Tivozanib, is a potent, selective, long half-life inhibitor of all three vascular endothelial growth factor (VEGF) receptors that is designed to optimize VEGF blockade while minimizing off-target toxicities.
On February 14, 2014, AVEO and Astellas announced their decision to terminate their collaboration for the development and commercialization of tivozanib. Costs for on-going tivozanib-related expenses will be shared by the parties. Based on the terms of the agreement, all rights for tivozanib will revert to AVEO in August 2014, six months after Astellas notified AVEO of its intention to terminate the agreement. AVEO plans to explore potential partnership opportunities for the further clinical development of tivozanib.
VEGF in Solid Tumors
The vascular endothelial growth factor (VEGF) pathway plays a significant role in angiogenesis, which is critical in cancer. Angiogenesis, the formation of new blood vessels, is essential for endothelial cell proliferation, migration and survival. There are five known VEGF ligands (A, B, C, D, PLGF) and three VEGF receptors (1, 2 and 3). Each ligand exhibits distinct but overlapping binding profiles for the three VEGF receptors.
To optimally inhibit the VEGF pathway it may be critical to effectively block all three VEGF receptors as each plays an important role in cancer angiogenesis:
- VEGF receptor 1 is critical for the modulation of endothelial cell survival and vessel morphogenesis;
- VEGF receptor 2 is thought to be the predominant receptor for endothelial cell proliferation and migration; and,
- VEGF receptor 3 promotes endothelial sprouting and vascular network formation.
Preclinical studies have demonstrated tivozanib is a potent, selective, long half-life inhibitor of all three VEGF receptors that is designed to optimize VEGF blockade while minimizing off-target toxicities.