Zilucoplan

Zilucoplan is a synthetic ring-shaped, or macrocyclic, peptide developed as RA101495. It targets complement C5 in generalized myasthenia gravis, an autoimmune disease causing weakness when antibodies damage nerve–muscle communication. Zilbrysq received US approval in 2023 for the anti-AChR-positive adult population.

Binding C5 prevents cleavage into C5a and C5b and blocks formation of the membrane attack complex. In anti-AChR-positive disease, antibodies recruit complement to the neuromuscular junction, damaging the muscle’s receptor-bearing surface. Interrupting that cascade protects the junction from complement injury.

The small peptide can be self-administered subcutaneously each day, unlike intravenous complement therapies. At 12 weeks in Phase 3 RAISE, it significantly improved myasthenia-gravis activities-of-daily-living scores compared with placebo.

FDA approved Zilbrysq in 2023 for generalized myasthenia gravis in adults who test positive for anti-acetylcholine-receptor antibodies. A boxed warning addresses serious meningococcal infection. Meningococcal vaccination and participation in a risk-management program are required.

This is a targeted treatment for anti-AChR-positive adult generalized myasthenia gravis. Once-daily self-injection offers an at-home administration option within the complement-inhibitor class.

Common adverse effects include injection-site reactions or bruising, upper-respiratory infections and diarrhea. Serious meningococcal and other infections are important risks. Labeling also addresses pancreatitis and pancreatic cysts; vaccination and the risk-management requirements remain essential precautions.