Positive results from the first of three Phase III studies of Velaglucerase alfa, an enzyme replacement therapy in development for the treatment of Type 1 Gaucher disease, have been reported.

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 multicenter, randomized, double-blind, two dose study of Velaglucerase alfa in patients with Type 1 Gaucher disease. The primary goal of this study was to evaluate the safety and efficacy of Velaglucerase alfa in 25 patients with Type 1 Gaucher disease.

Patients aged two years and older who were treatment naïve were eligible to participate in the study if they presented with disease-related anemia and had at least one of the following clinical manifestations of Gaucher disease: thrombocytopenia, moderate splenomegaly or a readily palpable enlarged liver.

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 hemoglobin 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 hemoglobin, platelet count, and spleen volume were also demonstrated. The magnitude of changes in the 45 U/kg dose was also clinically important, and a trend in liver volume reduction was observed.

Velaglucerase alfa was found to be generally well tolerated with no drug-related serious adverse events reported in the trial. No patients withdrew from the trial due to an adverse event.
Most of the drug-related adverse events were reported in association with Velaglucerase alfa infusions, all of which were mild and resolved without sequelae.

Gaucher disease is an autosomal recessive disease and the most prevalent lysosomal storage disorder ( LSD ), with an incidence of about 1 in 20,000 live births. Despite the fact that Gaucher Disease consists of a phenotype, with varying degrees of severity, it has been sub-divided in three subtypes according to the presence or absence of neurological involvement. It is also the most common genetic disease affecting Ashkenazi Jewish people ( Eastern, Central and Northern European ancestry ), with a carrier frequency of 1 in 10 ( John Barranger and Ed Ginns 1989 ). 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 diagnosed population of Gaucher disease patients is approximately 7,000. Based on incidence, the estimated total world population is likely to be between 10,000 and 15,000 patients.

Source: Shire, 2009

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