Galsulfase (Naglazyme®) therapy in infants with mucopolysaccharidosis VI

Abstract

ObjectiveTo evaluate the efficacy and safety of two dose levels of galsulfase (Naglazyme®) in infants with MPS VI.Study designThis 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.ResultsFour 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.ConclusionsGalsulfase 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-013-9654-7) contains supplementary material, which is available to authorized users.

Therapies for the bone in mucopolysaccharidoses

“…Aggregated data from patients who had initiated ERT when less than 5 years of age showed that over 50% of patients were below the 3rd percentile for height, although one girl was above the 97th percentile. Comparing baseline height prior to initiation of ERT to height at the end of the study, 37.5% patients remained on the same percentile growth curve, 9.4% improved to a percentile curve above and 53% fell below their original percentile curve, suggesting that growth is not normalized by ERT [63][64][65].…”

Therapies for the bone in mucopolysaccharidoses

“…Aggregated data from patients who had initiated ERT when less than 5 years of age showed that over 50% of patients were below the 3rd percentile for height, although one girl was above the 97th percentile. Comparing baseline height prior to initiation of ERT to height at the end of the study, 37.5% patients remained on the same percentile growth curve, 9.4% improved to a percentile curve above and 53% fell below their original percentile curve, suggesting that growth is not normalized by ERT [63-65]. …”

Targeted delivery of acid alpha-glucosidase corrects skeletal muscle phenotypes in Pompe disease mice

“…ERT for other lysosomal diseases, such as rGALNS for mucopolysaccharidosis VIA 34 and rARSB for mucopolysaccharidosis VI 35 , also have poor delivery to diseased non-CNS organs partially due to the limitations of CI-MPR 36 . Enzyme delivery to address the skeletal phenotypes in mucopolysaccharidoses I-VII remains a challenge due to the virtually nonexistent delivery to these tissues 37 .…”