Eculizumab

Compound Name:EculizumabMolecular Target:complement protein C5Molecular Structure:humanizedLicensed Indication:Paroxysmal nocturnal hemoglobinuriaManufacturer and/or Distributor:Alexion PharmaceuticalsInitial FDA Approval2011SummaryEculizumab (Soliris) is a recombinant humanized IgG2/4κ monoclonal antibody that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and blocking the generation of the terminal complement cascade C5b-9. It is administered intravenously, initially once a week. Eculizumab was approved by the FDA in 2007 for treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce terminal complement-mediated intravascular hemolysis. It was shown to reduce or eliminate the need for transfusion, and to improve anemia, fatigue, and the quality of life. In 2011, it received accelerated approval for pediatric and adult patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA). Patients with aHUS who were treated with eculizumab showed improvement in renal function, normalization of hematologic parameters, and elimination of the requirement for plasma therapy. As of October 2014, eculizumab has been granted orphan drug status for the prevention of delayed graft function in renal transplant patients, myasthenia gravis and neuromyelitis optica. Clinical trials are underway for use of eculizumab in myasthenia gravis, Guillain- Barre Syndrome and liver and intestinal transplantation. The most significant safety concern with eculizumab is infection, particularly with meningococcus (Neisseria meningitidis). It is thus contraindicated in patients with unresolved serious Neisseria meningitidis infection. Patients should be vaccinated with a meningococcal vaccine at least two weeks prior to initiating therapy with eculizimab, unless the risks of delaying treatment outweigh the risks of developing a meningococcal infection. Eculizimab may cause also serious allergic reactions. Its use in pregnancy, based on animal data, may cause fetal harm, and caution should be exercised when administered to a nursing woman. However, an international report assessing the safety and efficacy of eculizumab in pregnant women [75 pregnancies in 61 women], concluded that eculizumab was safe and effective with no maternal deaths, 3 fetal deaths [4%] and 6 miscarriages [8%] during the first trimester. Two thrombotic events occurred post-partum. Twenty cord blood samples were submitted for the presence of eculizumab and which was found in 7. Twenty-five babies were breast-fed and of 10 breast milk samples submitted for analysis, none contained eculizumab. Eculizumab is one of the most expensive medications in the world at over $440,000 per year and over $700,000 per year in Canada. Analysis done in Canada and New Zealand suggest the price charged substantially exceeds its cost effectiveness. Biosimilars are not expected to reach the market until 2019.References

Package Insert: http://www.soliris.net/indications/soliris_pi.pdf



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8. Herper M. The World’s Most Expensive Drugs. Forbes. 2010 Feb 19. http://www.forbes.com/2010/02/19/expensive-drugs-cost-business-healthcare-rare-diseases.html

9. Kelly RJ, Hochsmann B, Szer J et al. Eculizumab in Pregnant Patients with Paroxysmal Nocturnal Hemoblobinuria. NEJM 2015; 373:1032 – 1039. http://www.nejm.org/doi/full/10.1056/NEJMoa1502950

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11. Wilson HJ, Jacobs BC,Van Dorn PA.  Gullain-Barre  Syndrome.  Lancet 2016; 388: 717 – 727. http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)00339-1.pdf

12. Petit LM, Rabant M, Canioni D, Suberbielle-Boissel C, Goulet O, Chardot C, Lacaille F. Pediatr Transplant. 2017 Jan 13. doi: 10.1111/petr.12847. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28084679

13. Howard JF Jr, Freimer M, O'Brien F et al. QMG and MG-ADL Correlations: Study of Eculizumab Treatment of Myasthenia Gravis. Muscle Nerve. 2016 Dec 23. doi: 10.1002/mus.25529. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28010051

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