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AVEO Pharmaceuticals' Tivozanib Demonstrates Progression-Free Survival of 14.8 Months in Subgroup of Patients with Advanced Kidney Cancer; Extended Duration of Treatment Continues to Highlight Favorable Tolerability Profile
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Additional Phase 2 Data Presented at ASCO; Phase 3 TIVO-1 Trial Underway to Evaluate Tivozanib's Efficacy and Safety Profile

CAMBRIDGE, Mass. & CHICAGO, Jun 07, 2010 (BUSINESS WIRE) --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.

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(R) (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(R). Secondary endpoints include overall survival, objective response rate, safety and quality of life. Patients who demonstrate disease progression during treatment with Nexavar(R) 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 clinicaltrials@aveopharma.com.

About Tivozanib

Tivozanib, an investigational new drug, is a highly potent and selective inhibitor of VEGF receptors 1, 2 and 3, exhibiting picomolar inhibitory activity against all three receptors. Due to its potency and specificity, AVEO believes tivozanib may enable optimal inhibition of the VEGF pathway, while minimizing side effects associated with off-target activity. Such a profile may enable tivozanib to be more readily combined with standard chemotherapy as well as other targeted therapies, potentially increasing the breadth of its clinical utility.

Following the successful completion of Phase 1 and Phase 2 clinical trials, AVEO has launched a comprehensive clinical development program in support of tivozanib. In addition to the TIVO-1 trial, AVEO is currently conducting multiple Phase 1b clinical trials of tivozanib in various combinations and dosing regimens in RCC and additional solid tumor indications, including breast cancer and colorectal cancer.

About AVEO

AVEO Pharmaceuticals (NASDAQ: AVEO) integrates a proprietary cancer biology platform with drug development and commercial expertise in its efforts to discover and develop targeted cancer therapeutics. The company's lead product, tivozanib, is an oral, triple VEGF receptor inhibitor with potential for a best-in-class profile. Tivozanib is currently being investigated in a global, randomized Phase 3 clinical trial called TIVO-1 comparing tivozanib to sorafenib in advanced kidney cancer, as well as additional clinical studies in other solid tumor types. AVEO's proprietary, integrated cancer biology platform offers the company a unique advantage in oncology drug development that both increases the probability of clinical success and provides a discovery engine for high-value targets. This approach has resulted in a promising pipeline of monoclonal antibodies against novel targets including HGF, ErbB3, RON, Notch and FGFR. For more information, please visit the company's website at www.aveopharma.com.

Any statements in this press release about our future expectations, plans and prospects, including statements about patients and physician's need to access a potent and targeted VEGF therapy, tivozanib's potential to improve quality of life and compliance for patients, tivozanib being a potential advance to a next generation of RCC therapy, the continued execution of the tivozanib clinical trial program, the proposal that hypertension could be biomarker of clinical effect among agents targeting the VEGF receptor tyrosine kinases in RCC, tivozanib's potency and tolerability as compared to existing treatments for RCC,tivozanib's potential as an important and highly differentiated new therapeutic option to treat RCC,the company's cancer biology platform increasing the probability of clinical success and providing a discovery engine for high-value targets, and other statements containing the words "believes," "anticipates," "plans," "expects," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks relating to: our ability to successfully research, develop and obtain and maintain regulatory approvals for tivozanib and our other product candidates, including our ability to obtain and maintain market authorization for tivozanib in the EU; the possibility that positive results in our Phase 2 clinical trial of tivozanib may not be predictive of the results in our Phase 3 clinical trial; our inability to obtain and maintain adequate protection for intellectual property rights relating to our product candidates and technologies; unplanned operating expenses and our ability to raise substantial additional funds to achieve our goals; general economic and industry conditions; and other factors discussed in the "Risk Factors" section of our most recent Form 10-Q filed with the Securities and Exchange Commission, and in other filings that we periodically make with the SEC. In addition, the forward-looking statements included in this press release represent our views as of the date of this press release. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.

SOURCE: AVEO Pharmaceuticals, Inc.

AVEO Pharmaceuticals, Inc.
David Johnston, Chief Financial Officer
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Sheryl Seapy, 949-608-0841