Naglazyme (Cedarglen Investments)
glass vials containing 5 mg/5 mL
Approved indication: mucopolysaccharidosis VI
Australian Medicines Handbook Appendix A
Mucopolysaccharidosis VI is one of the lysosomal storage diseases. It is also known as Maroteaux-Lamy syndrome. As there is an inherited deficiency of the enzyme acetylgalactosamine sulfatase, the degradation of dermatan sulfate is reduced. This substrate accumulates in the lysosomes resulting in deformities, organ damage and growth retardation. Hydrocephalus can develop, but mental development is usually normal. The condition may progress slowly or rapidly. Bone marrow transplant helps a few patients, but has a high mortality and morbidity.
Galsulfase is a recombinant form of acetylgalactosamine sulfatase, produced using Chinese hamster ovarian cells. The solution has to be infused intravenously over at least four hours. Although the half-life of galsulfase is less than 30 minutes, it only needs to be infused once a week.
As mucopolysaccharidosis VI is a very rare disease the main trial of galsulfase only included 39 patients. They were given a weekly infusion of the enzyme or a placebo for 24 weeks. Although the patients were randomised, there was a significant baseline difference between the groups. Before treatment the mean distance patients in the galsulfase group could walk in 12 minutes was 227 metres, whereas the placebo group could cover 381 metres. At the end of the trial the patients given galsulfase could walk 336 metres, while those in the placebo group could walk 399 metres. The mean change in the enzyme group (109 metres) was significantly greater than in the placebo group (26 metres). The mean number of stairs patients could climb in three minutes increased from 19 to 27 with galsulfase and from 31 to 33 with placebo.1
Common adverse events during treatment with galsulfase are fever, headache, arthralgia, abdominal pain, ear pain, diarrhoea and vomiting. There can be severe adverse reactions to the infusion, with urticaria, bronchospasm, respiratory distress and apnoea. Although patients should be given antihistamines before each treatment, this will not prevent all the infusion reactions. These reactions can occur for the first time after many weeks of infusions, so resuscitation equipment must always be available during treatment. Nearly all patients develop antibodies to galsulfase, but these do not predict the severity of the infusion reactions.
The assessment of galsulfase was complicated by the imbalance between the groups in the clinical trial.1Re-analysis of the data by regulatory authorities was needed to confirm the efficacy of the enzyme. There is also evidence, from a 24-week extension of the trial, that patients who switch to galsulfase from placebo will increase the distance they can walk in 12 minutes (mean increase 66 metres). This extension was 'open label' so there is some uncertainty about the benefit. Galsulfase had no significant effect on joint pain and stiffness, but the trial was not powered to show a difference.1In view of these uncertainties and the unknown long-term effect of anti-galsulfase antibodies on clinical outcomes, patients given galsulfase should be in a clinical surveillance program.
The Transparency Score is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
- Harmatz P, Giugliani R, Schwartz I, Guffon N, Teles EL, Sa Miranda MC, et al; the MPS VI Phase 3 Study Group. Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study. J Pediatr 2006;148:533-9.
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