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.
Bibliographical noteFunding Information:
The clinical study was sponsored by BioMarin Pharmaceutical Inc (BioMarin). As the study sponsor, BioMarin was responsible for the design of the study and analysis of data and provided assistance with writing this report. This article reports the results of a clinical trial (registered at www.clinicaltrials.gov; NCT00299000). Authors not employed by the sponsor confirm independence from the study sponsor and their contributions were not influenced by the sponsor.
This study was supported, in part, with funds provided by the NIH CTSA grant UL1 RR0241315 (P. R. Harmatz). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conflicts of interest P. R. Harmatz, N. Guffon, L. M. Randolph, E. Braunlin, and R. S. Lachman have provided consulting services to BioMarin Pharmaceutical Inc (BioMarin). P. R. Harmatz has received research grants, participated in advisory boards, and received speakers honoraria and travel support from BioMarin. P. Garcia has received travel support from BioMarin. L. M. Randolph has received research funding from BioMarin. E. Braunlin has participated in advisory boards and received speakers honoraria and travel support from BioMarin. R. Shediac and C. Decker are employees and stockholders of BioMarin Pharmaceutical Inc.