Final analysis of AVEO's tivozanib Phase 2 trial on kidney cancer patients presented at ASCO 2011

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 47^th 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.S. Worldwide it is estimated that more than 200,000 people are diagnosed and more than 100,000 people die from the disease each year. RCC accounts for 90 percent of all malignant kidney tumors. 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 toxicities^.

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."

Source: AVEO Pharmaceuticals, Inc.