Laronidase (Aldurazyme) for the Treatment of mucopolysaccharidosis I (MPS I) Hurler Syndrome

ALDURAZYME (laronidase) Solution for intravenous infusion only

Mucopolysaccharide storage disorders are caused by the deficiency of specific lysosoma l enzymes required for the catabolism of glycosaminoglycans (GAG). Mucopolysaccharidosis I (MPS I) is characterized by the deficiency of a-L-iduronidase, a lysosomal hydrolase which catalyses the hydrolysis of terminal a-L-iduronic acid residues of dermatan sulfate and heparan sulfate. Reduced or absent a-L-iduronidase activity results in the accumulation of the GAG substrates, dermatan sulfate and heparan sulfate, throughout the body and leads to widespread cellular, tissue, and organ dysfunction. 

ALDURAZYME (laronidase) is a polymorphic variant of the human enzyme, a-L-iduronidase that is produced by recombinant DNA technology in a Chinese hamster ovary cell line. a-L-iduronidase (glycosaminoglycan a-L-iduronohydrolase, EC is a lysosomal hydrolase that catalyses the hydrolysis of terminal a-L-iduronic acid residues of dermatan sulfate and heparan sulfate. Laronidase is a glycoprotein with a molecular weight of approximately 83 kD. The predicted amino acid sequence of the recombinant form, as well as the nucleotide sequence that encodes it, are identical to a polymorphic form of human a-L-iduronidase. The recombinant protein is comprised of 628 amino acids after cleavage of the N-terminus and contains 6 N-linked oligosaccharide modification sites. Two oligosaccharide chains terminate in mannose-6-phosphate sugars

The rationale of ALDURAZYME therapy in MPS I is to provide exogenous enzyme for uptake into lysosomes and increase the catabolism of GAG. ALDURAZYME uptake by cells into lysosomes is most likely mediated by the mannose-6-phosphate-terminated oligosaccharide chains of laronidase binding to specific mannose-6-phosphate receptors.

Initial U.S. Approval: 2003

Dosage and Administration (8/2009) 

 ALDURAZYME is indicated for patients with Hurler and Hurler-Scheie forms of mucopolysaccharidosis I (MPS I) and for patients with the Scheie form who have moderate to severe symptoms. The risks and benefits of treating mildly affected patients with Scheie form have not been established. ALDURAZYME has been shown to improve pulmonary function and walking capacity. ALDURAZYME has not been evaluated for effects on the central nervous system manifestations of the disorder.

0.58 mg/kg of body weight administered once weekly as an intravenous (IV) infusion. 

Solution for IV infusion: 2.9 mg/5 mL vial (3


 Life-threatening anaphylactic reactions have been observed in some patients during or up to 3 hours after infusion. Patients with an acute illness at the time of infusion may be at greater risk for infusion-related reactions. Appropriate medical support should be available when ALDURAZYME is administered. If anaphylactic or other severe allergic reactions occur, immediately discontinue the infusion and initiate appropriate treatment, which may include ventilatory support, treatment with inhaled betaadrenergic agonists, epinephrine, and IV corticosteroids.
Pretreatment with antipyretics and/or antihistamines is recommended prior to the infusion to reduce the risk of infusion-related allergic reactions. If infusion-related reactions occur, decreasing the infusion rate, temporarily stopping the infusion, and/or administering additional antipyretics and/or antihistamines may ameliorate the symptoms.

The most frequently occurring adverse reactions occurring in at least 10% of patients 6 years and older are rash, upper respiratory tract infection, injection site reaction, hyperreflexia, paresthesia, and vein disorder. The most commonly reported adverse reactions occurring in at least 10% of patients less than 6 years of age were pyrexia, chills, increased blood pressure, tachycardia, and decreased oxygen saturation.