FDA Approves First 20% Subcutaneous Immunoglobulin for Primary Immunodeficiency

Yael Waknine

March 05, 2010

March 5, 2010 — The US Food and Drug Administration (FDA) has approved the first 20% subcutaneous formulation of immune globulin liquid (Hizentra, CSL Behring) to prevent infection in patients diagnosed with primary immunodeficiency.

Although intravenous immunoglobulins have been the mainstay of primary immunodeficiency therapy since the 1980s, many patients have difficulty tolerating the infusions because of serious adverse events or poor veins. The subcutaneous formulation allows patients to self-administer weekly infusions, using a small portable pump. Stabilization with L-proline also allows room-temperature storage, eliminating the need for refrigeration.

"With its high concentration, Hizentra is a welcome new [subcutaneous immunoglobulin] treatment option for patients managing primary immunodeficiencies," said John Sleasman, MD, in a company news release. "Hizentra's ready-to-use attribute will allow patients to infuse the product where and when it suits them, and physicians now have another product to select to best meet the individual needs of their patients."

Dr. Sleasman is professor and chief of the Division of Allergy, Immunology and Rheumatology at the University of South Florida College of Medicine, Department of Pediatrics, Tampa, and one of the investigators for the company's clinical study that led to product approval.

For the open-label, single-arm study, adult and pediatric patients previously receiving treatment with standard intravenous immunoglobulin every 3 or 4 weeks were switched to weekly doses of the 20% subcutaneous formulation during a 3-month wash-in/wash-out period, followed by a 1-year treatment period.

Results showed that 20% subcutaneous immunoglobulin was efficacious for preventing infections (annual rate, 2.76 infections/patient year), antibiotic use for treatment/prevention of infection (48.5 days/patient year), days out of work or school resulting from infections (2.06 days/patient year), and infection-related hospitalizations (0.2 days/patient year); no serious bacterial infections were reported.

Adverse events most commonly (≥5%) included injection-site reactions, headache, vomiting, pain, and fatigue.

Subcutaneous immune globulin therapy is contraindicated in patients with a history of anaphylactic or severe systemic response to immune globulins or product components such as polysorbate 80, and in those with selective immunoglobulin A deficiency with immunoglobulin A antibodies and a history of hypersensitivity. Because L-proline is used as a stabilizer, the product should not be used in patients with hyperprolinemia.

Patients should be monitored for reactions to intravenous immunoglobulins that may also occur with the subcutaneous formulation, including renal dysfunction/failure, thrombotic events, aseptic meningitis syndrome, hemolysis, and transfusion-related acute lung injury.

As with other products derived from human plasma, the risk for transmission of infectious agents (and theoretically, the Creutzfeldt-Jakob disease agent) cannot be completely eliminated.