Monoclonal Antibodies: Edrecolomab and Abciximab

Kowsalya

CST Pharmacist, Kauvery Hospital, Trichy

In the therapeutic monoclonal antibodies series, lets us see the overview of the third and fourth MAbs, which received EU approval in the – same year 1995.

Edrecolomab

This medication was never approved by the FDA, but was the first monoclonal antibody approved for a cancer indication, in Germany (1995). Edrecolomab is a murine IgG2A monoclonal antibody that targets the human tumor-associated antigen Ep-CAM (17-1A). In a study of 189 patients with resected stage III colorectal cancer, treatment with edrecolomab resulted in a 32% increase in overall survival compared with no treatment (P<0.01).

Mechanism of action

From the NCI Drug Dictionary: It is a murine monoclonal IgG2a antibody to tumor-associated epithelial cell adhesion molecule (EpCAM, or 17-1A) antigen. Edrecolomab attaches to EpCAM, a human cell surface glycoprotein that is found on normal epithelial cells and some tumor cells, such as those of colon and breast carcinomas. Upon binding, this agent recruits the body’s immune effector cells, which may exhibit antitumor cytotoxicity.

Dosage

Edrecolomab is administered, as single agent, by intravenous infusion at 500 mg after surgery, followed by 4 doses of 100 mg given every 4 weeks.

Current studies of Edrcolomab

Edrecolomab is also currently being tested in large multicenter adjuvant phase III studies in stage II/III rectal cancer and stage II colon cancer. Edrecolomab is currently the only antibody to be used in the adjuvant setting.

Uses

Edrecolomab was well tolerated when used as monotherapy and added little to chemotherapy-related side effects when used in combination. Sequential treatment of patients with metastatic breast cancer with edrecolomab after adjuvant chemotherapy reduced levels of disseminated tumor cells in the bone marrow and eliminated Ep-CAM-positive micrometastases (Kirchner et al., 2002).

Withdrawal of drug

Edrecolomab was withdrawn from the market after a study of its use in adjuvant treatment of patients with resected stage III colon cancer showed that disease-free survival was significantly lower with edrecolomab monotherapy than with chemotherapy and that there were hypersensitivity reactions in 452 patients (25%), causing treatment withdrawal in 71 (4%) [120C]. In a follow-up study of the natural history of patients with stage II colon cancer treated with edrecolomab there was no evidence of efficacy and grade 3 adverse reactions occurred in 242 of 823 participants (29%) who reporting adverse events; 48 (5.8%) had grade 4 reactions [121C]. The most prevalent adverse event was diarrhea, 4.1% of patients experiencing a maximum of grade 3 or 4.

References

Adkins JC, et al. Edrecolomab (monoclonal antibody 17-1a). Drugs 56: 619-626, 1998. 120 Schwartzberg LS: Clinical experience with edrecolomab: a monoclonal antibody therapy for colorectal carcinoma. Crit Rev Oncol Hematol. 2001;40:17-24.

Khazaeli MB, et al. Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. II. Pharmacokinetics and immune response. J Natl Cancer Inst. 1988;80:937-942.

ABCIXIMAB

Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention.

Background

Abciximab is a Fab fragment of the chimeric human-murine monoclonal antibody 7E3. Abciximab binds to the glycoprotein (GP) IIb/IIIa receptor of human platelets and inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules. It also binds to vitronectin (αvβ3) receptor found on platelets and vessel wall endothelial and smooth muscle cells.

Mechanism of action

Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion.

Uses

Abciximab is used to lessen the chance of heart attack in people who need percutaneous coronary intervention (PCI), a procedure to open blocked arteries of the heart.

A heart attack may occur when a blood vessel in the heart is blocked by a blood clot. Blood clots can sometimes form during PCI. Abciximab reduces the chance that a harmful clot will form by preventing certain cells in the blood from clumping together. Abciximab is used with aspirin and heparin, which are other medicines used to keep your blood from clotting.

Current Studies

Abciximab is currently a prescription-only medication only indicated for intravenous (IV) use. Further studies and randomized controlled trials (RCTs) are necessary to provide more interventions for this drug. Studies have shown abciximab to be effective in the prevention of ischemic cardiac complications in patients undergoing percutaneous coronary intervention and prevention of ischemic cardiac complications in patients with unstable angina (UA)/non-ST-elevation myocardial infarction (NSTMI) unresponsive to conventional therapy when scheduling PCI within 24 hours. Abciximab has only had research performed in conjunction with aspirin and heparin.

References

Bedjaoui A, et al. Intracoronary or intravenous abciximab after aspiration thrombectomy in patients with STEMI undergoing primary percutaneous coronary intervention. Cardiovasc J Afr. 2019;30(1):45-51.

Amoroso G, et al. Eptifibatide and abciximab exhibit equivalent antiplatelet efficacy in an experimental model of stenting in both healthy volunteers and patients with coronary artery disease. J Cardiovasc Pharmacol. 2001;38(4):633-41.

Weber AA, et al. Low incidence of paradoxical platelet activation by glycoprotein IIb/IIIa inhibitors. Thromb Res. 2002;106(1):25-9.

Hall PR, et al. Characterization and NMR solution structure of a novel cyclic pentapeptide inhibitor of pathogenic hantaviruses. Chem Biol Drug Des. 2007;69(3):180-90.

Monoclonal Antibodies: Edrecolomab and Abciximab