Abstract
Purpose:To evaluate the safety of velaglucerase alfa in patients with type 1 Gaucher disease who received velaglucerase alfa in the US treatment protocol HGT-GCB-058 (ClinicalTrials.gov identifier NCT00954460) during a global supply shortage of imiglucerase.Methods:This multicenter open-label treatment protocol enrolled patients who were either treatment naïve or had been receiving imiglucerase. Patients received intravenous velaglucerase alfa every other week at a dose of 60 U/kg (treatment naïve) or 15–60 U/kg (previously treated).Results:A total of 211 (including six treatment-naïve) patients were enrolled. Among the 205 previously treated patients, 35 (17.1%) experienced an adverse event considered related to study drug. Among the six treatment-naïve patients, one had an adverse event considered related to study drug. Infusion-related adverse events occurred in 28 (13.3%) of the 211 patients and usually occurred during the first three infusions. De novo, nonneutralizing, anti–velaglucerase alfa antibodies developed during treatment in one (<1.0%) previously treated patient and none of the treatment-naïve patients.Conclusion:The currently observed safety profile was consistent with those previously reported for imiglucerase and velaglucerase alfa phase III clinical trials. These results support the safety of initiating treatment with velaglucerase alfa or transitioning patients from imiglucerase therapy to velaglucerase alfa therapy.
Highlights
Gaucher disease type 1 (GD1) is an autosomal recessively inherited lysosomal storage disease.[1]
Velaglucerase alfa enzyme therapy is approved for the long-term treatment of adults and children with GD1 in >40 countries, including the United States, European Union member states, and Israel.[7]
A total of 189 (89.6%) patients completed the protocol, and 22 patients discontinued; all of these had been previously treated and the primary reasons for discontinuation were the following: withdrawal of consent: 17 (8.1%); adverse events (AEs): 3 (1.4%; of these, 2 patients experienced mildly increased blood pressure considered possibly related to study drug and 1 patient had moderate infusion-related nausea; all resolved without any sequelae); termination from the protocol by the investigator: 1 (0.5%; patient was not compliant with infusion visits); and others: 1 (0.5%; patient moved out of the country and was no longer eligible to participate)
Summary
Gaucher disease type 1 (GD1) is an autosomal recessively inherited lysosomal storage disease.[1] Its pleotropic manifestations result from mutations in the gene encoding glucocerebrosidase (GBA1)[2] and consequent dysfunction of the cognate enzyme. The resultant accumulation of glucosylceramide in the reticuloendothelial system leads to the major clinical features.[1] Lipid-laden macrophages, called Gaucher cells, accumulate in various organs, including the liver, spleen, and bone marrow, resulting in cytopenias, hepatomegaly, splenomegaly, osteonecrosis, osteoporosis, and other bone lesions that occur by unclear molecular mechanisms.[1]. Most patients with GD1 who are on treatment receive exogenous enzyme. Available enzyme therapies include imiglucerase (approved by the US Food and Drug Administration (FDA) in 1994 and by the European Medicines Agency in 1997), velaglucerase alfa (approved by the FDA and European Medicines Agency in 2010), and taliglucerase alfa (approved for adults by the FDA in 2012), all of which are generally administered intravenously every other week (EOW) at infusion centers, physician offices, or in a supervised home setting.[3,4,5,6] Velaglucerase alfa enzyme therapy is approved for the long-term treatment of adults and children with GD1 in >40 countries, including the United States, European Union member states, and Israel.[7]
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