FDA Approves 20% IG Product for Subcutaneous Infusion

Cheryl A. Thompson

BETHESDA, MD 05 March 2010—CSL Behring and FDA announced Thursday that Hizentra, a 20% liquid immune globulin product for s.c. infusion, had been approved for the treatment of primary humoral immunodeficiency.

The company said its use of L-proline to stabilize the high-concentration product allows for storage at room temperatures up to 25 °C.

Vivaglobin, CSL Behring's 16% liquid immune globulin product for s.c. infusion, must be stored at 2–8 °C in a refrigerator.

According to the FDA-approved labeling (PDF) for Hizentra, the first infusion of the product should occur one week after the patient's last infusion of an i.v. immune globulin product. The initial weekly dose of the 20% s.c. immune globulin product is calculated by multiplying the previous i.v. immune globulin dose, in grams, by 1.53 and then dividing the result by the number of weeks between doses of i.v. immune globulin. Subsequent weekly doses should be adjusted on the basis of clinical response and trough serum concentration of immunoglobulin G.

The labeling recommends infusing the product into the abdomen, thigh, upper arm, or lateral hip. Up to four injection sites, at least 2 in apart, should be used simultaneously. For the first infusion, the maximum volume per injection site is 15 mL and the maximum infusion rate per site is 15 mL/hour. After the fourth infusion, the maximum volume per injection site can be 20 mL and, if tolerated, as much as 25 mL. At any time after the first infusion, the infusion rate per injection site can be increased to as much as 25 mL/hour; however, the total infusion rate for all the sites cannot exceed 50 mL/hour.

All 49 patients in the clinical study of the 20% s.c. immune globulin product had some type of local reaction to at least one infusion, the labeling states. One fourth of the patients had a headache attributable to the treatment. All the patients had previously received i.v. immune globulin therapy.

In addition to the contraindications common to i.v. immune globulin products and the older s.c. immune globulin product, the labeling for Hizentra lists hyperprolinemia and anaphylactic or severe systemic reactions to polysorbate 80, a component of the final product.

CSL Behring will supply the new plasma-derived product in single-use vials containing 5, 10, or 20 mL of preservative-free liquid. Each milliliter has 0.2 g of protein.

Spokesman Greg Healy said the company expects to make Hizentra available in April.