Zilucoplan

Neurology / Autoimmune

Also known as: Zilbrysq, RA101495, Zilucoplan Injection

Complement Inhibitors (Macrocyclic Peptide)Research phase: FDA-approvedRegulatory: FDA-approved (2023) for generalized myasthenia gravis in anti-AChR antibody-positive adults (Zilbrysq). Daily subcutaneous self-injection.

Mechanism

Zilucoplan is a self-injectable macrocyclic peptide that blocks complement C5, preventing the formation of the membrane attack complex (MAC) that damages tissues. It is FDA-approved for generalized myasthenia gravis (gMG) — an autoimmune disease where antibodies against the neuromuscular junction activate complement, destroying the junction and causing muscle weakness. Zilucoplan is notable for being a small synthetic peptide complement inhibitor rather than a large monoclonal antibody.

Technical detail

Zilucoplan is a 15-amino-acid macrocyclic peptide (molecular weight ~3.5 kDa) with a PEG tail, that binds complement C5 with high affinity, preventing its cleavage by C5 convertase into C5a (potent anaphylatoxin/chemoattractant) and C5b (initiator of C5b-9 MAC assembly). In anti-AChR antibody-positive gMG, complement activation at the neuromuscular junction deposits MAC on postsynaptic membranes, destroying AChR-rich folds. Zilucoplan preserves proximal complement function (C3b opsonization) while blocking terminal pathway. Self-administered daily SC injection. Requires meningococcal vaccination due to C5 inhibition.

Build a personalized protocol with Zilucoplan →