Shire’s velaglucerase alfa program is the largest and most comprehensive set of Phase III clinical trials conducted to date for Gaucher disease. More than 100 patients at 24 sites in ten countries around the world have participated in the clinical studies. Velaglucerase alfa is made using Shire’s proprietary technology in a human cell line. The enzyme produced has the exact human amino acid sequence and carries a human glycosylation pattern.

The first trial in the Phase III program to be completed was a multicentre, randomized, double-blind, two-dose study, the primary goal of which was to evaluate the safety and efficacy of velaglucerase alfa in 25 patients with Type 1 Gaucher disease. Patients were randomized to receive velaglucerase alfa at either 45 U/kg or 60 U/kg for a duration of 12 months.

In the trial, the primary endpoint was reached, with patients benefiting from a clinically important and statistically significant (p<0.0001) increase in mean haemoglobin concentration compared with baseline after receiving velaglucerase alfa at 60 U/kg IV every other week for 12 months. Statistically significant improvements compared with baselines were also observed in platelet and spleen sizes, and nominally significant improvements were observed in liver size at this dose.

Results were clinically important as defined by standard criteria and consistent with the previously published Phase I/II data. At the 45 U/kg IV dose, statistically significant improvements in haemoglobin, platelet count and spleen volume were also demonstrated. The magnitude of changes in the 45U/kg dose was also clinically important, and a trend in liver volume reduction was observed. The 60U/kg dose performed numerically as well as or better than the 45U/kg dose across all measured clinical endpoints. Velaglucerase alfa was found to be generally well tolerated, and no drug-related serious adverse events were reported in the trial. The specific data from this trial will be presented at a scientific meeting later this year.

Gaucher disease is an autosomal recessive disease and the most prevalent lysosomal storage disorder, with an incidence of approximately 1 in 20,000 live births. Despite the fact that Gaucher disease consists of a phenotype, with varying degrees of severity, it has been subdivided in three subtypes according to the presence or absence of neurological involvement. This panethnic disease involves many organ systems, such as liver, spleen, lungs, brain, metabolism and bone marrow.

Gaucher disease results from a specific enzyme deficiency in the body, caused by a genetic mutation received from both parents. The disease course is quite variable, ranging from no outward symptoms to severe disability and death. Carrier status can be detected through blood or saliva to identify potential carriers of the Gaucher gene. Gaucher disease can be diagnosed early through a blood test. Worldwide, the estimated total world population of Gaucher disease patients is likely to be between 10,000 and 15,000 patients.