Galsulfase (Naglazyme)

Galsulfase is a recombinant enzyme-replacement drug for mucopolysaccharidosis type VI (MPS VI, or Maroteaux-Lamy syndrome), a rare inherited disorder in which a missing enzyme lets sugar molecules accumulate throughout connective tissue, bone and organs while — unlike several other MPS diseases covered on this site — typically sparing intelligence entirely. Approved in 2005 as the first disease-specific treatment for MPS VI anywhere, it was studied only in patients aged 5 and older at approval; a dedicated infant trial published nearly a decade later extended real safety and dosing evidence down to children as young as three months, closing a real evidence gap for the disease's earliest-treatable patients.

A third MPS disease, a third missing enzyme

Mucopolysaccharidosis type VI (MPS VI, or Maroteaux-Lamy syndrome) is a rare inherited disorder caused by deficient activity of N-acetylgalactosamine 4-sulfatase, also called arylsulfatase B — a different enzyme again from the ones missing in the MPS I, MPS II and MPS IVA diseases covered elsewhere on this site (see this site's laronidase, idursulfase and elosulfase alfa pages), though all four break down overlapping glycosaminoglycans and produce overlapping physical features. Without functioning arylsulfatase B, dermatan sulfate accumulates throughout connective tissue, bone, heart valves, the airway and the cornea, producing short stature, joint stiffness, coarsened facial features, corneal clouding, cardiac valve disease, and — in its most severe form — a shortened lifespan from cardiopulmonary complications. Unlike the neuronopathic forms of MPS I and MPS II, MPS VI does not typically affect intelligence. Published birth-prevalence estimates vary by population, roughly from 1 in 240,000 to 1 in 320,000, making it, like the other diseases in this cluster, ultra-rare. Before 2005, no disease-specific drug existed for MPS VI. BioMarin Pharmaceutical developed recombinant human arylsulfatase B (galsulfase), and the FDA approved it on 31 May 2005 under the brand name Naglazyme — the first treatment specifically for MPS VI approved anywhere, granted seven years of orphan-drug market exclusivity.

The trial that won approval

The pivotal evidence was a randomized, double-blind, placebo-controlled, multinational trial of 39 patients with MPS VI, aged 5 to 29, weighing between 14 and 47 kilograms. Patients received either galsulfase 1 mg/kg or placebo by weekly infusion for 24 weeks, with the primary efficacy measure being distance walked in a 12-minute walk test (12MWT) and a key secondary measure being the number of stairs climbed per minute in a 3-minute stair-climb test (3MSC). After 24 weeks, galsulfase-treated patients walked a mean 92 meters further in the 12MWT than the placebo group (P=.025) — a real, statistically significant primary-endpoint result — alongside a mean 5.7 more stairs climbed per minute on the secondary 3MSC measure, which narrowly missed conventional statistical significance (P=.053), plus significant reductions in urinary glycosaminoglycan excretion (Harmatz P, Whitley CB, Waber L, Pais R, Steiner R, Plecko B, et al., "Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study," J Pediatr 2006;148(4):533-539, PMID 16647419).¹ A clearly significant primary endpoint, alongside a secondary measure trending the same direction without quite clearing the conventional threshold, supported full FDA approval rather than an accelerated pathway — the same kind of "real effect, imperfect statistics on every single measure" pattern that recurs across several enzyme-replacement trials covered on this site.

Extending the evidence down to infancy

Naglazyme's original approval rested on a trial enrolling patients aged 5 and older, leaving a real evidence gap for infants and very young children — exactly the population in whom starting enzyme replacement earliest might matter most, before irreversible skeletal and cardiac damage accumulates. BioMarin later ran a dedicated, open-label Phase 4 study in four infants aged 3 months to just under 13 months, treated with either 1 mg/kg or 2 mg/kg of galsulfase weekly for at least 52 weeks (Harmatz P, Mengel KE, Giugliani R, Valayannopoulos V, Lin SP, Parini R, et al., "Enzyme replacement therapy in patients with mucopolysaccharidosis VI: A phase 4 study with galsulfase (Naglazyme^®) in infants," J Inherit Metab Dis 2014;37(2):277-287). The infants' safety profile was consistent with what had already been seen in the original 5-to-29-year-old trial population, supporting the drug's use in younger children rather than confining it to patients old enough to have enrolled in the pivotal trial. This is a narrower, less dramatic story than the shortage and manufacturing failures that run through several of this site's other enzyme-replacement pages — a real, purpose-built follow-on study quietly closing a genuine age gap in the original evidence, rather than a regulatory setback of any kind.

A shared risk across every MPS enzyme drug on this site: anaphylaxis

Like laronidase, idursulfase and elosulfase alfa, Naglazyme carries an FDA boxed warning for life-threatening hypersensitivity reactions, including anaphylaxis, which can occur during an infusion or up to 24 hours afterward, in patients receiving their very first dose or after months of prior tolerance. The FDA-approved label requires administering the drug in a setting with ready access to cardiopulmonary resuscitation equipment and appropriate emergency medications, including epinephrine, and calls for permanent discontinuation if a severe reaction occurs. This is not a quirk specific to Naglazyme — it is close to a defining feature of infused recombinant enzyme-replacement therapy as a drug class, repeated with only minor wording differences across every MPS enzyme page on this site.

Current status

Naglazyme remains FDA-approved and currently marketed by BioMarin in the US, EU and other markets, and remains the only FDA-approved disease-specific treatment for MPS VI. It is a core, growing part of BioMarin's enzyme-therapies business: the company reported $130.1 million in Naglazyme revenue in the first quarter of 2026 alone, up from $114.3 million in the same quarter of 2025. At its approved weight-based dose of 1 mg/kg weekly and current list pricing, published cost-effectiveness reviews have estimated a full year of treatment at roughly $223,000 for a smaller child up to $750,000 for a larger adolescent or adult — a direct consequence of dosing that scales with body weight rather than a flat annual price. No FDA-approved generic, biosimilar or competing disease-specific therapy for MPS VI exists as of 2026.