Pexelizumab
Also known as: 5G1.1-scFv, Alexion anti-C5 scFv, h5G1.1-scFv
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Summary
Pexelizumab is a recombinant humanized single‑chain antibody fragment (scFv) that blocks complement component C5. Developed by Alexion for cardiovascular use, it was investigated as an adjunct in coronary artery bypass graft (CABG) surgery and acute myocardial infarction (MI) to reduce reperfusion‑related injury. The compound never achieved regulatory approval and has been withdrawn from development, remaining in the research domain.
Mechanism of Action
Pexelizumab binds to the native C5 protein, preventing its proteolytic cleavage into the pro‑inflammatory fragment C5a and the membrane‑attack complex precursor C5b‑9. By halting formation of these terminal complement effectors, the drug aims to suppress complement‑mediated inflammation, endothelial injury, and cell death that follow myocardial ischemia‑reperfusion and cardiopulmonary bypass.
What the Research Shows
Preclinical animal models demonstrated that pexelizumab reduced myocardial injury after ischemia‑reperfusion. Early phase II studies reported safety and pharmacodynamic activity in patients undergoing cardiopulmonary bypass and in acute MI. Subsequent phase III trials evaluated the drug in CABG surgery and in ST‑segment‑elevation MI treated with reperfusion. A systematic review and meta‑analysis of seven randomized trials (15,196 participants) found no overall benefit on composite major adverse events, death, MI, stroke, or heart failure in the MI cohort, but a 26 % relative reduction in mortality among CABG patients. Development was later discontinued, and the compound is listed as withdrawn.
Reported Benefits
Evidence from the meta‑analysis suggests a possible mortality benefit in patients undergoing CABG surgery, with an odds ratio of 0.74 for death. Animal studies also indicated reduced myocardial enzyme release and tissue damage when complement activation was blocked. These findings support the theoretical advantage of terminal complement inhibition in limiting reperfusion injury during cardiac surgery.
Limitations of the Evidence
Large randomized trials did not demonstrate improvement in major adverse cardiac events or mortality in acute MI patients, and the overall composite outcome was neutral. The mortality benefit observed in CABG was modest and derived from a subgroup analysis. Development has been halted, leaving the drug without regulatory approval and limiting long‑term safety and efficacy data. Results are therefore confined to specific surgical settings and may not generalise to broader cardiovascular populations.
Safety Considerations
Published abstracts provide limited detail on adverse events; no specific safety signals were highlighted in the reported trials. As a complement inhibitor, theoretical concerns include increased susceptibility to infections, particularly encapsulated bacteria, but such risks were not quantified in the available literature. Consequently, the safety profile of pexelizumab remains incompletely characterised in humans.
How It Is Administered
Pexelizumab was administered intravenously, typically as an initial bolus followed by a short‑term infusion during the peri‑operative or reperfusion period. Formulations were designed for sterile infusion in a clinical setting.
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
- Journal ArticleModeratePatel MR, Granger CB2005-01-01T00:00:00.000000Z
- Journal ArticleModerateKaplan M2002-01-01T00:00:00.000000Z
- Journal ArticleModerateLevy JH, Tanaka KA2003-01-01T00:00:00.000000Z
- Journal ArticleModeratePatel JA, Ghatak SB2008-01-01T00:00:00.000000Z
- Journal ArticleHighTesta L, et al.2008-01-01T00:00:00.000000Z
- Journal ArticleModerateWhiss PA2002-01-01T00:00:00.000000Z
Frequently Asked Questions
What type of drug is pexelizumab?
Pexelizumab is a recombinant humanized single‑chain antibody fragment (scFv) that selectively binds complement component C5, blocking its activation and downstream inflammatory pathways.
Has pexelizumab been approved for clinical use?
No. Although it progressed to phase III trials for cardiac surgery and acute myocardial infarction, the program was discontinued and the compound is listed as withdrawn, with no regulatory approval.
In which clinical situation did pexelizumab show a possible benefit?
A meta‑analysis of randomized trials reported a 26 % relative reduction in mortality among patients undergoing coronary artery bypass graft surgery when pexelizumab was added to standard care.
Are there known safety concerns with pexelizumab?
The published trial reports did not detail specific adverse events. However, because it inhibits complement, theoretical risks such as increased infection susceptibility exist, though these have not been quantified in the available studies.
How was pexelizumab given to patients in the studies?
The drug was delivered intravenously, usually as a bolus followed by a brief infusion administered around the time of surgery or reperfusion therapy.
What is Pexelizumab?
Pexelizumab is a recombinant humanized single‑chain antibody fragment (scFv) that blocks complement component C5. Developed by Alexion for cardiovascular use, it was investigated as an adjunct in coronary artery bypass graft (CABG) surgery and acute myocardial infarction (MI) to reduce reperfusion‑related injury. The compound never achieved regulatory approval and has been withdrawn from development, remaining in the research domain.
What is Pexelizumab used for?
Pexelizumab is educationally associated with: Reduction of myocardial injury post-CABG, Complement inhibition during cardiopulmonary bypass, Reduction of infarct size in STEMI/AMI. Educational only — not medical advice.
How is Pexelizumab administered?
Recorded routes of administration: Intravenous.
What are the potential side effects of Pexelizumab?
Reported adverse effects include: Increased susceptibility to encapsulated bacterial infections, Headache, Infusion-related reactions. This list is not exhaustive — consult a qualified clinician.
Who should avoid Pexelizumab?
Recorded contraindications: Unvaccinated patients (meningococcal), Active Neisseria meningitidis infection. Consult a qualified clinician before use.