Home » Drug Information » FDA Approved Drugs » 2003
Medical Areas: Endocrinology | Musculoskeletal | Pediatrics/Neonatology | Pulmonary/Respiratory Diseases
View By:YearCompanyConditionsTherapeutic AreasDrug Names
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approval Status: Approved May 2003
Treatment Area: Mucopolysaccharidosis I
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
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.
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
Adverse events associated with the use of Fabrazyme may include
(but are not limited to) the following:
- Upper respiratory tract infection
- Injection site reaction
- Vein disorder
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
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
Clarke, L.A. (1997) Clinical diagnosis of
lysosomal storage diseases. In: Organelle Diseases. Clinical
Features, Diagnosis, Pathogenesis and Management. Applegarth,
D.A., Dimmick, J.E., and Hall, J.G. (eds.). Chapman and Hall
Medical, London, pp. 37.
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,
Wraith, J.E. (1995) The mucopolysaccharidoses:
A clinical review and guide to management. Arch Dis Child