June 2, 2011

Final Analysis from AVEO Pharmaceuticals’ Phase 2 Trial of Tivozanib in Patients with Advanced Renal Cell Carcinoma Presented at ASCO

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Median PFS Was 11.7 Months among All Treated Patients and 14.8 Months among Those with Clear Cell RCC Who Had Undergone Nephrectomy; Phase 1 Combination Data in RCC and Breast Cancer Also Presented

CAMBRIDGE, Mass. & CHICAGO, Jun 02, 2011 (BUSINESS WIRE) — AVEO Pharmaceuticals, Inc. (NASDAQ:AVEO), today announced data from the final analysis of its Phase 2 randomized discontinuation trial evaluating tivozanib, its lead product candidate designed to optimally block the VEGF pathway by inhibiting all three VEGF receptors, in patients with advanced renal cell carcinoma (RCC). Data showed that the median progression-free survival (PFS) achieved among all patients (both clear cell and non-clear histologies) treated with tivozanib was 11.7 months and, as previously presented, 14.8 months among those with clear cell RCC who had undergone nephrectomy, which is the same patient population being evaluated in AVEO’s ongoing Phase 3 trial comparing tivozanib to sorafenib (Nexavar®), called TIVO-1. Additionally, Phase 1 data evaluating tivozanib in combination with the mTOR inhibitor temsirolimus (Torisel®) in patients with RCC demonstrated tolerability and tumor shrinkage. These data are being presented in two poster discussion sessions at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO), abstracts number 4550 and 4549, respectively.

Advanced RCC, or kidney cancer, is the eighth most commonly diagnosed cancer in men and women in the U.S1. Worldwide it is estimated that more than 200,000 people are diagnosed and more than 100,000 people die from the disease each year2. RCC accounts for 90 percent of all malignant kidney tumors3. Despite advances in RCC therapies, significant unmet need persists. Currently available therapies provide patients less than one year of survival without disease progression and are associated with significant toxicities4-7.

Off-target toxicities commonly associated with other targeted RCC therapies, such as mucositis, fatigue and hand-foot syndrome, were notably low during treatment with tivozanib in the Phase 2 monotherapy study. In the Phase 1 combination study, the combination of tivozanib and temsirolimus was well tolerated, with the incidence of adverse events similar to the safety profiles of these agents administered as monotherapy in RCC patients.

“In order to most effectively treat advanced kidney cancer, patients and physicians may benefit from access to potent and targeted VEGF pathway inhibitors that are safe on their own as well as in combination with other anti-cancer therapies,” stated Fairooz Kabbinavar, M.D., professor of medicine and urologic oncology, Henry Alvin and Carrie L. Meinhardt chair in Kidney Cancer Research, director, Hematology-Oncology Fellowship Program, medical director, Thoracic Oncology and Kidney Cancer Programs, David Geffen School of Medicine, University of California, Los Angeles, and co-investigator of the Phase 1b study. “The efficacy and anti-tumor activity observed in these studies indicate significant tivozanib potency, while the safety and tolerability data suggest a notable advance over currently available targeted therapies associated with dose-limiting toxicities. I am encouraged by these data and the potential for tivozanib to play a critical role in the treatment of patients battling advanced kidney cancer.”

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 and no prior VEGF-targeted therapy. 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 final analysis as assessed by independent radiological review include:

  • Objective response rate (ORR) as assessed by independent radiological review in the overall study population was 24% and 30% among patients with clear cell RCC who had undergone nephrectomy;
  • Median PFS was 11.7 months among all treated patients and 14.8 months among those with clear cell RCC who had undergone nephrectomy;
  • In the overall study population, 84% of patients experienced tumor shrinkage during tivozanib therapy;
  • Percentage of patients progression-free at 12 weeks following randomization was significantly higher among patients treated with tivozanib (49%) versus placebo (21%); and
  • Tivozanib therapy demonstrated a positive safety profile with low incidences of off-target toxicities:
    • Low incidence of diarrhea (12%), asthenia (10%), fatigue (8%), stomatitis (4%) and hand-foot syndrome (4%); and
    • Hypertension (45%) and dysphonia (hoarseness of voice, 22%), which are mechanism-related side effects associated with angiogenesis inhibitors, were the most commonly reported treatment-related adverse events, mostly grades 1 and 2.

Results from a Phase 1 combinability study assessing once-daily, oral tivozanib (three weeks on, one week off) and temsirolimus (intravenously once weekly) in 27 patients with RCC will also be presented at ASCO. Among 22 patients evaluable for efficacy, 86 percent demonstrated tumor reduction; of those, 23 percent achieved a partial response and 68 percent maintained stable disease. The maximum tolerated dose for the combination was tivozanib 1.5 mg/day plus temsirolimus 25 mg/week. There were no dose limiting toxicities observed in the study.

“We believe these Phase 1 and Phase 2 data further validate the potential efficacy and safety of our lead candidate tivozanib in patients with advanced RCC and signal significant promise for the utility of tivozanib as both a single agent and in combination with other anti-cancer therapies,” stated William J. Slichenmyer, M.D., Sc.M., chief medical officer of AVEO. “We are continuing to execute our tivozanib clinical development program, in collaboration with our colleagues at Astellas, across a broad range of solid tumor types and look forward to obtaining results from our pivotal Phase 3 trial, TIVO-1, evaluating tivozanib compared to sorafenib in RCC in the fourth quarter of this year at the earliest.”

Tivozanib and Paclitaxel Combination Data in Breast Cancer

Also being presented at ASCO are previously reported results from a Phase 1 study evaluating tivozanib in combination with paclitaxel (Taxol®), a standard chemotherapy regimen, in patients with metastatic breast cancer. The Phase 1b open-label, dose-escalation study assessed once-daily, oral tivozanib (sequential cohorts of 0.5, 1.0 and 1.5 mg/day for three weeks on, one week off) and paclitaxel (once-weekly intravenously for three weeks on, one week off) in 18 patients with metastatic breast cancer, all of whom had prior taxane therapy and most of whom had prior bevacizumab therapy. Key findings demonstrated that ORR among the 13 patients evaluable for efficacy was 38 percent with a median response duration of 6.7 months, and that stable disease was achieved by 54 percent of patients with a median duration of 8.5 months. Confirmed partial responses were observed in five of the 18 patients, as evaluated by standard Response Evaluation Criteria in Solid Tumors (RECIST). The combination of tivozanib and weekly paclitaxel was tolerable at all dose levels, and the side-effect profile was manageable; the most common adverse events included fatigue, alopecia, diarrhea, nausea and peripheral sensory neuropathy.

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 plays 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 schedule. AVEO is leveraging its Human Response Platform(TM) in order to enrich outcomes and minimize development risks for tivozanib.

About AVEO

AVEO Pharmaceuticals (NASDAQ:AVEO) is a cancer therapeutics company committed to discovering, developing and commercializing targeted therapies to impact patients’ lives. The company’s lead product candidate, tivozanib, is currently being investigated in a global, randomized Phase 3 clinical trial called TIVO-1 comparing tivozanib to sorafenib in patients with advanced renal cell carcinoma, as well as additional clinical studies in other solid tumor types. AVEO’s second most advanced product candidate, ficlatuzumab (AV-299), is a potent, functional anti-HGF/c-MET pathway antibody that is currently in Phase 2 clinical development. AVEO’s proprietary Human Response Platform(TM) is designed to offer the company a unique advantage in cancer drug development and has provided a discovery engine for multiple therapeutic 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.

Cautionary Note Regarding Forward-Looking Statements

Any statements in this press release about our future expectations, plans and prospects, including statements about: the potential efficacy and safety of tivozanib; tivozanib’s therapeutic potential, as both a single agent and in combination with other anti-cancer therapies; the expected timing of results from TIVO-1; the potential of our cancer biology platform to offer a unique advantage in oncology drug development; and other statements containing the words “believes,” “anticipates,” “plans,” “expects,” “potential,” “will,” 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; the possibility that favorable preclinical trial results may not be predictive of the results in future preclinical and clinical trials; our inability to obtain and maintain adequate protection for intellectual property rights relating to our product candidates and technologies; unplanned operating expenses; our inability to raise substantial additional funds to achieve our goals, including with respect to the further development of tivozanib; competition; 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.

1. www.cancer.org/cancer/kidneycancer; http://seer.cancer.gov/statfacts/html/kidrp.html

2. Cancer Research UK http://info.cancerresearchuk.org/cancerstats/world/commoncancers/; GLOBOCAN http://globocan.iarc.fr/factsheets/populations/factsheet.asp?uno=900#BOTH

3. Decision Resources December 2010 All Rights Reserved

4. Escudier, B., et al. NEJM 2007 – Nexavar

5. Motzer, R. J., et al. JCO 2009 – Sutent

6. Hutson, T., et al. JCO 2009 – pazopanib Phase 2

7. Rini, B., et al. JCO. 2009;27(27):4462-4468 – axitinib Phase 2

SOURCE: AVEO Pharmaceuticals, Inc.

AVEO Pharmaceuticals, Inc.
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