Zilucoplan 23mg/0.574ml solution for injection pre-filled syringes

The complement system is part of the innate immune system and is critical in inflammatory reactions in response to pathogenic bacteria. Activation pathways of the complement system involve the cleavage of the complement protein C5 by C5 convertases to form C5a, a potent anaphylatoxin, and C5b.[A261841][A261851] Cleavage of C5 also recruits C6, C7, C8, and C9. C5b binds to C6 [A261841][A261846] to yield the terminal complement complex C5b9, a hydrophilic pore that spans the cell membrane. C5b9 causes an influx of water and ions, resulting in osmotic lysis of the targeted cell.[A261841][A261851] The terminal complement cascade has been implicated in the pathophysiology of various inflammatory and autoimmune disorders, including gMG. gMG is an autoimmune disorder characterized by pathogenic autoantibodies that bind to AChRs. Accumulated MAC on the postsynaptic plasma membrane of the neuromuscular junction leads to muscle weakness and damage.[A261851]

The exact mechanism of zilucoplan in gMG has not been fully elucidated. Zilucoplan binds to the complement protein C5 with high affinity to inhibit its cleavage to C5a and C5b, preventing the generation of C5b9.[L48516]