Panitumumab Overview

Introduction of Panitumumab

Panitumumab, formerly ABX-EGF, is a fully human monoclonal antibody (mAb) specific to the epidermal growth factor receptor (also known as EGF receptor, EGFR, ErbB-1 and HER1 in humans). Panitumumab was originally developed by Abgenix using Abgenix's XenoMouse platform technology, in which engineered mice were utilized to produce human antibodies. This methodology is based on inactivating the mouse immunoglobulin genes that are replaced by a megabase gene containing the human heavy and κ chains. The result is the generation of fully human antibodies that do not contain murine portions of the IgG molecule as chimeric antibodies do. This property avoids the formation of human antimouse antibodies, which may result in more frequent hypersensitivity reactions and shorter half-life.

Abgenix partnered with Immunex to develop the antibody in 2013. Amgen acquired Immunex and Abgenix successively. Amgen and Takeda have an agreement under which Takeda will develop and commercialize panitumumab in Japan. Panitumumab is licensed to Dr. Reddy's Laboratories in India and GlaxoSmithKline in the UK. Panitumumab was approved by the U.S. Food and Drug Administration (FDA) for the first time in September 2006, for the treatment of EGFR-expressing metastatic colorectal cancer with disease progression despite prior treatment. Panitumumab was approved by the European Medicines Agency (EMEA) in 2007, and by Health Canada in 2008 for the treatment of refractory EGFR-expressing metastatic colorectal cancer in patients with non-mutated (wild-type) KRAS. In July 2009, the FDA updated the labels of two anti-EGFR mAb drugs (panitumumab and cetuximab) indicated for the treatment of metastatic colorectal cancer to include information about KRAS mutations. In addition, it is also approved as a first-line agent in combination with FOLFOX.

Mechanism of Action of Panitumumab

EGFR, a tyrosine kinase transmembrane receptor belonging to the ErbB family, plays a crucial role in cell proliferation, survival, and differentiation in many malignancies due to EGFR dysregulation. Many ligands, in addition to epidermal growth factor (EGF), are involved in EGFR activation, including transforming growth factor alpha, amphiregulin, betacellulin, epigen, epiregulin, and heparin-binding EGF. These various ligands are capable of binding to the extracellular ligand-binding domain to activate downstream mechanisms for tumor development and proliferation. EGFR activation leads to several signaling pathways, including RAS/RAF/MEK/ERK, PI3CK/AKT/mTOR, Src family kinases, STATs, and PLCγ-PKC, thus leading to cell survival through tumor growth, angiogenesis, tumor invasion, and migration. EGFR is overexpressed in certain human cancers, including colon and rectal cancer. Panitumumab binds specifically to the extracellular domain of EGFR on both normal and tumor cells, competitively inhibiting the binding of other ligands to EGFR and thus preventing receptor phosphorylation and subsequent activation of downstream signaling cascade. This results in inhibition of cell growth, induction of apoptosis, decreased proinflammatory cytokine and vascular growth factor production, and EGFR downregulation through receptor internalization.

Fig.1 Mechanism of action of Panitumumab

Table 1. Clinical Projects of Panitumumab*

Table 2. Approved Drugs of Panitumumab**

INN (trade name)	Therapeutic area	Dose	Strength	Route	Company	Marketing start	Market
Vectibix	Wild-Type RAS Metastatic Colorectal Cancer	Concentrate for solution	20 mg / mL	Intravenous infusion	Amgen	September 27, 2006
Vectibix	Colorectal Neoplasms	Concentrate for solution	20 mg / mL	Intravenous infusion	Amgen Europe B.V.	December 3, 2007
Vectibix	Wild-Type RAS Metastatic Colorectal Cancer	Concentrate for solution	20 mg / mL	Intravenous infusion	Amgen Canada Inc	May 27, 2008
Vectibix	Wild-Type RAS Metastatic Colorectal Cancer	Concentrate for solution	20 mg / mL	Intravenous infusion	Amgen Australia Pty Ltd	May 14, 2008
Vectibix	Wild-Type RAS Metastatic Colorectal Cancer	Concentrate for solution	20 mg / mL	Intravenous infusion	Takeda Pharmaceutical Co., Ltd.	April 16, 2010

What We Provide

Therapeutic Antibody

Panitumumab

We provide high-quality Panitumumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=Panitumumab

**Information presented in the table were collected from the following website:
http://search.tga.gov.au/s/search.html?collection=tga-artg&profile=record&meta_i=128270
http://www.pmda.go.jp/PmdaSearch/iyakuDetail/GeneralList/4291417A1
https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=79412
https://www.ema.europa.eu/en/medicines/human/EPAR/vectibix
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125147

For research use only. Not intended for any clinical use.