Laronidase (Aldurazyme)

Laronidase is a recombinant enzyme-replacement drug for mucopolysaccharidosis type I (MPS I), a rare inherited disorder in which a missing enzyme lets sugar molecules build up throughout the body, damaging joints, organs and, in its most severe form, the brain. Approved in 2003 as the first disease-specific treatment for MPS I anywhere, it reached the market through an unusual two-company joint venture rather than a single manufacturer developing and selling it alone — and even a unanimous FDA advisory-committee vote in its favor wasn't enough to avoid a further three-month delay over unresolved manufacturing and labeling issues.

A disease with a wide phenotypic range, and no treatment before 2003

Mucopolysaccharidosis type I (MPS I) is a rare inherited disorder caused by deficient activity of alpha-L-iduronidase, an enzyme that normally breaks down two glycosaminoglycans, dermatan sulfate and heparan sulfate. Without it, these partially degraded sugar chains accumulate inside lysosomes throughout the body, producing a wide range of severity depending on how much residual enzyme activity a patient has. At the severe end, Hurler syndrome typically presents before 18 months of age with organ enlargement, skeletal deformity, corneal clouding and progressive cognitive decline, and was historically fatal in childhood; at the mild end, Scheie syndrome causes joint stiffness, corneal clouding and cardiac valve disease but with normal intelligence and a near-normal lifespan; an intermediate Hurler-Scheie form falls between the two. Before 2003, no disease-specific drug existed for any form of MPS I — the only intervention with real disease-modifying evidence was hematopoietic stem cell transplantation, generally reserved for young children with the severe Hurler form because of the transplant's own serious risks, and even that does not reverse skeletal or corneal damage already present.

BioMarin Pharmaceutical, founded in 1997 specifically to develop enzyme-replacement therapies for rare diseases, made recombinant alpha-L-iduronidase (laronidase) its first program, and in September 1998 partnered with Genzyme in a joint venture to fund, develop and commercialize the drug together rather than have BioMarin bring it to market alone — an arrangement described further below. The FDA approved the result on 30 April 2003 under the brand name Aldurazyme, for patients with Hurler and Hurler-Scheie forms of MPS I and for patients with moderate to severe symptoms of the Scheie form — the first disease-specific treatment for MPS I approved anywhere.

The trial that won approval

The pivotal evidence was a randomized, double-blind, placebo-controlled, multinational trial of 45 patients with MPS I, aged 6 to 43 — one with the Hurler form, 37 with Hurler-Scheie, and seven with Scheie, a population weighted toward the disease's more attenuated end, reflecting that severe Hurler patients were more often treated with stem cell transplantation instead. Patients received either laronidase (100 U/kg, roughly 0.58 mg/kg) or placebo by weekly infusion for 26 weeks, with co-primary endpoints of change in percent-predicted forced vital capacity (FVC) and change in six-minute walk test (6MWT) distance. Laronidase-treated patients improved by a mean 5.6 percentage points in percent-predicted FVC over placebo (P=.009) and by a mean 38.1 meters in 6MWT distance (P=.039 by the trial's prospectively planned analysis of covariance), alongside significant reductions in urinary glycosaminoglycan excretion, liver size, and sleep apnea/hypopnea episodes (Wraith JE, Clarke LA, Beck M, Kolodny EH, Pastores GM, Muenzer J, et al., "Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase)," J Pediatr 2004;144(5):581-588, PMID 15126990, DOI: 10.1016/j.jpeds.2004.01.046).¹ That is real, statistically significant improvement across multiple organ systems in a 26-week trial — modest in absolute terms for a chronic, progressive disease, but a genuine departure from a natural history of continuous decline.

A unanimous advisory vote — and a delay anyway

On 15 January 2003, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted unanimously that BioMarin and Genzyme had demonstrated laronidase's efficacy in treating MPS I without serious safety concerns — about as strong an advisory signal as a drug can get. Despite that vote, the FDA did not immediately approve the drug: on 29 January 2003, the companies disclosed that the FDA had issued an approvable letter rather than an outright approval, identifying three outstanding issues to resolve — the content of post-marketing commitments, final product labeling, and completion of the manufacturing-facility inspection process — none of which reopened the efficacy question the advisory committee had already settled. BioMarin and Genzyme resolved those items over the following three months, and the FDA granted full marketing approval on 30 April 2003. The gap between a unanimous advisory vote and final approval is a genuine, if unglamorous, illustration of how FDA review separates a scientific judgment about whether a drug works from the administrative work of confirming it can be manufactured and labeled correctly — a distinction easy to lose sight of in accounts that treat an advisory vote as equivalent to approval itself.

An unusual two-company joint venture

Unlike most of the enzyme-replacement drugs covered elsewhere on this site, Aldurazyme was not simply developed and marketed by a single company. BioMarin Pharmaceutical and Genzyme Corporation organized a formal joint venture, BioMarin/Genzyme LLC, which commenced operations on 4 September 1998 under a collaboration agreement in which both companies funded development costs equally and jointly held a worldwide, exclusive, royalty-free license to develop, manufacture and market the drug through the joint venture; Genzyme separately agreed to pay BioMarin a $12.1 million milestone payment once the FDA approved the drug. Under this original structure the two companies split both the ongoing costs and the eventual profits 50/50. They restructured the arrangement on 1 January 2008, replacing the joint 50/50 cost-and-profit split with a simpler one in which Genzyme records Aldurazyme sales directly and pays BioMarin a tiered royalty of roughly 39.5% to 50% of worldwide net product sales, projected to leave both companies with approximately the same profit as under the original structure. BioMarin has continued to manufacture the drug throughout, with Genzyme responsible for global marketing and sales.

Current status

Aldurazyme remains FDA-approved and currently marketed, manufactured by BioMarin and commercialized by Sanofi's Genzyme division under the restructured 2008 agreement. As of early 2026 it remains the only FDA-approved disease-specific drug for MPS I of any phenotype — a genuinely long run without a direct enzyme-replacement rival, unlike the Gaucher, Fabry and Pompe disease clusters covered elsewhere on this site, each of which now has multiple competing approved options. Hematopoietic stem cell transplantation remains the preferred approach for young children with severe Hurler syndrome, often with laronidase used as a bridge before and after transplant, while enzyme replacement alone remains the standard of care for the more attenuated Hurler-Scheie and Scheie forms. Several gene-therapy and engineered-cell candidates aimed at MPS I are in clinical development, though none is FDA-approved — and REGENXBIO's RGX-111 gene-therapy program, one of the more advanced, was placed on an FDA clinical hold in January 2026 after a treated participant developed a brain tumor, a reminder that laronidase's decades of real-world safety data still set the bar any newer approach for this disease has to clear.