Soliris (eculizumab)Company: Alexion
Approval Status: Approved March 2007
Treatment for: paroxysmal nocturnal hemoglobinuria
Areas: Cardiovascular / Cardiology; Hematology
Possible similar drugs: Soliris
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
- Alexion has agreed to evaluate long-term safety of eculizumab by analyzing outcomes in the Soliris Safety Registry for a time period of no less than five years. At the end of the five year period, a study report will be submitted to the Biological License Application (BLA) that describes the major safety findings from the registry program, including the specific items listed below and proposing labeling changes as appropriate. Additionally, annual interim reports will be submitted to the BLA, along with expedited reports as specified below. All patients within the registry will be followed for the occurrence of: (A) Serious infections, defined as infections necessitating or prolonging hospitalization or resulting in death. Alexion commits to collecting follow-up information from these patients to assess the nature of the serious infection, the duration of hospitalization, the major features of the clinical course and the survival status. Expedited reporting (15 day telephone or facsimile Medwatch communication) will be provided for the occurrence of these serious infections. (B) Malignancy, including the nature of the malignancy and the survival status of the patients who develop a malignancy. (C) Use of eculizumab among pediatric patients under 16 years of age, to include collection of eculizumab dosage information, as well as the same information being required for adult patients in the registry. (D) Pregnancy, including the clinical course of each pregnancy and the detection of congenital abnormalities among babies born to the women exposed to eculizumab during the pregnancy. (E) Thrombotic events, including the nature of the event, the clinical outcome as well as the antocoagulant management prior to and after the event.
Protocol Submission: May 2007
Final Report Submission: June 2012
- Alexion has agreed to conduct a randomized, controlled clinical study to assess the effects of anticoagulant withdrawal among PNH patients receiving eculizumab. This study will randomize at least 100 anticoagulated patients to either continue or discontinue anticoagulation therapy. The major outcomes will assess the safety of discontinuation of anticoagulant therapy while continuing eculizumab, especially with respect to providing important evidence regarding major bleeding and that this discontinuation does not increase the risk for occurrence of thrombotic events in these patients. A full study report and data from this study will be submitted to the BLA and may include a label revision, contingent upon the importance of these study results.
Protocol Submission: June 2007
Study Start June 2009
Final Report Submission: March 2014
Adverse events associated with the use of Soliris may include, but are not limited to, the following:
- Viral Infection
- Back pain
Mechanism of Action
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.
Hillmen P, Young NS, Schubert J, Brodsky RA, Socie G, Muus P, Roth A, Szer J, Elebute MO, Nakamura R, Browne P, Risitano AM, Hill A, Schrezenmeier H, Fu CL, Maciejewski J, Rollins SA, Mojcik CF, Rother RP, Luzzatto L The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. The New England Journal of Medicine 2006 Sep 21;355(12):1233-43.
Hill, A Eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Clinical advances in hematology & oncology : H&O 2005 Nov;3(11):849-50.
Hill A, Hillmen P, Richards SJ, Elebute D, Marsh JC, Chan J, Mojcik CF, Rother RP Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria. Blood 2005 Oct 1;106(7):2559-65. Epub 2005 Jun 28.
Hillmen P, Hall C, Marsh JC, Elebute M, Bombara MP, Petro BE, Cullen MJ, Richards SJ, Rollins SA, Mojcik CF, Rother RP Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. The New England Journal of Medicine 2004 Feb 5;350(6):552-9.
For additional information regarding Soliris or paroxysmal nocturnal hemoglobinuria, please visit the Soliris web page.
Soliris Drug Information
The Soliris 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.