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, which could enable more tolerable combination with other therapies.
Tivozanib is currently being evaluated in the pivotal Phase 3 TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced RCC. The TIVO-3 trial, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support a first and third line indication for tivozanib in the U.S. Tivozanib is also being evaluated in a Phase 1/2 trial in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, Opdivo® (nivolumab) in RCC, known as the TiNivo trial. Tivozanib’s distinct tolerability profile among VEGF TKIs makes it a potentially unique candidate for use with PD-1 inhibitors.
In November 2014, AVEO entered into an option agreement with Ophthotech to investigate tivozanib for the potential treatment of non-oncologic diseases of the eye. In December 2015, AVEO entered into an exclusive licensing agreement with EUSA Pharma granting European rights to tivozanib for oncology indications. The agreement also includes a number of additional territories outside North America, including South America and South Africa, and additional potential indications. In March 2016, EUSA submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for tivozanib for the first-line treatment of advanced RCC.
AVEO is interested in collaborating with potential partners who share our vision for cancer drug development and positively impacting patients’ lives. Please contact AVEO firstname.lastname@example.org to discuss partnership opportunities with AVEO’s development pipeline.
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.