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Synonyms: h5G1.1 | h5G1.1VHC | Soliris®
eculizumab is an approved drug (FDA (2011), EMA (2007))
Compound class:
Antibody
Comment: Eculizumab is a humanized monoclonal antibody targeting terminal complement activation, by binding to complement component C5 and inhibiting the production of C5a [4]. It is the first approved therapy for paroxysmal nocturnal hemoglobinuria.
Eculizumab's developers, Alexion Pharmaceuticals have developed a next-generation version of eculizumab called ravulizumab (ALXN1210; FDA approved in December 2018), that has a longer circulating half-life than the originator, which allows for monthly dosing. The evidence confirming C5, C5a and the C5a receptor as anti-inflammatory and anti-cancer drug targets is reviewed by Horiuchi and Tsukamoto (2016) [2]. Biosimilars: Amgen's biosimilar ABP 959 (eculizumab-aeeb; Bekemv®) was approved by the EMA in April 2023. This was approved as an interchangeable biosimilar to Soliris® by the FDA in May 2024. Samsung Bioepis' biosimilar (eculizumab-aagh; SB12; Epysqli®) was approved by the EMA in May 2023, and by the FDA in July 2024. BOW080 (Polpharma Biologics, formerly Epirus Biopharmaceuticals) was in development, but this project appears to have been discontinued. |
| No information available. |
Summary of Clinical Use  |
| Used to treat paroxysmal nocturnal hemoglobinuria (PNH). In the UK, NICE (National Institute for Health and Care Excellence) has approved eculizumab as a treatment for the rare, but fatal blood disorder, atypical haemolytic uraemic syndrome (aHUS). This decision was reached because eculizumab represents a significant innovation for a disease with a high unmet clinical need. Eculizumab treatment is expected to increase life expectancy of aHUS patients by decades. The FDA expanded approval in October 2017, to include treatment of patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AchR) antibody-positive. SARS-C0V-2 and COVID-19: Eculizumab has been entered into clinical trials that aim to determine its ability to combat the dysregulated immune response that drives organ damage (lung and other organs) in patients with severe COVID-19. |
| Mechanism Of Action and Pharmacodynamic Effects |
| This antibody blocks the cleavage of the complement protein C5 and thereby prevents the formation of C5a and the membrane attack complex, which lowers the risk of blood clot formation and intravascular hemolysis, the most common thrombotic complications underlying mortality in PNH patients. Chronic uncontrolled activation of the complement system also plays a major role in the debilitating symptoms and potentially life-threatening complications for anti-AchR antibody-positive gMG patients. Ecilizumab effectively inhibits the terminal complement cascade and directly targets this critical underlying cause of gMG. |
| Clinical Trials | |||||
| Clinical Trial ID | Title | Type | Source | Comment | References |
| NCT04288713 | Eculizumab (Soliris) in Covid-19 Infected Patients | Expanded Access | Hudson Medical | Inhibition of the complement pathway and membrane attack complex formation using eculizumab is being examined as a mechanism to block excessive immune system activation in response to SARS-CoV-2 infection. It is hoped that this strategy will aid recovery from the infection by providing a therapeutic window during which severely affected patients may respond more effectively to supportive medical care. | |
| External links |
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For extended ADME data see the following: Electronic Medicines Compendium (eMC) Drugs.com European Medicines Agency (EMA) |
