Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Correction - August 2009
The brand name for eculizumab should be Soliris
30 mL vials containing 10 mg/mL
Approved indication: paroxysmal nocturnal haemoglobinuria
Australian Medicines Handbook Appendix A
Paroxysmal nocturnal haemoglobinuria is a rare cause of haemolytic anaemia. Patients have stem cells with a somatic mutation which results in red blood cells being unable to anchor a complement inhibitory protein to their cell membrane. The absence of this protein makes the affected red blood cells vulnerable to complement-induced haemolysis. This haemolysis results in haemoglobinuria and anaemia. Patients are also prone to thrombosis, and thromboembolism is a common cause of death.
Blocking the action of complement on the abnormal cells could reduce haemolysis. Eculizumab achieves this by binding to complement protein C5.
Eculizumab is a humanised monoclonal mouse antibody (IgG). After infusion over 35 minutes, eculizumab rapidly reduces complement activity. This infusion is given weekly for five weeks and then repeated every two weeks. The half-life of eculizumab is approximately 11 days and maintaining the serum concentration above 35 microgram/mL suppresses haemolysis.
A preliminary study treated 11 patients for 12 weeks. Concentrations of lactate dehydrogenase, a marker of haemolysis, fell after the first dose of eculizumab. Haemolytic activity was completely blocked in patients whose serum concentration remained above 35 microgram/mL.1 These patients continued in a 52-week extension study and nine showed complete blockade of haemolysis throughout. This reduction in haemolysis raised the proportion of affected cells, as a proportion of the total number of red cells, from 37% at baseline to 58% at 64 weeks.2
To investigate the effect of eculizumab on transfusion requirements 87 patients were randomised in a double-blind controlled trial. After 26 weeks haemoglobin concentrations had stabilised in 49% of the patients given eculizumab and 51% had not required a blood transfusion. The haemoglobin did not stabilise in the placebo group and they all needed transfusions. The mean number of units of packed cells used was three in the eculizumab group and 11 in the placebo group. Patients given eculizumab had an improved quality of life.3
An open-label study, with less stringent inclusion criteria, then treated 97 patients for 52 weeks. Haemolytic activity was suppressed in 89 patients throughout the study. The survival of the affected cells increased their proportion in the red cell population from 39% to 55%. Transfusions reduced from an annual mean of 12 units of packed cells to six units. There were 49 patients who did not need a transfusion while being treated with eculizumab.4
During this study the most frequent adverse effects were headache, upper respiratory tract symptoms, nausea and fever. These symptoms tended to be less frequent during the second six months of treatment.4 Infections are common, but usually mild, however eculizumab increases susceptibility to meningococcal infections because of its effect on the complement system. Patients should therefore be given a meningococcal vaccine before starting treatment.
Patients can develop antibodies to eculizumab, but so far these have not reduced the effect of the drug. There is still a potential for infusion reactions.
An analysis of the thromboembolism rate in the studies found that it fell from 7.37 events/100 patient years to 1.07 events/100 patient years with treatment.5 While the reduction is significant, there is not yet enough evidence to change the management of patients being treated with anticoagulants. The effect of eculizumab on survival is currently unknown.
Bone marrow transplantation can cure the condition, but donors are scarce and the procedure has significant risks. Eculizumab can reduce haemolysis, but the outcome of long-term treatment is uncertain. As treatment increases the proportion of affected cells in the circulation, people may have a high risk of serious haemolysis when they stop the drug. While eculizumab will reduce the need for treatments such as transfusion, these savings will not offset the high cost of the drug.
The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
Notes on references
At the time the comment was prepared, information about
this drug was available on the website of the Food and Drug
Administration in the USA (
At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.europa.eu).
- Hillmen P, Hall C, Marsh JC, Elebute M, Bombara MP, Petro BE, et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med 2004;350:552-9.
- Hill A, Hillmen P, Richards SJ, Elebute D, Marsh JC, Chan J, et al. Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria. Blood 2005;106:2559-65.
- Hillmen P, Young NS, Schubert J, Brodsky RA, Soci G, Muus P, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 2006;355:1233-43.
- Brodsky RA, Young NS, Antonioli E, Risitano AM, Schrezenmeier H, Schubert J, et al. Multi center phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood 2008;111:1840-7.
- Hillmen P, Muus P, Dhrsen U, Risitano AM, Schubert J, Luzzatto L, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood 2007;110:4123-8.