Tivozanib

Tivozanib (AV-951) is an oral VEGF receptor tyrosine kinase inhibitor. It is undergoing clinical trial investigation for the treatment of renal cell carcinomas. An oral quinoline urea derivative, tivozanib suppresses angiogenesis by being selectively inhibitory against vascular endothelial growth factor. It was developed by AVEO Pharmaceuticals. It is designed to inhibit all three VEGF receptors.

Phase III results on advanced renal cell carcinoma suggest a 30% or 3 months improvement in median PFS compared to sorafenib. The Food and Drug Administration's Oncologic Drugs Advisory Committee voted in May 2013 13 to 1 against recommending approval of tivozanib for renal cell carcinoma. The committee felt the drug failed to show a favorable risk-benefit ratio and questioned the equipose of the trial design, which allowed control arm patients who used sorafenib to transition to tivozanib following progression disease but not those on the experimental arm using tivozanib to transition to sorafenib. There was an inferior overall survival rate of the experimental arm versus the control arm in this Phase III study as well. The application was formally rejected by the FDA in June 2013, saying that approval would require additional clinical studies.