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%).
Treatment of autoimmune disease such as rheumatoid arthritis, membranous nephritis, lupus nephritis, dermatomyositis, and autoimmune hemolytic anemias.
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.
Recombinant monoclonal antibody:
Paroxysmal nocturnal haemoglobinuria (PNH)
Atypical haemolytic uraemic syndrome (aHUS)
Refractory generalized myasthenia gravis (gMG) in
patients who are anti-acetylcholine receptor (AChR)
antibody-positive (MG)
Human antibodies undergo endocytotic digestion in
the cells of the reticuloendothelial system. Eculizumab
contains only naturally occurring amino acids and has
no known active metabolites. Human antibodies are
predominately catabolised by lysosomal enzymes to small
peptides and amino acids.
