AVEO Pharmaceuticals presents tivozanib’s Phase 2 trial data at ASCO meeting

AVEO Pharmaceuticals, Inc. (NASDAQ: AVEO), a biopharmaceutical company focused on discovering, developing and commercializing cancer therapeutics, today announced data from a subgroup analysis of a Phase 2 randomized discontinuation trial showing that the median progression-free survival (PFS) achieved by patients with advanced clear cell renal cell carcinoma (RCC) who had undergone a prior nephrectomy was 14.8 months. Additionally, PFS was similar between those patients who were treatment naïve, and those who had received prior therapy with cytokines and/or chemotherapy. These data are being presented today at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO), abstract number 4599.

“In order to more effectively treat advanced kidney cancer, patients and physicians need access to potent and targeted VEGF pathway inhibitors”

Off-target toxicities commonly associated with other targeted therapies, such as mucositis, fatigue and hand-foot syndrome, were notably low during treatment with tivozanib.

"In order to more effectively treat advanced kidney cancer, patients and physicians need access to potent and targeted VEGF pathway inhibitors," stated Michael B. Atkins, M.D., professor of medicine, Beth Israel Deaconess Medical Center and Harvard Medical School. "The efficacy observed with tivozanib in this Phase 2 analysis compares favorably to historical data from trials testing currently approved VEGF receptor inhibitors in patients with advanced kidney cancer, and the tolerability profile underscores the potential for improved quality of life and compliance. I believe these tivozanib data signal a potential advance to a next generation of RCC therapy."

The Phase 2 placebo-controlled, randomized discontinuation trial assessed the efficacy and safety of once-daily, oral tivozanib in 272 patients with locally advanced or metastatic RCC. Approximately 83% of patients enrolled had clear cell RCC, and approximately 73% had undergone a prior nephrectomy. Patients received treatment once-daily for three weeks followed by one week off (one cycle over four weeks). Efficacy - objective response rate (ORR) and PFS - was analyzed in all treated patients as well as in patients who attained 25% regression during the first 16 weeks, and those who had a less than 25% change from baseline and were randomized to tivozanib or placebo.

Highlights from the analyses as assessed by independent radiological review include:

• Median PFS among all 272 patients was 11.8 months;
• Median PFS of patients with clear cell RCC who had undergone a prior nephrectomy was 14.8 months;
• PFS was significantly higher among patients with clear cell RCC (12.5 months) vs. non clear cell RCC (6.7 months) and among those with prior nephrectomy (14.1 months) vs. no prior nephrectomy (8.2 months), and;
• Within the group of 176 patients with clear cell histology and prior nephrectomy, PFS was similar between those patients who were "treatment naïve" (14.3 months), and those who had received prior therapy with cytokines and/or chemotherapy (15.8 months).

"We believe these data underscoring the efficacy and safety of our lead candidate tivozanib in patients with clear cell RCC who had undergone a prior nephrectomy are important, as this is the same patient population that is currently being studied in TIVO-1, our global Phase 3 clinical trial evaluating the efficacy of tivozanib compared to sorafenib," stated Tuan Ha-Ngoc, president and chief executive officer of AVEO. "We look forward to continued execution of our clinical development program across a wide range of tumor types both as a single agent and in combination with other anti-cancer therapies."

The safety profile of tivozanib observed in the Phase 2 trial was notable for the minimal off-target toxicities often associated with other VEGF, multi-targeted therapies. Hypertension (50%) and dysphonia (hoarseness of voice, 21.7%) were the most commonly reported treatment-related adverse events, mostly grades 1 and 2. There was a low incidence of diarrhea (12.1%), fatigue (8.1%), stomatitis (4.4%) and hand-foot syndrome (3.7%).

Additional analyses from the Phase 2 study were presented in March at the 2010 Genitourinary Cancers Symposium, and showed that the median PFS was 21.4 months for a subset of patients with clear cell RCC who had undergone nephrectomy and had a diastolic blood pressure greater than 90 mm Hg. Hypertension is believed to be directly related to the mechanisms of VEGF pathway inhibition and development of hypertension was associated with improved clinical outcomes among patients treated with tivozanib.

AVEO has initiated patient enrollment in TIVO-1, a global Phase 3 clinical trial of tivozanib, which is expected to enroll approximately 500 patients with advanced RCC who have not received prior VEGF-targeted therapy. TIVO-1 is evaluating the efficacy of tivozanib compared to Nexavar^® (sorafenib), an FDA and EMA approved therapy for advanced RCC. TIVO-1 is the first-ever Phase 3 study in RCC designed to evaluate superiority in a head-to-head comparison against a widely prescribed anti-angiogenesis therapy in first-line RCC. The primary endpoint of the trial is to compare the PFS of tivozanib vs. Nexavar^®. Secondary endpoints include overall survival, objective response rate, safety and quality of life. Patients who demonstrate disease progression during treatment with Nexavar^® will have the opportunity to be treated with tivozanib by participating in a separate long-term treatment protocol.

This trial is currently enrolling patients and is being led by Robert Motzer, M.D. from the Memorial Sloan-Kettering Cancer Center. Individuals with RCC of clear cell histology that have had a prior nephrectomy and that have not received prior VEGF-targeted therapy are eligible for TIVO-1. If you would like more information on the TIVO-1 trial, please contact AVEO Pharmaceuticals' clinical operations department at [email protected].