General Information

Aldurazyme (laronidase) is a recombinant alpha-L-iduronidase enzyme replacement therapy for the treatment of mucopolysaccharidosis I (MPS-I).

Aldurazyme is indicated for patients aged 5 to 65 with Hurler and Hurler-Scheie forms of Mucopolysaccharidosis I (MPS I) and for patients with the Scheie form who have moderate to severe symptoms.

Aldurazyme is supplied as a sterile solution in clear Type I glass 5 mL vials (2.9 mg laronidase per 5 mL). The recommended dosage regimen of Aldurazyme is 0.58 mg/kg of body weight administered once weekly as an intravenous infusion.

Clinical Results

FDA approval of Aldurazyme was based on a randomized, placebo-controlled clinical trial of 45 MPS I subjects. One subject was clinically assessed as having the Hurler form, 37 the Hurler-Scheie form and 7 the Scheie form. All subjects had a baseline forced vital capacity (FVC) less than or equal to 77% of predicted. Subjects received Aldurazyme (0.58 mg/kg) or placebo once weekly for 26 weeks and were treated with antipyretics and antihistamines before each infusion. The primary efficacy outcome assessments were FVC and distance walked in 6 minutes (6-minute walk test, 6MWT).

Results showed that after 26 weeks, subjects treated with Aldurazyme showed improvement in FVC and in 6MWT compared to placebo-treated subjects. Data demonstrated that liver size and urinary glycosaminoglycan (GAG) levels decreased in subjects treated with Aldurazyme compared with subjects treated with placebo. No subject in the group receiving Aldurazyme reached the normal range for urinary GAG levels during this 6-month study.

All 45 patients received open-label Aldurazyme for 36 weeks following the double-blind period. Maintenance of mean FVC and an additional increase in mean 6MWT distance were observed compared to the start of the open-label period among subjects who were initially randomized to and then continued to receive Aldurazyme. Among subjects who had been initially randomized to placebo, improvements from baseline in mean FVC and 6MWT distance were observed compared to the start of the open-label.

Approximately 91% of subjects treated with Aldurazyme were positive for antibodies to laronidase. The clinical significance of antibodies to Aldurazyme is not known, including the potential for product neutralization.

Mechanism of Action

Aldurazyme (laronidase), an enzyme replacement therapy is a polymorphic variant of the human enzyme, ?-L-iduronidase that is produced by recombinant DNA technology in a Chinese hamster ovary cell line. By replacing the missing enzyme, Aldurazyme helps the body break down the glycosaminoglycans (GAG) that builds up in cells and tissues. Regular replacement of the enzyme alpha-L-iduronidase with Aldurazyme helps prevent the buildup of GAG.

Aldurazyme was shown to significantly reduce the levels of GAG excreted in the urine, and decrease the size of livers enlarged by the disorder. This showed that the drug works effectively at a biochemical level.

Literature References

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Fratantoni, J.C., Neufeld, E.F., Uhlendorf, B.W., and Jacobson, C.B. (1969b) Intrauterine diagnosis of the Hurler and Hunter syndromes. N Engl J Med 280: 686.

Neufeld, E.F., and Muenzer, J. (2001) The mucopolysaccharidoses. In: The Metabolic and Molecular Bases of Inherited Disease. Scriver, C.R., Beaudet, A.L., Sly, W.S., Valle, D., Childs, B., Kinzler, K.W., and Vogelstein, B. (eds.). 8th edition, Vol. III. McGraw-Hill, Medical Publishing Division, pp. 3421.

Wraith, J.E. (1995) The mucopolysaccharidoses: A clinical review and guide to management. Arch Dis Child 72: 263.