Eculizumab Overview

Introduction of Eculizumab

Eculizumab (trade name Soliris) is a recombinant humanized monoclonal antibody produced by murine myeloma cell culture and purified by standard bioprocess technology. Eculizumab contains human constant regions from human IgG2 sequences and human IgG4 sequences and murine complementarity-determining regions grafted onto the human framework light- and heavy-chain variable regions. Eculizumab is composed of two 448 amino acid heavy chains and two 214 amino acid light chains and has a molecular weight of approximately 148 kDa. This drug is a monoclonal antibody directed against the complement protein C5. This antibody blocks the cleavage of C5 and halts the process of complement-mediated cell destruction. Eculizumab is a product of Alexion Pharmaceuticals and has been shown to be effective in treating paroxysmal nocturnal hemoglobinuria. In March 2007, eculizumab was approved by the FDA as a treatment for adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AchR) antibody-positive. In the Phase 3 REGAIN study and its ongoing open-label extension study, Soliris demonstrated treatment benefits for patients with anti-AchR antibody-positive gMG.

Mechanism of Action of Eculizumab

Myasthenia gravis (MG) is a debilitating, chronic and progressive autoimmune neuromuscular disease that can occur at any age. It typically begins with weakness in the muscles that control the movements of the eyes and eyelids, and often progresses to the more severe and generalized form, known as gMG, with weakness of the head, neck, trunk, limb and respiratory muscles. A genetic mutation in paroxysmal nocturnal hemoglobinuria (PNH) patients leads to the generation of populations of abnormal RBCs (known as PNH cells) that are deficient in terminal complement inhibitors (CD-59), rendering PNH RBCs sensitive to persistent terminal complement-mediated destruction. The destruction and loss of these PNH cells (intravascular hemolysis) results in low RBC counts (anemia) and also fatigue, difficulty in functioning, pain, dark urine, shortness of breath, and blood clots. Soliris® is a complement inhibitor that works by inhibiting the terminal part of the complement cascade, a part of the immune system that, when activated in an uncontrolled manner, plays a role in serious ultra-rare disorders like paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS) and anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG). Eculizumab, the active ingredient in Soliris, is a monoclonal antibody that binds to the complement protein C5 specifically and with high affinity, thereby inhibiting its cleavage to C5a and C5b and subsequent generation of the terminal complement complex C5b-9. This interference prevents the destruction of red blood cells (hemolysis) and therefore results in stabilization of hemoglobin and a decrease in the need for blood transfusions in persons with paroxysmal nocturnal hemoglobinuria (PNH). Soliris inhibits terminal complement mediated intravascular hemolysis in PNH patients and therefore the destruction of PNH erythrocytes that lack complement protection with CD-59.

Fig.1 Mechanism of action of Eculizumab

Table 1. Clinical Projects of Eculizumab*

Table 2. Approved Drugs of Eculizumab**

INN (trade name)	Therapeutic area	Dose	Strength	Route	Company	Marketing start	Market
Soliris	paroxysmal nocturnal hemoglobinuria (PNH)	Solution for injection	300 mg / vial	Intravenous infusion	ALEXION PHARM	March 16 2007

What We Provide

Therapeutic Antibody

Eculizumab

We provide high-quality Eculizumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?term=Eculizumab

** Information presented in the table were collected from the following website:
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&;ApplNo=125166

For research use only. Not intended for any clinical use.