New molecular entity: Velaglucerase alpha for injection (VPRIV) was approved February 2010 as an enzyme replacement therapy for the long-term treatment of type 1 Gaucher disease in pediatric and adult patients.
After priority review, velaglucerase alpha for injection has received FDA approval as an enzyme replacement therapy for the long-term treatment of type 1 Gaucher disease in pediatric and adult patients. Gaucher disease is the most common lysosomal storage disorder (about 1 in 50,000 to 1 in 100,000 people in the general population have the disease), which is caused by an autosomal recessive mutation in the glucocerebrosidase gene resulting in a deficiency in beta-glucocerebrosidase. Glucocerebrosidase deficiency leads to an accumulation of glucocerebroside, the collection of foam or "Gaucher" cells in the liver, spleen, and bone marrow, finally resulting in hepato- and splenomegaly, anemia, and thrombocytopenia. Velaglucerase alpha is a human cell line derived hydrolytic lysosomal glucocerebroside-specific enzyme that can be used to correct this deficiency. Velaglucerase alpha is an alternative to imiglucerase, another enzyme replacement therapy currently in short supply because of viral contamination at a manufacturing facility.
Efficacy. The safety and effectiveness of velaglucerase alpha for injection was assessed in 3 clinical studies involving 99 patients with type 1 Gaucher disease aged 4 years and older. Studies I and II were 12- and 9-month evaluations, respectively, conducted in patients who were not currently receiving Gaucher disease-specific therapy. These studies demonstrated velaglucerase alpha could positively effect hemoglobin concentrations, platelet counts, and spleen volume compared with baseline and imiglucerase. Study III was a 12-month, open-label, single-arm evaluation conducted in patients who were receiving imiglucerase treatment immediately before starting velaglucerase alpha. After switching from imiglucerase, patients maintained stable hemoglobin and platelet concentrations while receiving velaglucerase alpha.
Safety. The most common adverse effects observed in patients receiving velaglucerase alpha, but previously naïve to enzyme replacement therapy, were infusion-related reactions (51.9%). These infusion-related reactions were generally mild and, in treatment-naïve patients, their onset occurred mostly during the first 6 months of treatment and tended to occur less frequently with time. Other common adverse reactions observed during clinical trials included headache (35.2%); dizziness (22.2%); pyrexia (22.2%); abdominal (18.5%), back (16.7%) or joint (14.8%) pain; fatigue/asthenia (13.0%); prolonged activated partial thromboplastin time (11.1%); and nausea (5.6%). Adverse reactions more commonly seen in pediatric patients compared with those observed in adult patients (>10% difference) included rash, upper respiratory tract infection, prolonged activated partial thromboplastin time, and pyrexia.