Privigen: New formulation recently approved by FDA for the treatment of primary immunodeficiency and chronic immune thrombocytopenic purpura

September 1, 2007

A new formulation for immune globulin intravenous (human), 10% liquid, a polyvalent human immunoglobulin G approved for the treatment of primary immunodeficiency and chronic immune thrombocytopenic purpura.

Key Points

This formulation of immune globulin intravenous (human) (IGIV) contains a broad spectrum of antibody specificities, thereby allowing abnormally low immunoglobulin G (IgG) levels to be restored to the normal range in patients with primary immunodeficiency (PI). In the treatment of chronic immune thrombocytopenic purpura (ITP), IGIV's mechanism of action is unclear. IgG-induced Fc-receptor blockade of phagocytes may induce a treatment effect by inhibiting the elimination of autoantibody-reacted platelets from the blood circulation; alternatively, anti-idiotypic antibodies in IGIV may cause down-regulation of platelet autoantibody-producing B cells. This agent was approved on July 26, 2007, for the treatment of PI associated with defects in humoral immunity and for the treatment of chronic ITP to rapidly raise platelet counts to prevent bleeding.

Efficacy. To assess the efficacy of this agent for the treatment of PI, a prospective, open-label, single-arm, multicenter study was carried out in patients with PI. Patients (N=80) were treated for 12 months at a 3-week (n=16) or 4-week (n=64) dosing interval. Doses ranged from 200 to 888 mg/kg. The primary end point was annual rate of acute serious bacterial infections per patient per year. Secondary end points included days of work/school/daycare missed or spent unable to perform normal activities due to illness, days of hospitalization, and use of antibiotics. During the study period, the rate of acute serious bacterial infections was 0.08, which met the predefined success rate of <1 acute serious bacterial infection per patient per year; 80% of patients used antibiotics during the study period. Patients missed days of work/school/daycare or spent days unable to perform normal activities due to illness at an annual rate of 8.65 days per patient year, and patients were hospitalized at an annual rate of 2.52 days per patient year. The efficacy of this agent for the treatment of chronic ITP was assessed in a prospective, open-label, single-arm, multicenter study that enrolled 57 patients with chronic ITP and a platelet count ≤203109/L. Patients were treated with a 1-g/kg infusion BID on 2 consecutive days and were observed for 29 days. The primary end point was response rate (defined as the percentage of patients with platelet counts ≥503109 /L within 7 d after the first infusion). Secondary end points included increase in platelet counts and time to reach a platelet count ≥503109/L, the duration of the response, and the regression of hemorrhage in patients who were bleeding at baseline. A total of 46 patients (80.7%) responded to treatment within 7 days after the first infusion; median time to reach this response was 2.5 days. The median duration of platelet response in patients who achieved a response at any time after the first infusion was 15.4 days. A decrease in hemorrhage severity was observed in the skin (31/36 patients), the oral cavity (11/11 patients), and the genitourinary tract (7/9 patients).

Safety. IGIV products have been associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. In patients predisposed to acute renal failure, IGIV should be administered at the lowest practicable infusion rate; renal function and urine output should be monitored in patients at increased risk of developing acute renal failure. Infrequently, aseptic meningitis syndrome has been reported in association with IGIV products. Rarely, IGIV treatment has resulted in hemolysis. Noncardiogenic pulmonary edema and thrombotic events have been reported in patients treated with IGIV. The most common adverse events observed in patients receiving this agent for the treatment of PI include headache, pain, nausea, fatigue, and chills. The most common adverse events observed in patients receiving this agent for the treatment of chronic ITP include headache, pyrexia/hyperthermia, and anemia.