Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Approved indication: Gaucher's disease type 1
glass vials containing 400 units as lyophilised powder for reconstitution
Australian Medicines Handbook section: Appendix A
Gaucher's disease is one of the lysosomal storage diseases. A genetic disorder results in a lack of glucocerebrosidase. This enzyme deficiency leads to accumulation of glucocerebroside in macrophages, with enlargement of the liver and spleen. There can be bone involvement, anaemia and thrombocytopenia.
Enzyme replacement therapy has been available since the 1990s, first with alglucerase and later with the genetically engineered imiglucerase (see Aust Prescr 1999;22:95-8). While imiglucerase was produced from Chinese hamster ovary cells, velaglucerase alfa is produced from human fibroblast cell lines. It has the same amino acid sequence as natural glucocerebrosidase.
As Gaucher's disease is relatively rare (only about 400 patients in Australia), the clinical trials of velaglucerase have been small. In a trial of adults with no recent use of imiglucerase, 12 symptomatic patients were given intravenous infusions of velaglucerase every other week for up to nine months. There were improvements in their haemoglobin and platelet counts. Liver and spleen volumes reduced. These improvements were sustained in nine patients who entered an extension study for an additional 39 months.1
Two doses of velaglucerase were compared in a 12-month study in children and adults. In the 12 patients who were treated at a dose of 60 units/kg the mean haemoglobin increased from 108.3 g/L to 125.5 g/L. It increased from 107.2 g/L to 131.6 g/L in the 13 patients given 45 units/kg. Platelet counts increased by 50.88 x 109/L with 60 units/kg and by 40.92 x 109/L with 45 units/kg. While both doses decreased spleen volume, there was no significant decrease in liver volume.
The 60 units/kg dose has been recommended. This is given as a one hour infusion every other week. A dose reduction may be possible depending on the response.1
A phase III study randomised 34 patients to be treated with velaglucerase 60 units/kg or imiglucerase for nine months. The patients' haemoglobin concentration was the primary outcome. Their mean haemoglobin increased by 16.2 g/L with velaglucerase and by 14.9 g/L with imiglucerase. There was also an increase in mean platelet counts and decreases in liver and spleen volumes. These results showed that the efficacy of velaglucerase is not inferior to that of imiglucerase.
Another trial studied 40 patients who had already been treated with imiglucerase for at least 30 months. When they were switched to velaglucerase there were no significant changes in haemoglobin or platelet counts over the next 12 months.
A shortage of imiglucerase in 2009 led to patients' treatments being reduced. Some of the effects of reduced treatment were reversed in a group of 32 patients who were switched to velaglucerase. However, imaging in ten of these patients detected an increase in liver volume in five patients after six months of velaglucerase.2
The safety data for velaglucerase came from 94 adults and children. Reactions to the infusion were the most common problem. These included headache, fever, nausea, dizziness and altered blood pressure. Adverse events which were more frequent than with imiglucerase included headache, fever, diarrhoea, hypertension and arthralgia. Patients may also complain of bone pain or back pain. No data are available concerning the use of velaglucerase in pregnancy or lactation.
Some patients develop antibodies to imiglucerase. Although hypersensitivity reactions have occurred with velaglucerase, so far only one patient has developed antibodies to velaglucerase. Caution is needed if the patient is hypersensitive to other enzyme replacement products.
Enzyme replacement therapy is expensive. Although the number of patients needing therapy is small, there is now another option for treatment.
The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
Notes on references
At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).
At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.europa.eu).
At the time the comment was prepared, information about this drug was available on the website of the Therapeutic Goods Administration (www.tga.gov.au/industry/pm-auspar.htm).
- Zimran A, Altarescu G, Philips M, Attias D, Jmoudiak M, Deeb M, et al. Phase 1/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience. Blood 2010;115:4651-6.
- van Dussen L, Cox TM, Hendriks EJ, Morris E, Akkerman EM, Maas M, et al. Effects of switching from a reduced dose imiglucerase to velaglucerase in type 1 Gaucher disease: clinical and biochemical outcomes. Haematologica 2012 Jul 6 (Epub ahead of print). doi:10.3324/haematol.2011.059071.