Eculizumab

Title: Eculizumab
CAS Registry Number: 219685-50-4
CAS Name: Anti-(human complement C5a-chain)(human-mouse monoclonal 5G1.1 heavy chain)immunoglobulin, disulfide with human-mouse monoclonal 5G1.1 light chain, dimer
Additional Names: h5G1.1 Fab; h5G1.1VHC + h5G1.1VLC
Literature References: Humanized monoclonal antibody directed against complement component C5; designed to prevent activation of complement-mediated inflammation and tissue injury. Prepn: M. J. Evans et al., WO 9529697; eidem, US 6355245 (1995, 2002 both to Alexion); and complement inhibition study: T. C. Thomas et al., Mol. Immunol. 33, 1389 (1996). Clinical evaluation in paroxysmal nocturnal hemoglobinuria: P. Hillmen et al., N. Engl. J. Med. 350, 552 (2004); A. Hill et al., Blood 106, 2559 (2005). Review of development and therapeutic potential: M. Kaplan, Curr. Opin. Invest. Drugs 3, 1017-1023 (2002).
Therap-Cat: Anti-inflammatory.
Keywords: Anti-inflammatory (Biological Response Modifier).
Edatrexate Edestin Edifenphos Edifoligide Sodium Edotecarin

Eculizumab ?
Monoclonal antibody
Type Whole antibody
Source Humanized (from mouse)
Target Complement protein C5
Clinical data
Trade names Soliris
AHFS/Drugs.com monograph
Licence data EMA:Link, US FDA:link
Pregnancy cat. C (US)
Legal status POM (UK) -only (US)
Routes Intravenous infusion
Pharmacokinetic data
Half-life 8 to 15 days (mean 11 days)
Identifiers
CAS number 219685-50-4 YesY
ATC code L04AA25
DrugBank DB01257
UNII A3ULP0F556 YesY
ChEMBL CHEMBL1201828 N
Chemical data
Formula  ?
Mol. mass 148 kDa
 N (what is this?)  (verify)

Eculizumab (INN and USAN; trade name Soliris) is a humanized monoclonal antibody that is a first-in-class terminal complement inhibitor and the first therapy approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), a rare, progressive, and sometimes life-threatening disease characterized by excessive destruction of red blood cells (hemolysis).[1] It costs approximately £245,700 for ongoing treatment, but there is variance depending on clinical response.[2]

Eculizumab also is the first agent approved for the treatment of atypical hemolytic uremic syndrome (aHUS), an ultra-rare genetic disease that causes abnormal blood clots to form in small blood vessels throughout the body, leading to kidney failure, damage to other vital organs and premature death.[3][4]

In clinical trials in patients with PNH, eculizumab was associated with reductions in chronic hemolysis, thromboembolic events, and transfusion requirements, as well as improvements in PNH symptoms, quality of life, and survival.[1][5][6][7] Clinical trials in patients with aHUS demonstrated inhibition of thrombotic microangiopathy (TMA),[8] the formation of blood clots in small blood vessels throughout the body,[1][4][5] including normalization of platelets and lactate dehydrogenase (LDH), as well as maintenance or improvement in renal function.[8]

Eculizumab was discovered and developed by Alexion Pharmaceuticals and is manufactured by Alexion. It was approved by the United States Food and Drug Administration (FDA) on March 16, 2007 for the treatment of PNH, and on September 23, 2011 for the treatment of aHUS. It was approved by the European Medicines Agency for the treatment of PNH on June 20, 2007, and on November 24, 2011 for the treatment of aHUS. Eculizumab is currently being investigated as a potential treatment for other severe, ultra-rare disorders.