosaminoglycan (GAG) levels, gross and fine motor function, cardiac function, vision, hearing, and health resource utilization were evaluated. Safety assessments were performed. Results Four infants (aged 3.3–12.7 months) participated in the study. Galsulfase was well tolerated at 1.0 and 2.0 mg/kg/week dose levels with no drug‐related serious adverse events. Two subjects experienced a total of four possible treatment‐related adverse events which were all considered mild. Length and weight remained within age‐expected norms. Skeletal abnormalities continued to progress in all subjects. High baseline urinary GAG levels (mean: 870 μg/mg creatinine) decreased by approximately 70 %; these reduced levels were maintained (mean: 220 μg/mg creatinine at week 52) despite the development of anti‐galsulfase antibodies. Hearing, cardiac function, hepatosplenomegaly, and facial dysmorphism stabilized or improved, but corneal clouding progressed. There was no clear difference in safety or efficacy between the two doses. Conclusions Galsulfase at two dose levels was safe and well tolerated in infants. Normal growth was maintained but skeletal abnormalities continued to progress. Urinary GAG levels decreased with treatment. Early initiation of galsulfase may prevent or slow progression of some disease manifestations.