Shire also announced positive results from the final two Phase III studies of velaglucerase alfa: both studies reached all of their primary and secondary endpoints. ’The submission of the NDA for velaglucerase alfa, earlier than previously announced, is an important milestone for Shire, bringing us another step closer to providing a new treatment option for patients with Type 1 Gaucher disease,’ said Sylvie Gregoire, President of Shire Human Genetic Therapies.

All three Phase III studies of velaglucerase alfa demonstrated positive results. More than 100 patients at 24 sites in ten countries around the world have participated in the clinical studies, and the product was generally well tolerated in both treatment-naive and previously treated Gaucher patients. The three studies included Study 032, which studied velaglucerase alfa in naive patients; Study 039, which was a head-to-head study of velaglucerase alfa and imiglucerase; and Study 034, which was a switch study from imiglucerase to velaglucerase alfa.

As reported on 03 August 2009, Study 032 in naive patients met its primary endpoint, which evaluated change in haemoglobin concentrations from baseline.

Study 039 was a nine-month, randomized, double-blind efficacy study in 34 treatment-naive patients aged two years and older that compared velaglucerase alfa to imiglucerase. Patients 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 either velaglucerase alfa or imiglucerase at 60 U/kg every other week. The primary endpoint was the comparison of increases in haemoglobin concentrations between the velaglucerase alfa and imiglucerase groups. Secondary endpoints were comparisons of increases in platelet counts, decreases in organ volumes, and surrogate markers of Gaucher disease. Velaglucerase alfa demonstrated robust clinical efficacy that was comparable to imiglucerase in all endpoints.

Study 034 was a 12-month switch study in 40 clinically stable Type 1 Gaucher patients aged two years and older who had been receiving treatment with imiglucerase at doses ranging between 15 U/kg and 60 U/kg every other week for a minimum of 30 consecutive months. This study assessed the safety of patients switched from imiglucerase to velaglucerase alfa administered at the same number of units as their imiglucerase dose. In this study, haemoglobin concentrations, platelet counts and organ volumes were sustained through 12 months of velaglucerase alfa treatment, and the therapy was generally well tolerated.

The specific data from all three trials will be presented at future scientific meetings.

Gaucher disease is an autosomal recessive disorder caused by mutations in the GBA gene that results in a deficiency of the lysosomal enzyme beta-glucocerebrosidase. This enzymatic deficiency causes an accumulation of glucocerebroside, primarily in macrophages. In this lysosomal storage disorder, clinical features are reflective of the distribution of Gaucher cells in the liver, spleen, bone marrow, skeleton and lungs. The accumulation of glucocerebrosidase in the liver and spleen leads to organomegaly. Bone involvement results in skeletal abnormalities and deformities, as well as bone pain crises. Deposits in the bone marrow and splenic sequestration lead to clinically significant anaemia and thrombocytopenia. Velaglucerase alfa supplements or replaces beta-glucocerebrosidase, the enzyme that catalyzes the hydrolysis of glucocerebroside, reducing the amount of accumulated glucocerebroside and correcting the pathophysiology of Gaucher disease.