Soliris is the first therapy approved for paroxysmal nocturnal hemoglobinuria (PNH), a rare, disabling and life-threatening blood disorder defined by chronic red blood cell destruction, or hemolysis. Soliris is FDA indicated for the treatment of patients with PNH to reduce hemolysis and it was approved on March 16th of 2007.
Soliris has proven to be a safe and effective therapy for PNH in three multi-national clinical studies: TRIUMPH, a placebo-controlled 26 week Phase 3 study involving 87 PNH patients,(5) SHEPHERD, an open-label 52 week Phase 3 trial involving 97 PNH patients,(6) and E05-001, a long term extension study.(7) These studies showed that Soliris reduced hemolysis in every treated patient. Hemolysis was dramatically reduced from a baseline LDH of 2,032 U/L to 239 U/L at week 26 (p<0.001). The reductions in hemolysis occurred within one week of initiating treatment and were sustained for periods of up to 54 months with continued dosing of Soliris. The reduction in hemolysis expands the number of circulating PNH cells and, thereby, increases the hemoglobin level. Hemoglobin stabilization and the number of transfused packed red blood cell units, the pivotal study’s co-primary endpoints, were both achieved; half of the Soliris-treated patients achieved hemoglobin stabilization compared with none of the patients in the placebo group, the median number of transfusions was reduced from 10 units/patient to 0 units/patient, respectively (p < 0.001 in both cases). Soliris patients reported less fatigue and improved health-related quality of life. There were fewer thrombotic events with Soliris treatment than during the same period of time prior to treatment.
Total duration of treatment with Soliris has not been determined . In the HUS studies, patients were treated for median of 40 weeks, with some treated beyond 60 weeks. Etiological basis of disease in both HUS and PNH suggests that the treatment should be prolonged. Retrospective reviews of experience suggest improved survival for prolonged treatment and at this point results for treatment of longer than a year are beginning to be published.
Under the Food and Drug Administration Amendments Act of 2007, FDA has determined that a REMS is necessary for the benefits of Soliris to outweigh the risks of the product. The REMS will include a Medication Guide for patients and requires that all prescribers and patients enroll in a special program to track the long term safety of Soliris therapy.
A Risk Evaluation and Mitigation Strategy (REMS) is a strategy to manage known or potential serious risks associated with a drug product and is required by the Food and Drug Administration to ensure that the benefits of the drug outweigh its risks.
The goals of the Soliris REMS, the OneSource Safety Support Program, are:
- To mitigate the occurrence and morbidity associated with meningococcal infections
- To inform and educate Healthcare Professionals (HCP) and Patients (or Caregivers, or Legal Guardians) regarding:
- the increased risk of meningococcal infections with Soliris
- the early signs of invasive meningococcal infections, and
- the need for immediate medical evaluation of signs and symptoms consistent with possible meningococcal infections.
R. J. Kelly, A. Hill, L. M. Arnold, G. L. Brooksbank, S. J. Richards, M. Cullen, L. D. Mitchell, D. R. Cohen, W. M. Gregory, P. Hillmen. (2011) Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood 117:25, 6786-6792
Alexander Röth, Ulrich Dührsen. (2011) Treatment of paroxysmal nocturnal hemoglobinuria in the era of eculizumab. European Journal of Haematology 87:6, 473-479
Kate McKeage. (2011) Eculizumab. Drugs 71:17, 2327-2345
Young N, Antonioli E, Rotoli B, et al. Safety and efficacy of the terminal complement inhibitor eculizumab in patients with paroxysmal nocturnal hemoglobinuria: SHEPHERD phase III clinical study results. Blood 2006; 108:971.
Hillmen P, Muus P, Duhrsen U, et al. The terminal complement inhibitor eculizumab reduces thrombosis in patients with paroxysmal nocturnal hemoglobinuria. Blood 2006; 108:123.
Soliris(TM) (eculizumab) prescribing information. Alexion Pharmaceuticals, Inc.