Recombinant monoclonal antibody approved for the treatment of paroxysmal nocturnal hemoglobinuria to reduce hemolysis
Soliris Eculizumab ALEXIONRecombinant monoclonal antibody approved for the treatment of paroxysmal nocturnal hemoglobinuria to reduce hemolysis
This recombinant humanized monoclonal antibody binds specifically and with high affinity to the complement protein C5, inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9. Eculizumab prevents terminal complement-mediated intravascular hemolysis. This agent was approved on March 16, 2007, for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.
Efficacy. The efficacy of eculizumab was evaluated in a randomized, double-blind, placebo-controlled, 26-week study (Study 1); in a single-arm, 52-week study (Study 2); and in a long-term extension study. All patients received meningococcal vaccinations before eculizumab treatment. In all trials, the dose of eculizumab (administered as an intravenous infusion over 25–45 minutes) was 600 mg every 7±2 days for 4 weeks, followed by 900 mg 7±2 days later, then 900 mg every 14±2 days for the study duration. In Study 1, patients with PNH who had undergone ≥4 transfusions in the previous 12 months, had flow cytometric confirmation of ≥10% PNH cells, and had platelet counts of ≥100,000/microliter were randomized to receive either eculizumab (n=43) or placebo (n=44). Study end points included the number of patients achieving hemoglobin stabilization, the number of red blood cell units transfused, fatigue, and health-related quality of life. Patients treated with eculizumab had significantly reduced hemolysis (P<.001), resulting in a reduced incidence of anemia (indicated by increased hemoglobin stabilization and reduced need for red blood cell transfusions) versus placebotreated patients. After 3 weeks of eculizumab treatment, patients also reported less fatigue and improved health-related quality of life. In Study 2, patients with PNH who had undergone ≥1 transfusion in the previous 24 months and who had ≥30,000 platelets/microliter received eculizumab for 52 weeks. Of the 97 enrolled patients, 96 completed the study. Eculizumab treatment resulted in a reduction in intravascular hemolysis that was sustained over the treatment period and that reduced both fatigue and the need for red blood cell transfusions. Eculizumab-treated patients (N=187) were also enrolled in a long-termextension study, in which all patients sustained a reduction in intravascular hemolysis over the treatment period (range, 10–54 months).
Dosing. The recommended dose regimen for eculizumab treatment is 600 mg every 7 days for the first 4 weeks, followed by 900 mg for the fifth dose 7 days later, then 900 mg every 14 days thereafter. Eculizumab should be administered at these recommended time points or within 2 days of these time points. Eculizumab must be diluted to a final admixture concentration of 5 mg/mL; the final admixed eculizumab 5-mg/mL infusion volume is 120 mL for 600-mg doses and 180 mL for 900-mg doses. The admixture should be allowed to adjust to room temperature and should then be administered by intravenous infusion over 35 minutes via gravity feed, a syringe-type pump, or an infusion pump.
Pricing. The annual wholesale acquisition cost of eculizumab is expected to be approximately $389,000, or $4,992 per 300-mg vial.