CAMBRIDGE, Mass. and TOKYO, Japan, October 1, 2012 - AVEO Oncology (NASDAQ: AVEO) and Astellas Pharma Inc. (TSE: 4503) today announced new data from the Phase 3 TIVO-1 trial (TIvozanib Versus sOrafenib in 1st line advanced RCC) demonstrating the safety and tolerability profile of tivozanib versus sorafenib in the first line setting for patients with metastatic renal cell carcinoma (RCC). Results presented at the ESMO 2012 Congress (European Society for Medical Oncology) in Vienna, Austria show that patients treated with tivozanib experienced fewer Grade 3 and off-target adverse events (AEs), stayed on treatment longer, and required fewer dose reductions and interruptions compared with those treated with sorafenib.1 Also presented were the first tivozanib biomarker data in RCC, and the design of the TAURUS (TivozAnib Use veRsUs Sunitinib in advanced renal cell carcinoma) patient preference study, in which the first patient has now been enrolled. AVEO recently submitted a New Drug Application to the U.S. Food and Drug Administration seeking approval for tivozanib.

“Minimizing toxicities associated with anti-VEGF therapy is a vital consideration in RCC. Adverse events have been shown to contribute to dose reductions, interruptions and discontinuations of anti-VEGF therapy,” said Timothy Eisen, Ph.D., FRCP, study investigator, Cambridge University Health Partners. “The data from TIVO-1 show that treatment with tivozanib led to fewer side effects and lower rates of dose modifications than with sorafenib. This suggests that it is easier to maintain full dose therapy with tivozanib.”

The TIVO-1 global, randomized Phase 3 clinical trial compared the safety and tolerability of tivozanib and sorafenib in 517 patients with advanced RCC. Results of the trial were presented at the ASCO Annual Meeting earlier this year and showed that tivozanib demonstrated a statistically significant improvement in progression-free survival (PFS) compared with sorafenib in the overall patient population (median PFS 11.9 months versus 9.1 months; p=0.042, HR=0.797). Further, in a pre-specified subset of RCC patients who were treatment-naïve, tivozanib demonstrated a statistically significant improvement in PFS with a median of 12.7 months compared with 9.1 months for sorafenib (p=0.037; HR=0.75), making tivozanib the first treatment to demonstrate a median PFS of greater than one year in this patient population.2 Tivozanib is an investigational drug being evaluated for first-line treatment of advanced RCC.

Title: Detailed Comparison of the Safety of Tivozanib Versus Sorafenib in Patients with Advanced/Metastatic Renal Cell Carcinoma (mRCC) from a Phase 3 Trial 
Date/Poster/Location: Oct. 1, 1:00-2:00pm CET / 7:00-8:00am ET; Poster #795PD; Hall F2

Investigators evaluated drug-related AEs versus sorafenib with the goal of better understanding the tivozanib safety profile. The results of the safety analysis showed:

• Investigator-reported adverse events for tivozanib showed lower rates of dose reductions, interruptions, and discontinuations compared to sorafenib: dose reductions (11.6% vs. 42.8%, p<0.001), interruptions (17.8% vs. 35.4%, p<0.001), and discontinuations (4.2% vs. 5.4%)1 
• Drug-related AEs occurred in fewer patients on tivozanib than patients on sorafenib (67.6% vs. 83.3%)1
• Fewer patients in the tivozanib group had ≥Grade 3 drug-related AEs than patients in the sorafenib group (36.3% vs. 51.0%, respectively).1 ≥Grade 3 hypertension, an established on-target effect of angiogenesis inhibitors, was more common in the tivozanib group (23.6% vs. 15.2%), and ≥Grade 3 hand-foot syndrome (1.9% vs. 16.7%), diarrhea (1.9% vs. 5.8%) and lipase elevation (0.8% vs. 5.8%) were more common in the sorafenib group.1

“Our tivozanib development program in RCC is comprehensive and ongoing. With positive safety and efficacy data from TIVO-1 in-hand, we continue to explore the role of biomarkers and patient preference with the ultimate goal of helping clinicians optimize RCC treatment,” said William Slichenmyer, M.D., Sc.M., chief medical officer at AVEO. “Additional analyses from our ongoing biomarker program will be presented at future congresses and our TAURUS patient preference study vs. Sutent® (sunitinib) is now underway.”

In addition to detailed safety results, pharmacokinetic/pharmacodynamic data from TIVO-1 were also presented.3

Title: Tivozanib Pharmacokinetic/Pharmacodynamic Analysis of Blood Pressure and Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2) in Patients with Advanced Renal Cell Carcinoma
Date/Poster/Location: Oct. 1, 1:00-2:00pm CET / 7:00-8:00am ET; Poster #796PD; Hall F2

Analyses were conducted using pooled data from patients in AVEO’s randomized placebo-controlled Phase 2 study of tivozanib in RCC and from the TIVO-1 study to explore the relationship between tivozanib exposure, blood pressure and sVEGFR2.3

Patients in the analysis showed a median increase in diastolic blood pressure of 5mm Hg compared with baseline, and also experienced a decrease in sVEGFR2 corresponding to tivozanib exposure.3 Hypertension and sVEGFR are known to be on-target biomarkers of activity and clinical outcome.4,5,6

“One of our goals in becoming a global Category Leader in oncology is to develop precision medicines that revolutionize the methods used to treat patients with cancer,” said Stephen Eck, M.D., Ph.D., Vice President of Medical Oncology, Astellas Pharma Global Development. “We believe the data showing the combination of tivozanib’s statistically significant PFS and its tolerability profile represents a potentially important advancement in the treatment of this disease.”

Title: Patient Preference for Tivozanib Hydrochloride or Sunitinib in the Treatment of Metastatic Renal Cell Carcinoma (mRCC): TAURUS study 
Date/Poster/Location: Sep. 29, 1:00-2:00pm CET / 7:00-8:00am ET; Poster #892TiP; Hall XL

A review of the clinical study design of TAURUS, a randomized (1:1), double-blind, crossover controlled, multi-center Phase 2 study comparing tivozanib versus sunitinib in approximately 160 patients with advanced RCC who have received no prior systemic therapy was presented at the meeting. The primary objective of the study is to compare patient preference for tivozanib or sunitinib.

The first patient has been enrolled in TAURUS, and the study will continue to enroll patients at sites throughout the United States and Western Europe.