Zilucoplan

Summary

Zilucoplan is a synthetic macrocyclic peptide inhibitor of complement C5, approved for the treatment of generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody-positive. It is self-administered subcutaneously once daily.

Mechanism of Action

Selectively binds complement component C5, preventing its cleavage into C5a and C5b, thereby inhibiting the terminal complement cascade and membrane attack complex (MAC) formation.

Routes of Administration

Goals & Uses

• Complement inhibitionImmunology/inflammationHigh
• Reduction of neuromuscular junction damageNeuroprotectionHigh
• Treatment of generalized myasthenia gravis (gMG)Neuromuscular DiseaseHigh

Contraindications

• Lack of meningococcal vaccination prior to initiationInfection PreventionHigh
• Unresolved Neisseria meningitidis infectionInfectious DiseaseHigh

Adverse Effects

• Injection site reactionsLocalCommon
• HeadacheNeurologicCommonPain in the head or upper neck
• Serious infections (meningococcal)InfectionRare
• Upper respiratory tract infectionInfectiousCommon
• DiarrheaGastrointestinalCommonLoose or frequent stools

Drug Interactions

• Live vaccinesModerate
• Other immunosuppressantsModerate

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric patientsAgeRelative
• Patients with active systemic infectionsInfectious DiseaseRelative

Regulatory Status

• European UnionApprovedApproved: Generalized myasthenia gravis in adults who are anti-AChR antibody-positiveEuropean Medicines Agency (EMA) approved in 2023.
• United StatesApprovedApproved: Generalized myasthenia gravis (gMG) in adults who are anti-AChR antibody-positiveFDA approved October 17, 2023; brand name Zilbrysq; carries boxed warning for meningococcal infections.
• United KingdomApprovedApproved: Generalized myasthenia gravis in adults who are anti-AChR antibody-positiveMHRA approval granted in 2023.

FDA approved in October 2023 (brand name Zilbrysq) for adults with anti-AChR antibody-positive gMG. Approved under the brand Zilbrysq by UCB Pharma. Also received approval in the EU and Japan in 2023.

Evidence & Sources

No sources recorded yet.