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5 mL vials containing 5 mg powder for reconstitution
20 mL vials containing 35 mg powder for reconstitution
Approved indication: Fabry's disease
Australian Medicines Handbook section 10.6
Lysosomal storage diseases are caused by inborn errors of metabolism. The lack of a specific enzyme results in the substrate accumulating inside lysosomes. Fabry's disease results from an X-linked recessive genetic defect which causes a deficiency of Î±-galactosidase A. This deficiency leads to the accumulation of globotriaosylceramide in the lysosomes in blood vessel walls. Patients usually die of cerebrovascular disease, myocardial infarction, heart failure or renal failure.
Agalsidase beta is a recombinant form of Î±-galactosidase A produced by genetically engineered Chinese hamster ovary cells. To replace the deficient enzyme requires an intravenous infusion, for at least two hours, every two weeks.
The infused agalsidase is taken up by endothelial lysosomes and has an elimination half-life of 45-100 minutes. As agalsidase is broken down by peptide hydrolysis, impaired liver or renal function may have little effect on clearance.
As the incidence of Fabry's disease is less than 1 in 100 000 births, clinical trials involve only a few patients. In a placebo-controlled trial 29 adult patients were treated with agalsidase beta for 20 weeks. After 11 infusions, 69% of this group had no microvascular endothelial deposits of globotriaosylceramide in more than 50% of the capillaries seen on renal biopsy. Deposits were also significantly reduced in the skin and the heart. There was also a significant reduction in the amount of globotriaosylceramide in the urine.1
Agalsidase is a protein so infusion reactions are common. Approximately half the patients will have an adverse reaction on the day of the infusion. They may develop headache, fever, muscle pain and altered sensation. Oedema, hypertension, nausea and vomiting are also very common.
More than 80% of patients will develop IgG antibodies to agalsidase. The long-term consequences of the seroconversion are unknown, but no evidence of immune-complex glomerulonephritis was seen in the clinical trials. Although agalsidase improves the pathological appearance of tissue samples, its clinical benefits are unknown. Agalsidase did not reduce the pain experienced by patients with Fabry's disease significantly more than placebo.1 Longer-term follow-up shows some improvement in pain and quality of life, but there were no statistically significant changes. The effect of agalsidase in children is unknown.
Agalsidase is likely to be expensive, but other companies are genetically engineering Î±-galactosidase A so competition may help to control costs. In the absence of clinical outcomes calculating cost-effectiveness could be a problem.
- International Collaborative Fabry Disease Study Group. Safety and efficacy of recombinant human Î±-galactosidase A replacement therapy in Fabry's disease. N Engl J Med 2001;345:9-16.