MECHANISM OF ACTION

ZILBRYSQ is a first-of-its-kind complement C5 inhibitor approved for the treatment of gMG in adult patients who are anti-AChR Ab+1,2

Golfer.

Complement activation
in gMG

Generalized myasthenia gravis (gMG) is a chronic, unpredictable, autoimmune disease2

In gMG, pathogenic immunoglobulin G (IgG) autoantibodies attack key proteins, most commonly the acetylcholine receptor (AChR), in the neuromuscular junction (NMJ). This prevents AChR binding, reduces receptor density, and activates the complement system.1,2

Complement activation, resulting in the cleavage of C5 into C5a and C5b by C5 convertase.

In anti-AChR antibody positive (Ab+) gMG, binding of pathogenic autoantibodies to the AChR initiates complement activation2

  • Complement activation, resulting in the cleavage of C5 into C5a and C5b by C5 convertase2,6
  • C5a is a potent proinflammatory mediator, while C5b initiates the terminal complement pathway2
Activating the complement system and formation of a MAC.

Formation of the membrane attack complex (MAC) damages the NMJ2

  • Activation of C5b within the complement cascade contributes to MAC formation
  • This leads to the deposition of MAC on the post-synaptic membrane of the NMJ leading to damage and subsequent impaired synaptic transmission

Complement inhibition
with ZILBRYSQ

ZILBRYSQ is a first-of-its-kind small peptide C5 inhibitor for the treatment of anti-AChR Ab+ gMG1,2

ZILBRYSQ provides complement inhibition.

Small macrocyclic peptide2

ZILBRYSQ is a first-of-its-kind, macrocyclic peptide that specifically targets the complement cascade.

Prevents the subsequent assembly of the MAC.

Prevents assembly of MAC2,3

ZILBRYSQ binds to C5 with high affinity and specificity, preventing C5 cleavage into C5a and C5b by C5 convertase. This prevents the subsequent assembly and activity of the MAC, providing complement inhibition.

The precise mechanism through which ZILBRYSQ exerts therapeutic effects in gMG is unknown.1

"By understanding the pathophysiology of gMG, we can see why ZILBRYSQ was designed to specifically target the complement cascade."

Hannah C. Machemehl, MD
Neuromuscular neurologist

ZILBRYSQ Mechanism of Action


ZILBRYSQ Mechanism of Action (MOA) video

 

See how ZILBRYSQ, a C5 inhibitor, specifically targets the complement cascade, preventing the assembly and activity of the membrane attack complex.1,2

The precise mechanism through which ZILBRYSQ exerts therapeutic effects in gMG is unknown.1

ZILBRYSQ: A Targeted Choice
How ZILBRYSQ specifically targets the complement cascade

 

Watch Dr Hannah Machemehl, an expert in gMG, discuss how ZILBRYSQ provides complement inhibition.

The precise mechanism through which ZILBRYSQ exerts therapeutic effects in gMG is unknown.1

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References:

  1. ZILBRYSQ [Prescribing Information]. Smyrna, GA: UCB, Inc.
  2. Howard JF Jr, Bresch S, Genge A, et al; RAISE Study Team. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, Phase 3 study. Lancet Neurol. 2023;22(5):395-406. doi:10.1016/S1474-4422(23)00080-7
  3. Mantegazza R, Vanoli F, Frangiamore R, et al. Complement inhibition for the treatment of myasthenia gravis. ImmunoTargets Ther. 2020;9:317-331. doi:10.2147/ITT.S261414