Myasthenia Gravis
An autoimmune neuromuscular disorder where antibodies attack acetylcholine receptors at the neuromuscular junction, causing fluctuating muscle weakness. Zilucoplan, a self-administered peptide complement C5 inhibitor, is approved for generalised myasthenia gravis in anti-AChR antibody positive adults.
Technical Context
MG subtypes: AChR antibody-positive (~85% — antibodies cause AChR loss through three mechanisms: complement-mediated membrane destruction/MAC formation, crosslinking-induced AChR internalisation, and direct receptor blockade), MuSK antibody-positive (~5-8% — antibodies disrupt agrin/LRP4/MuSK signalling critical for AChR clustering), LRP4 antibody-positive (~2-3%), and seronegative (~5-10%). Zilucoplan targets the complement-mediated damage mechanism specifically — it blocks C5 cleavage, preventing C5a inflammatory signalling and MAC formation at the NMJ. Approved for generalised MG in anti-AChR antibody-positive adults (the subtype where complement plays the most significant role). Dosing: 0.3mg/kg daily SC self-injection. RAISE Phase III trial: significant improvement in MG-ADL (Myasthenia Gravis Activities of Daily Living) score at week 12 vs placebo. Meningococcal vaccination is required before starting zilucoplan (complement inhibition increases meningococcal infection risk — same requirement as for eculizumab).