Soliris is a monoclonal antibody that specifically binds to the complement protein C5, thus inhibiting terminal complement mediated intravascular hemolysis in PNH patients.
Soliris is specifically indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.
Soliris is supplied in 300 mg single-use vials containing 30 mL of 10 mg/mL sterile solution designed for intravenous infusion.
The recommended initial dose of the drug 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.
FDA approval of Soliris was based on the results of three clinical trials.
This randomized, double-blind, placebo-controlled trial enrolled 87 subjects who had received at least four transfusions in the prior 12 months, had a flow cytometric confirmation of at least 10% PNH cells and platelet counts of at least 100,000/microliter. All subjects received meningococcal vaccination prior to treatment. They were subsequently observed to determine the hemoglobin concentration "set-point" in order to define each patient’s hemoglobin stabilization and transfusion outcomes. The subjects were then randomized to receive placebo or Soliris, via intravenous infusion over 25 - 45 minutes, at 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 26 weeks. Primary endpoints included hemoglobin stabilization, the number of RBC units transfused, fatigue, and health-related quality of life. Results revealed that the subjects treated with Soliris had significantly reduced hemolysis compared to placebo (p< 0.001), resulting in improvements in anemia as indicated by increased hemoglobin stabilization and reduced need for RBC transfusions. After 3 weeks of Soliris treatment, patients reported less fatigue and improved health-related quality of life.
Study 2 and extension study
This randomized, double-blind, placebo-controlled trial enrolled 97 subjects, 96 of whom completed treatment, who had received at least one transfusion in the prior 24 months and with at least 30,000 platelets/microliter. All subjects received meningococcal vaccination prior to treatment followed by Soliris, via intravenous infusion over 25 - 45 minutes, at 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 52 weeks. Concomitant medications included anti-thrombotic agents and systemic corticosteroids. The primary endpoints were the same as in study 1. A reduction in intravascular hemolysis, measured by serum LDH levels, was sustained for the treatment period and resulted in a reduced need for RBC transfusion and less fatigue. The long term study enrolled 187 Soliris treated subjects. A reduction in intravascular hemolysis over a total Soliris exposure time ranging from 10 to 54 months was sustained by all the subjects. In addition, there were fewer thrombotic events with Soliris treatment than during the same period of time prior to treatment. The effects of concomitant anticoagulant therapy withdrawal during Soliris therapy was not studied.
Ongoing Study Commitments
Adverse events associated with the use of Soliris may include, but are not limited to, the following:
Soliris is a is a recombinant humanized monoclonal IgG2/4 antibody produced by murine myeloma cell culture. A genetic mutation in PNH leads to the generation of abnormal red blood cells (RBCs) that are deficient in terminal complement inhibitors, rendering them sensitive to persistent terminal complement-mediated destruction. The destruction and loss of these RBCs leads to the symptoms associated with PNH. The active ingredient in Soliris, eculizumab, specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9. Soliris inhibits terminal complement mediated intravascular hemolysis in PNH patients.
For additional information regarding Soliris or paroxysmal nocturnal hemoglobinuria, please visit the Soliris web page.
The Soliris (eculizumab) drug information shown above is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.