Velaglucerase (VPRIV) for the Treatment of Gaucher disease (Enzyme Replacement Therapy)

VPRIV™ (velaglucerase alfa for injection)

Gaucher disease is an autosomal recessive disorder caused by mutations in the GBA gene, which results in a deficiency of the lysosomal enzyme beta-glucocerebrosidase. Glucocerebrosidase catalyzes the conversion of the sphingolipid glucocerebroside into glucose and ceramide. The enzymatic deficiency causes an accumulation of glucocerebroside primarily in the lysosomal compartment of macrophages, giving rise to foam cells or "Gaucher cells". In this lysosomal storage disorder (LSD), clinical features are reflective of the accumulation of Gaucher cells in the liver, spleen, bone marrow, and other organs. The accumulation of Gaucher cells in the liver and spleen leads to organomegaly. The presence of Gaucher cells in the bone marrow and spleen leads to clinically significant anemia and thrombocytopenia.

Velaglucerase alfa is a glycoprotein of 497 amino acids; with a molecular weight of approximately 63 kDa. Velaglucerase alfa has the same amino acid sequence as the naturally occurring human enzyme, glucocerebrosidase. Velaglucerase alfa contains 5 potential N-linked glycosylation sites; four of these sites are occupied by glycan chains. Velaglucerase alfa is manufactured to contain predominantly high mannose-type Nlinked glycan chains. The high mannose type N-linked glycan chains are specifically recognized and internalized via the mannose receptor present on the surface on macrophages, the cells that accumulate glucocerebroside in Gaucher disease. Velaglucerase alfa catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide in the lysosome.

Initial U.S. Approval: 2010

VPRIV (velaglucerase alfa for injection) is a hydrolytic lysosomal glucocerebroside-specific enzyme indicated for long-term enzyme replacement therapy (ERT) for pediatric and adult patients with type 1 Gaucher disease. 

60 Units/kg administered every other week as a 60-minute intravenous infusion.
Patients currently being treated with imiglucerase for Gaucher disease can be switched to VPRIV. Patients previously treated on a stable dose of imiglucerase are recommended to begin treatment with VPRIV at that same dose when they switch from imiglucerase to VPRIV.
Physicians can make dosage adjustments based on the achievement and maintenance of each patient’s therapeutic goals. 
Clinical trials have evaluated doses ranging from 15 Units/kg to 60 Units/kg every other week 

 Lyophilized powder to be reconstituted and diluted for infusion. 
Available in 200 Units and 400 Units single-use vials.


Hypersensitivity reactions: Treatment with VPRIV should be carefully re-evaluated in the presence of significant evidence of hypersensitivity to the product. 
Infusion-related reactions 

The most common adverse reactions during clinical studies were infusion-related reactions (5.2, 6.1). 
Other commonly observed adverse reactions in ≥ 10% of patients were: headache, dizziness, abdominal pain, nausea, back pain, joint pain, upper respiratory tract infection, activated PTT prolonged, fatigue/asthenia, and pyrexia.