|Half-life||∼9.4 days (range: 4-11 days)|
|(what is this?)|
Panitumumab is manufactured by Amgen and marketed as Vectibix. It was originally developed by Abgenix Inc.
It 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".
Panitumumab was the first monoclonal antibody to demonstrate the use of KRAS as a predictive biomarker.
In July 2009, the FDA updated the labels of two anti-EGFR monoclonal antibody drugs (panitumumab and cetuximab) indicated for the treatment of metastatic colorectal cancer to include information about KRAS mutations.
EGFR is a transmembrane protein. Panitumumab works by binding to the extracellular domain of the EGFR preventing its activation. This results in halting of the cascade of intracellular signals dependent on this receptor.
Panitumumab was developed by immunization of transgenic mice (XenoMouse) that are able to produce human immunoglobulin light and heavy chains. After immunization of these animals a specific clone of B cells that produced an antibody against EGFR was selected and immortalized in Chinese hamster ovary (CHO) cells. These cells are then used for the full scale manufacture of the 100% human antibody.
The pharmacokinetics (PK) of panitumumab shows the so-called target-mediated disposition behavior. However, the PK is approximately linear at clinical doses, and the terminal half-life for a typical male patient of 80 kg and 60 years of age with colorectal cancer is about 9.4 days.
Panitumumab vs. cetuximab
Although they both target the EGFR, panitumumab (IgG2) and cetuximab (IgG1) differ in their isotype and they might differ in their mechanism of action. Monoclonal antibodies of the IgG1 isotype may activate the complement pathway and mediate antibody-dependent cellular cytotoxicity (ADCC).
- "Illumina, Amgen to Develop CDx for Colorectal Cancer". News: Molecular Diagnostics. Gen. Eng. Biotechnol. News (paper) 34 (4). February 15, 2014. p. 32.
- U.S. Food and Drug Administration
- OncoGenetics.Org (July 2009). "FDA updates Vectibix and Erbitux labels with KRAS testing info". OncoGenetics.Org. Retrieved 2009-07-20.[dead link]
- Plunkett, Jack W. (September 30, 2005). Plunkett's Biotech & Genetics Industry Almanac 2006. Plunkett Research, Ltd. ISBN 1-59392-033-4.
- Ma, P (2009). "Population Pharmacokinetic Analysis of Panitumumab in Patients With Advanced Solid Tumors". J Clin Pharmcol 49: 1142–1156. doi:10.1177/0091270009344989.
- HealthValue: IgG1 & IgG2
- Amado, RG; Wolf, M.; Peeters, M.; Van Cutsem, E.; Siena, S.; Freeman, D. J.; Juan, T.; Sikorski, R. et al. (2008). "Wild-Type KRAS is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer". J Clin Onco 26 (10): 1626–1634. doi:10.1200/JCO.2007.14.7116.
- Van Cutsem, E; Peeters, M.; Siena, S.; Humblet, Y.; Hendlisz, A.; Neyns, B.; Canon, J.-L.; Van Laethem, J.-L. et al. (2007). "Open-Label Phase III Trial of Panitumumab Plus Best Supportive Care Compared With Best Supportive Care Alone in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer". J Clin Onco 25 (13): 1658–1664. doi:10.1200/JCO.2006.08.1620.