5 mL vials containing 100 U/mL
Approved indication: mucopolysaccharidosis I
Mucopolysaccharidosis I is a lysosomal storage disease caused by an inborn error of metabolism. Severe cases are also known as Hurler disease. The patient has a deficiency of the enzyme Î±–L–iduronidase which leads to an accumulation of substrates inside the lysosomes. This gradually impairs cell function and results in developmental delay, hepatosplenomegaly, joint stiffness, neurological problems, airway obstruction and abnormal facial features. Children with Hurler disease usually die before the age of 10 years, less severe cases may live into their 20s.
Laronidase is a recombinant form of the deficient enzyme. It is genetically engineered, using Chinese hamster ovary cells, to have exactly the same amino acid sequence as the human enzyme.
The aim of treatment is to metabolise the stored substrate and prevent further accumulation. To achieve this laronidase is diluted and given as an infusion over four hours. Although the half-life of laronidase is 2–4 hours, only a weekly dose is required. The molecule is metabolised by peptide hydrolysis.
In a 52-week study of 10 patients there was a 25% decrease in the size of the liver and a 20% decrease in the size of the spleen. There was a 63% reduction in the amount of substrate appearing in the urine. The range of joint movement increased and the prepubertal patients showed improved growth. Lung function also improved.1
A larger double-blind trial randomised 22 patients to receive laronidase and 23 to receive a placebo for 26 weeks. Active treatment resulted in a significant reduction in liver size and the excretion of substrates.
Infusing patients with peptides can cause hypersensitivity reactions. As 32% of patients may have a reaction to the infusion, it is important that they are given antipyretics and antihistamines before their infusions. Many patients will produce antibodies to laronidase, but they can also develop an immune tolerance.2 It is therefore unknown if these antibodies will alter the long-term effectiveness of treatment.
Although the efficacy studies show some improvements for patients, not all of the benefits are statistically significant. In the larger trial the forced vital capacity significantly improved, but there was no significant change in the apnoea/hypopnea index. Although, after 26 weeks of treatment, the patients could walk nearly 20 metres further in six minutes, the advantage over placebo was not statistically significant. The effect of laronidase on the nervous system is uncertain and it is only indicated for non-neurological manifestations of the disease.
Although bone marrow transplantation can be helpful it will not be an option for many patients. Treatment with laronidase will be an expensive alternative and the long-term outcomes will remain unknown for many years.
The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
- Kakkis ED, Muenzer J, Tiller GE, Waber L, Belmont J, Passage M. Enzyme replacement therapy in mucopolysaccharidosis I. N Engl J Med 2001;344:182-8.
- Kakavanos R, Turner CT, Hopwood JJ, Kakkis ED, Brooks DA. Immune tolerance after long-term enzyme replacement therapy among patients who have mucopolysaccharidosis I. Lancet 2003;361:1608-13.
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