Eculizumab

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Eculizumab
Mass / length primary structure 148  kDa
Identifier
External IDs
Drug information
ATC code L04 AA25
DrugBank DB01257
Drug class monoclonal antibody

Eculizumab (trade name Soliris ; manufacturer Alexion ) is a monoclonal antibody that is used to treat paroxysmal nocturnal hemoglobinuria (PNH).

Mode of action and areas of application

Paroxysmal nocturnal hemoglobinuria is a rare clonal acquired and life-threatening disorder of hematopoietic stem cells . PNH patients have a defect in the CD59 protein on the cell surface of the blood cells. CD59 serves as an anchor protein for other antigens present on the cell surface . The diagnosis can be made via the detection of a significant proportion of red ( erythrocytes ) and white blood cells ( monocytes , granulocytes ) that do not have the antigens coupled via this anchor protein. This is done with the help of flow cytometric methods. Clinically relevant in PNH is the lack of certain proteins on the surface of erythrocytes . As a result of this defect, the red blood cells are attacked by the complement system and broken down too quickly; this leads to anemia .

Eculizumab works by binding to protein C5 of the complement system and blocking what is known as terminal activation. This will reduce erythrocyte destruction and relieve the symptoms of the disease.

Eculizumab was originally only approved for use in paroxysmal nocturnal hemoglobinuria, but has now also been used for the treatment of (atypical) hemolytic uremic syndrome (aHUS) and, since August 2019, for the treatment of neuromyelitis optica spectrum diseases with AQP4 antibodies and an existing push activity. Eculizumab is given by intravenous infusion several times a month.

Eculizumab was successfully used in patients who fell ill with the haemolytic-uremic syndrome caused by the EHEC pathogen in May 2011 and did not respond to treatment with hemodialysis and plasmapheresis . An accompanying, non-randomized study without a control group has not yet been completed in autumn 2011. Due to the current development of EHEC infections, the German Society for Nephrology issued a press release on May 30, 2011 in which the therapy with eculizumab is named as a so-called "rescue medication" in the event of failure of the usual therapy procedures, with the express note that the benefit and risk in this area of ​​application could not be reliably estimated at the time.

Contraindications and side effects

Eculizumab should not be used in cases of known hypersensitivity to eculizumab or to murine proteins. Eculizumab must not be used in patients with a known hereditary complement defect, if the infection with Neisseria meningitidis (meningococci) has not healed or if there is no vaccination against Neisseria meningitidis . Neisseria infections are so problematic because the mechanism of action of eculizumab limits the body's defense against these bacteria. Can meningococcal among others meningitis cause. Meningococcal septicemia in two patients was the most serious adverse event during the eculizumab clinical trials. Infusion reactions that would have required discontinuation of eculizumab have not been observed. Prior vaccination against meningococci is recommended when eculizumab is administered.

The most common side effects are headache, strep throat, nausea, fever, muscle pain, fatigue, and the appearance of herpes simplex .

About 3.5% of the Japanese population, but also of Han Chinese, have a heterozygous mutation of the gene for complement factor 5 with a single nucleotide polymorphism (G2654A) in which the amino acid arginine is replaced by histidine at position 885 ( Arg885His) leads to a poor response to eculizumab in the treatment of paroxysmal nocturnal hemoglobinuria .

Manufacturing

Eculizumab is a humanized IgG 2/4 antibody and is genetically engineered by Lonza in the stable mouse myeloma cell line NS0. Eculizumab was developed by the American biotechnology company Alexion and has been approved as an orphan drug in the US and the European Union since 2007 . It was the first medicinal product in the European Union to be authorized in the centralized procedure via an accelerated assessment procedure.

costs

The price for an infusion bottle (300 mg) is around 5,880 EUR. The maintenance dose for PNH is 900 mg eculizumab approx. Every 14 days, for atypical HUS it is even 1200 mg. This results in costs of over 600,000 EUR per year and that with a lifelong treatment period.

With annual therapy costs of up to EUR 600,000, it was considered the most expensive drug in the world in 2013.

Trade names

Eculizumab is commercially available in Germany, Austria and Switzerland under the name Soliris .

See also

Web links

Individual evidence

  1. ↑ Patient education about treatment with Soliris (eculizumab). In: Competence Network Multiple Sclerosis. Competence Network Multiple Sclerosis, accessed on June 19, 2020 .
  2. ↑ EHEC: Numbers, a Hypothesis and Horror . In: Ärzte Zeitung , November 14, 2011. Archived from the original on May 21, 2014. Retrieved on July 18, 2012. 
  3. ↑ Anne-Laure Lapeyraque, et al .: eculizumab in Severe Shiga toxin-associated HUS. In: New England Journal of Medicine. 364, 2011, pp. 2561-2563, doi: 10.1056 / NEJMc1100859 .
  4. ↑ Press release of the German Society for Nephrology of May 30, 2011. Archived from the original on May 30, 2011 ; Retrieved May 31, 2011 .
  5. ↑ Deutsches Ärzteblatt on eculizumab, March 20, 2007 ( memento of October 19, 2011 in the Internet Archive ). Retrieved May 31, 2011.
  6. ↑ Gensthaler, Siebenandt Eculizumab and Temsirolimus , Pharmazeutische Zeitung, No. 2, 2008 , accessed May 31, 2011.
  7. ↑ Jun-ichi Nishimura, Masaki Yamamoto, Shin Hayashi, Kazuma Ohyashiki, Kiyoshi Ando, ​​Andres L. Brodsky, Hideyoshi Noji, Kunio Kitamura, Tetsuya Eto, Toru Takahashi, Masayoshi Masuko, Takuro Matsumoto, Yuji Wano, Tsutomu, Shichiko Shibay Masakazu Hase, Lan Li, Krista Johnson, Alberto Lazarowski, Paul Tamburini, Johji Inazawa, Taroh Kinoshita, Yuzuru Kanakura: Genetic Variants in C5 and Poor Response to Eculizumab New England Journal of Medicine 2014, Volume 370, Issue 7 of February 13, 2014 , Pages 632-639; doi: 10.1056 / NEJMoa1311084 .
  8. ↑ https://www.fachinfo.de/pdf/010559
  9. ^ Siegfried Hofmann, Holger Alich: Appetite for the most expensive drug in the world . In: Handelsblatt . No. 134 , July 16, 2013, p. 15 .
  10. ↑ Rote Liste Service GmbH (Ed.): Rote Liste 2017 - drug directory for Germany (including EU approvals and certain medical devices) , Rote Liste Service GmbH, Frankfurt / Main, 2017, edition 57, ISBN 978-3-946057-10 -9 , p. 179.