Экулизумаб

Описание

Eculizumab, a fully humanized anti-C5 monoclonal antibody, was introduced for treating patients with PNH to reduce hemolysis. It is the first therapy to be approved for this rare and life-threatening form of hemolytic anemia. PNH is a clonal hematopoietic stem-cell disorder that is characterized by the production of abnormal red blood cells (RBCs) with a deficiency of surface proteins that protect the cells against attack by the body’s complement system. Complement-mediated destruction of the susceptible RBCs results in intravascular hemolysis, the primary clinical manifestation in all PNH patients. Previously, patients with PNH have mainly been managed supportively, with red cell transfusions as required, and treatments such as folate and iron supplementation, anticoagulation for thrombotic disease, and the occasional use of steroids during hemolytic crises. Allogenic stem cell transplantation is currently the only curative option for PNH; however, it is associated with significant morbidity and mortality. Eculizumab therapy is aimed at preventing red cell lysis through blockade of complement activation process and the production of the membrane attack complex. Eculizumab specifically binds to the human complement protein C5 with high affinity (IC₅₀ ＝ 2 nM) and inhibits its cleavage to C5a and C5b, which is a key step in the pathway leading to the membrane attack complex C5b-C9.
Eculizumab has been granted orphan drug status from both the FDA and European regulatory agencies.The most serious adverse reaction associated with eculizumab therapy is meningococcal infections. Eculizumab is contraindicated in patients who are not vaccinated against Neisseria meningitidis or who have N. meningitidis infections. The most common adverse reactions with eculizumab include headache (44%), nasopharyngitis (23%), back pain (19%), and nausea (16%).

Использование

Treatment of autoimmune disease such as rheumatoid arthritis, membranous nephritis, lupus nephritis, dermatomyositis, and autoimmune hemolytic anemias.

Общее описание

Eculizumab (Soliris) is a monoclonal antibodythat binds to the terminal complement protein C5 inRBCs. This blocks the cleavage of C5 and halts the processof complement-mediated cell destruction of the RBCs.Eculizumab has been shown to be effective in treating PNHand in March 2007 was approved by the FDA for treatingPNH.