Evaluation of galsulfase for the treatment of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)

Abstract

Introduction: Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive lysosomal storage disorder caused by a deficiency in the lysosomal enzyme N-acetylgalactosamine 4-sulfatase (arylsulfatase B), leading to an accumulation of glycosaminoglycans within lysosomes. MPS VI patients experience a progressive, chronic and multisystemic disease that causes not only significant morbidity but also early mortality. Areas covered: Galsulfase, a recombinant human N-acetylgalactosamine 4-sulfatase, rhASB (Naglazyme Ò), is produced by recombinant DNA technology in a CHO-derived cell line, and was approved in the US (2005) and the EU (2006) for use in MPS VI patients. The authors examine the published pharmacokinetic, safety and efficacy data from the Phase I/II, Phase III, Phase III extension, post-marketing surveillance studies of galsulfase, published case reports and cohort of patients treated with rhASB. Expert opinion: Galsulfase is generally well tolerated, having an acceptable safety profile. Few infusion reactions have occurred during administration of galsulfase, being generally mild-to-moderate in severity. Improvements in 12-minute walk test, nearly significant improvement in 3-min stair climb and significant reduction in urinary GAG levels were demonstrated in the 24-week, randomized, double-blind Phase III trial that led to the approval of the drug. As in other lysosomal storage diseases, the antibody response to enzyme replacement therapy can differ greatly between patients and may to some extent relate to the genotype. Nevertheless, antibody formation seems to have little impact on clinical outcome in MPS VI patients treated with galsulfase.

Enzymes Approved for Human Therapy: Indications, Mechanisms and Adverse Effects

“…Elosulfase alfa, a CHO cell-derived recombinant form of N-acetylgalactosamine-6-sulfatase [52] (Tables 1, 2), was granted marketing approval by the FDA and the EMA in 2014 [53,54] for the treatment of patients with MPS IVA, also known as Morquio A syndrome, an autosomal recessive disorder caused by a deficiency of the enzyme [55]. In 2005, galsulfase, a recombinant form of N-acetylgalactosamine-4-sulfatase (Tables 1, 2), was approved by the FDA for the treatment of patients with MPS VI (Maroteaux-Lamy syndrome), an autosomal recessive disease due to deficiency of N-acetylgalactosamine-4-sulfatase [56][57][58]. Although ERT with galsulfase has been relatively successful in treating some aspects of MPS VI disease, such as growth, puberty, and pulmonary function, it has been disappointing in alleviating joint, ophthalmic, and CNS symptoms.…”

“…Although ERT with galsulfase has been relatively successful in treating some aspects of MPS VI disease, such as growth, puberty, and pulmonary function, it has been disappointing in alleviating joint, ophthalmic, and CNS symptoms. Starting treatment at an earlier age may be beneficial for growth, and some aspects of the syndrome may be modified by longer periods of treatment [58].…”

Fifteen years of enzyme replacement therapy for mucopolysaccharidosis type VI (Maroteaux–Lamy syndrome): a case report

“…Joint mobility is worse with increasing patient age. Thus, evaluation of mobility of the knees, hip, and elbows are considered a good marker of MPS VI evolution [ 13 , 14 ]. Thoracolumbar kyphosis and oval vertebral bodies with inferior protrusion can also be verified in patients with MPS VI [ 13 ].…”

“…Thus, evaluation of mobility of the knees, hip, and elbows are considered a good marker of MPS VI evolution [ 13 , 14 ]. Thoracolumbar kyphosis and oval vertebral bodies with inferior protrusion can also be verified in patients with MPS VI [ 13 ]. Wrists and hands may be affected by the enlargement and shortening of the metacarpals and phalanges, leading to flexure contracture of the fingers and a claw-hand aspect [ 1 , 12 ].…”

“…Hematopoietic stem cell transplantation (HSCT) became a therapeutic alternative to counteract the disease progression but is associated with a high risk of morbidity and mortality. The advent of enzyme replacement therapy (ERT), available since 2005, constituted a significant improvement in terms of therapy, changing the natural history of this illness [ 13 ]. The objective of this study is to report the clinical history of a patient with MPS VI treated with ERT for 15 years.…”