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Eculizumab is a humanized monoclonal antibody indicated for the treatment of paroxysmal nocturnal haemoglobinuria (PNH). It binds specifically and with high affinity to the complement protein C5, thereby preventing the formation of the terminal complement complex C5b-9, which mediates cell lysis. In patients with PNH, eculizumab inhibits terminal complement mediated intravascular haemolysis.
In clinical trials of PNH patients, eculizumab reduced intravascular haemolysis compared with baseline and placebo, as determined by significantly decreased lactate dehydrogenase (LDH) levels. Significant reductions in LDH levels were achieved within the first week of treatment, with near normal levels achieved at week 2 and maintained throughout longer term treatment, including periods of up to 36 months. Eculizumab achieved rapid and sustained efficacy, regardless of baseline LDH levels or platelet counts.
In adults with PNH, eculizumab treatment for 26 weeks achieved stabilization of haemoglobin levels in significantly more patients than placebo treatment, and reduced the requirement for packed red cell transfusions to a significantly greater extent than placebo. Half of all patients in the eculizumab group became transfusion independent compared with no patients in the placebo group. Eculizumab was also associated with significant improvements in fatigue and health-related quality-of-life scores in several trials. Over the long term, the survival of PNH patients treated with eculizumab was normalized.
Eculizumab was generally well tolerated in clinical trials of PNH patients, including treatment periods of up to 5.5 years. The risk of Neisseria meningitidis is increased with eculizumab and patients must be vaccinated prior to treatment and monitored throughout.
Thus, eculizumab, the first targeted terminal complement inhibitor, provides an effective and generally well tolerated treatment for PNH patients, who have previously been without adequate treatment options.
- 6.Incidence of VTE and relative risk in PNH vs inherited hypercoagulable states. Cheshire (CT): Alexion Pharmaceuticals Inc., 2011. (Data on file)Google Scholar
- 12.Soliris (eculizumab). Prescribing information [online]. Available from URL: http://www.soliris.net/ [Accessed 2011 Oct5]
- 14.European Medicines Agency. Soliris 300 mg: summary of product characteristics. 2007 [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000791/WC500054208.pdf [Accessed 2011 Sep 18]
- 31.Brodsky RA, de Castro III C, Schrezenmeier H, et al. Long term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal hemoglobinuria (PNH) [abstract no. 4237 plus poster]. 52nd American Society of Hematology (ASH) Annual Meeting; 2010 Dec 4–7; Orlando (FL)Google Scholar
- 40.Kim JS, Lee JW, Yoon S-S, et al. Association between elevated hemolysis at diagnosis and early mortality and risk of thrombosis in paroxysmal nocturnal hemglobinuria (PNH) patients with cytopenia [abstract no. 4241]. 52nd American Society of Hematology (ASH) Annual Meeting; 2010 Dec 4–7; Orlando (FL)Google Scholar
- 41.Lee JW, Jang JH, Lee JH, et al. High prevalence and mortality associated with thromboembolism in Asian patients with paroxysmal nocturnal hemoglobinuria (PNH) [abstract no. 0505]. Haematologica 2010; 95 Suppl. 2: 205Google Scholar
- 48.US National Institutes of Health. Eculizumab pharmacokinetics/pharmacodynamics study in pediatric/adolescent PNH subjects [online]. Available from URL: http://clinicaltrials.gov/ct2/show/NCT00867932 [Accessed 2011 Oct 10]
- 49.Curran KJ, Kernan NA, Prockop SE, et al. Paroxysmal nocturnal hemoglobinuria (PNH) in pediatric patients: review of a single center series [abstract no. 223]. 52nd American Society of Hematology (ASH) Annual Meeting; 2010 Dec 4–7; Orlando (FL)Google Scholar
- 50.Meningitis in PNH patients treated with eculizumab in clinical trials. Cheshire (CT): Alexion Pharmaceuticals Inc., 2011. (Data on file)Google Scholar
- 51.US National Institutes of Health. ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov/ct2/results?term=eculizumab [Accessed 2011 Sep 5]
- 52.Stegall MD, Diwan T, Raghavaiah S, et al. Terminal complement inhibition decreases antibody-mediated rejection in senstitized renal transplant recipients. Am J Transplant. Epub 2011 SepGoogle Scholar