Eculizumab
- CAS Number: 219685-50-4
Eculizumab ( Soliris trade name, manufacturer, Alexion ) is a monoclonal antibody for the treatment of paroxysmal nocturnal hemoglobinuria (PNH ) is used.
With annual treatment costs of about € 400,000, it is the most expensive drug in the world (as of 2013).
Mode of action and applications
The Paroxysmal nocturnal hemoglobinuria is a rare acquired clonal and life-threatening disorder of hematopoietic stem cells. PNH patients have a defect in the protein CD59 on the cell surface of blood cells. CD59 serves as an anchor for other protein on the cell surface antigens present. The diagnosis can be made about the detection of a significant proportion of red (erythrocytes) and white blood cells ( monocytes, granulocytes ) which do not have the coupled via this anchor protein antigens. This is done using flow cytometric methods. Clinically relevant is the absence of certain proteins on the surface of red blood cells in PNH. Due to this defect, the red blood cells are attacked by the complement system and give rapidly; This leads to anemia.
Eculizumab acts by binding to the protein of the complement C5 and blocks the activation of so-called terminal. Wherein the destruction of the red blood cells is reduced and the symptoms of the disease are ameliorated.
Eculizumab is approved exclusively for use in paroxysmal nocturnal hemoglobinuria. Eculizumab is administered by intravenous infusion several times a month.
Contraindications and side effects
Eculizumab should not be used in known hypersensitivity to murine proteins or eculizumab. Eculizumab should not be used in patients with known hereditary Komplementdefekt, when not healed infection with Neisseria meningitidis ( meningococcal ) or in the absence of vaccination against Neisseria meningitidis. Neisseria infections are so problematic, because by the mechanism of action of eculizumab the body's defense against these bacteria is limited. Can cause meningococcal meningitis among others. A meningococcal septicemia in two patients was the most serious adverse event during clinical trials with eculizumab. Infusion reactions, which would have required the discontinuation of eculizumab have not yet been observed. A previous vaccination against meningococcal disease is recommended during administration of eculizumab.
The most common side effects are headache, sore throat, nausea, fever, muscle pain, fatigue and herpes simplex.
At about 3.5% of the Japanese population, but also in Han Chinese a heterozygous mutation in the gene for complement factor 5 occurs with a single nucleotide polymorphism ( G2654A ), in which a replacement of the amino acid arginine with histidine at position 885 ( Arg885His ) results in a poor response to eculizumab in therapy paroxysmal nocturnal haemoglobinuria.
Production
Eculizumab is a humanized antibodies of the IgG2 / 4 and is manufactured by Lonza in genetically stable mouse myeloma cell line NS0. Eculizumab was developed by the U.S. biotechnology company Alexion and has been approved since 2007 in the U.S. and in the EU orphan drug. It was in the European Union, the first drug that has been approved through the centralized procedure via an accelerated assessment procedure.
Costs
The price of an infusion bottle (300 mg) is 5827 euros. The maintenance dose is 900 mg eculizumab approximately every 14 days.
Trade names
Eculizumab is available in Germany, Austria and Switzerland under the name of Soliris in the trade.