New Gaucher Treatment Approved

Kate Traynor

BETHESDA, MD 01 March 2010—FDA and Shire plc on Friday announced the approval of velaglucerase alfa for injection, or Vpriv, an enzyme-replacement therapy for the long-term treatment of type 1 Gaucher disease.

Velaglucerase alfa is identical in amino acid sequence to glucocerebrosidase but is produced in a human fibroblast cell line, according to the drug's FDA-approved labeling (PDF).

In patients with Gaucher disease, glucocerebrosidase deficiency leads to the buildup of lipids in storage cells in the liver, spleen, lymph nodes, alveolar capillaries, and bone marrow. The buildup can result in enlargement of the liver or spleen, anemia, or thrombocytopenia. Type 1 Gaucher disease affects about 1 or 2 people per 100,000 in the general population but is more common among people of Ashkenazi Jewish ancestry.

Velaglucerase alfa was made available last year to patients with Gaucher disease through an expanded-access program. According to Shire, the so-called treatment protocol was developed at the request of FDA in response to a shortage of the only FDA-licensed enzyme-replacement therapy for the disease, imiglucerase.

The recommended starting dosage of velaglucerase alfa is 60 units/kg administered every other week as a 60-minute i.v. infusion. The infusion apparatus should include an inline low-protein-binding 0.2 micrometer filter. Because of a lack of compatability data, no other products should be infused in the tubing along with velaglucerase alfa.

Dosage adjustments may be made on the basis of "achievement and maintenance of each patient’s therapeutic goals," the labeling states.

Patients who are switching therapy to velaglucerase alfa from a stable dosage of imiglucerase should receive that same dosage of velaglucerase alfa as a starting point, according to the labeling.

Velaglucerase alfa is packaged in single-use vials of 200 or 400 Units each. The lyophilized powder should be reconstituted with Sterile Water for Injection, USP, and diluted with 0.9% sodium chloride injection to a final concentration of 100 units/mL.

The reconstituted product should be used immediately, if possible, according to the labeling. Otherwise, diluted velaglucerase alfa can be stored at 2–8 degrees C and the infusion completed within 24 hours after reconstitution.

Infusion-related reactions characterized by headache, dizziness, hypotension, hypertension, nausea, fatigue, or fever were the most frequent adverse events reported in clinical trials of velaglucerase alfa, according to the drug's labeling.

Other adverse events that affected at least 10% of patients treated with the enzyme product included abdominal, back or joint pain, upper-respiratory-tract infection, and increased clotting time.