Pexelizumab

Summary

Pexelizumab is an anti-C5 complement inhibitor developed by Alexion Pharmaceuticals that was investigated for reducing myocardial injury during cardiac surgery (CABG and PCI) and acute myocardial infarction. Despite promising phase II results, it failed to meet primary endpoints in large phase III trials (PRIMO-CABG II, APEX-AMI) and was not approved by regulatory authorities.

Mechanism of Action

Pexelizumab is a humanized single-chain antibody fragment (scFv) that selectively binds to complement component C5, preventing its cleavage into C5a and C5b. This inhibits the terminal complement pathway, blocking formation of the membrane attack complex (MAC) and reducing complement-mediated inflammation and tissue injury.

Routes of Administration

Goals & Uses

• Reduction of myocardial injury post-CABGCardioprotectionModerate
• Complement inhibition during cardiopulmonary bypassInflammatory ModulationModerate
• Reduction of infarct size in STEMI/AMIAcute Myocardial InfarctionLow

Contraindications

• Unvaccinated patients (meningococcal)Infectious DiseaseHigh
• Active Neisseria meningitidis infectionInfectious DiseaseHigh

Adverse Effects

• Increased susceptibility to encapsulated bacterial infectionsImmunologicalUncommon
• HeadacheNeurologicCommonPain in the head or upper neck
• Infusion-related reactionsHypersensitivityUncommon

Drug Interactions

• Other immunosuppressantsModerate

Population Constraints

• Pregnant womenReproductiveRelative
• Patients with complement deficienciesImmunologicalRelative

Regulatory Status

• European UnionUnapprovedEMA approval never granted; program discontinued.
• United StatesUnapprovedFDA approval never granted; development discontinued after phase III failures.

Pexelizumab was never approved by the FDA or EMA. Development was discontinued following failure in pivotal phase III trials. No current active regulatory status in any major jurisdiction.

Evidence & Sources

No sources recorded yet.