AVEO Pharmaceuticals, Inc. (NASDAQ: AVEO) announced that it has initiated patient enrollment in a multi-center Phase 2 exploratory biomarker study of tivozanib, its lead product candidate designed to optimally block the VEGF pathway by inhibiting all three VEGF receptors, in patients with renal cell carcinoma (RCC).

"We continue to leverage our Human Response Platform™ in our efforts to maximize the clinical potential of our pipeline of oncology therapeutics," said Murray Robinson, Ph.D., senior vice president, translational medicine at AVEO. "AVEO is committed to advancing the science behind biomarkers and patient treatment approaches. The identification and development of relevant biomarkers is a strategic component of our drug development efforts. We expect to use biomarker data from this study to inform the future design of rational combinations in RCC, as well as in other cancers."

This multi-center, single-arm Phase 2 study is designed to evaluate biomarkers of tivozanib in approximately 100 patients with RCC who had a prior nephrectomy at 25 sites in the U.S. and Canada. A key primary objective of the study is to evaluate biomarkers in blood and archived tissue samples and their correlation with tivozanib clinical activity and/or drug-related toxicity.

About Tivozanib

Tivozanib, an investigational new drug, is designed to optimally block the VEGF pathway by inhibiting all three VEGF receptors. Each of the three receptors of the VEGF pathway play an important role in angiogenesis (the formation of new blood vessels), which is critical in cancer cell growth. Tivozanib's high level of potency across VEGF receptors 1, 2 and 3 is designed to provide the most complete blockade of the VEGF pathway. Tivozanib's high level of selectivity for VEGF receptors 1, 2 and 3 is designed to minimize off-target toxicities, and its oral, one capsule, once-daily administration may enhance convenience for patients. Tivozanib has also demonstrated the ability to be combined with both targeted therapies and chemotherapies at the full dose and schedule1-3. AVEO is leveraging its Human Response Platform™ in order to enrich outcomes and minimize development risks for tivozanib.

In a large, multi-center, randomized Phase 2 clinical trial, the subset of patients with clear cell renal cell carcinoma (RCC) who had a prior nephrectomy receiving tivozanib therapy achieved 14.8 months progression free survival (PFS), the longest PFS reported for a single-agent therapy in this population4. The safety profile of tivozanib observed in the Phase 2 trial was notable for the minimal off-target toxicities often associated with VEGF, multi-targeted therapies. There was a low incidence of diarrhea, fatigue, stomatitis and hand-foot syndrome. Hypertension and dysphonia (hoarseness of voice), which are mechanism-related side effects associated with angiogenesis inhibitors, were the most commonly reported drug-related side effects, and both were manageable and reversible4. AVEO has completed patient enrollment in TIVO-1, a global, randomized, controlled Phase 3 clinical trial evaluating the efficacy of tivozanib compared to sorafenib (Nexavar®) in this same patient population. AVEO expects to announce top-line data from TIVO-1 in mid-2011.

1. Kabbinavar FF, et al. Presented at the International Kidney Cancer Symposium; October 1-2, 2010; Chicago, IL.

2. Mayer EL, et al. Poster presented at the SABCS Annual Meeting; December 8-12, 2010; San Antonio, TX.

3. Eskens FALM, et al. Poster presented at the EORTC-NCI-AACR International Symposium on Molecular Targets and Cancer Therapeutics; November 16-19, 2010; Berlin, Germany.

4. Bhargava P, et al. Poster presented at the ASCO Annual Meeting; June 4-8, 2010; Chicago, IL. Abstract 4599. In the tivozanib Phase 2 trial, the intent to treat patient population (n=272) achieved 11.8 months median PFS.