AVEO Pharmaceuticals, Inc. (NASDAQ: AVEO), a biopharmaceutical company focused on discovering, developing and commercializing cancer therapeutics, today announced that it has achieved its enrollment target for TIVO-1, its global Phase 3 clinical trial for its oral, triple VEGF receptor inhibitor, tivozanib, in patients with advanced renal cell carcinoma (RCC). In February of this year, AVEO initiated enrollment in TIVO-1, and has successfully reached the target enrollment of 500 patients.
“The enrollment in this trial underscores the need for improved treatment options for this difficult-to-treat cancer,” stated Robert Motzer, M.D., attending physician at Memorial Sloan-Kettering Cancer Center and global lead TIVO-1 study investigator. “The results from this trial have the potential to provide the medical community with an understanding of tivozanib’s efficacy and tolerability in patients with advanced renal cell carcinoma.”
TIVO-1 is a global, randomized (1:1), controlled trial evaluating tivozanib compared to sorafenib. The primary endpoint of the trial is to compare the progression-free survival (PFS) of tivozanib vs. sorafenib. Secondary endpoints include overall survival, objective response rate, duration of response and quality of life. Patients with RCC of clear cell histology that have had a prior nephrectomy and that have not received prior VEGF-targeted therapy are eligible for this trial. Prior to entering the trial, independent, central review of the CT scans was required for all patients to ensure patients met the eligibility criteria regarding measureable disease. During treatment, scans are being obtained every eight weeks, and, again, are centrally reviewed by blinded independent reviewers. Patients who demonstrate disease progression during treatment with sorafenib will have the opportunity to be treated with tivozanib by participating in a separate long-term treatment protocol.
“We are very pleased to see TIVO-1 reach our enrollment target six months ahead of schedule, and I want to thank our investigators for their enthusiastic support for and tremendous commitment to the development of tivozanib,” said Tuan Ha-Ngoc, president and chief executive officer of AVEO. “We believe this successful enrollment is a tribute to the differentiated safety and efficacy data of tivozanib observed in the Phase 2 trial. Based on achieving this milestone this early, we expect data from TIVO-1 to be available in mid-2011.”
Prior to launching TIVO-1, AVEO successfully completed a 272-patient Phase 2 clinical trial of tivozanib in patients with advanced RCC. Data from the Phase 2 trial showed that the median PFS achieved by patients with advanced clear cell RCC who had undergone a prior nephrectomy, the patient population also being studied in TIVO-1, was 14.8 months – comparing favorably to historical data from trials testing other currently approved multikinase inhibitors in RCC. Hypertension, which has been proposed as a biomarker of clinical effect among agents targeting the VEGF receptor tyrosine kinases in RCC, was the most commonly reported treatment-related adverse effect, and was observed in 50% of treated patients. In the Phase 2 study, development of hypertension was directly associated with improved clinical outcomes among patients overall and in the subset of patients with clear cell RCC who had undergone a prior nephrectomy. Off-target toxicities commonly associated with other targeted therapies, such as mucositis, fatigue and hand-foot syndrome, were notably low in the tivozanib group, which AVEO believes underscores a favorable tolerability profile and potential for combinability with other therapeutic agents.
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. The European Medicines Agency has granted AVEO orphan medicinal product designation for tivozanib for the treatment of RCC.
The company has initiated a series of clinical trials evaluating tivozanib in combination with other agents in multiple solid tumor settings, including an ongoing Phase 1b trial in combination with temsirolimus (Torisel®), an approved mTOR inhibitor, in patients with metastatic renal cell carcinoma; a Phase 1b trial in combination with the FOLFOX6 chemotherapy regimen in patients with advanced colorectal cancer and other gastrointestinal cancers; and, a Phase 1b trial in combination with paclitaxel (Taxol®) in patients with metastatic breast cancer. A Phase 1b trial evaluating tivozanib as monotherapy in patients with non-small cell lung cancer is also being conducted.
AVEO is also utilizing its Human Response Platform™ in its efforts to help identify rational drug combinations and patient populations most likely to be responsive to these combination therapies.
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 a highly differentiated 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 and has provided 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.
Forward Looking Statements
Any statements in this press release about our future expectations, plans and prospects, including statements about the potential for the TIVO-1 trial to provide the medical community with an accurate understanding of tivozanib efficacy and tolerability, the expected time when data from TIVO-1 will be available, the potential for tivozanib to have a favorable tolerability profile, tivozanib’s potential for combinability with other therapeutic agents, the potential breadth of tivozanib’s clinical utility, the proposal that hypertension could be biomarker of clinical effect among agents targeting the VEGF receptor tyrosine kinases in RCC, tivozanib’s ability to enable optimal inhibition of the VEGF pathway while minimizing side effects associated with off-target activity, AVEO’s cancer biology platform offering AVEO a unique advantage in oncology drug development and AVEO’s promising pipeline of antibodies, and other statements containing the words “believes,” “anticipates,” “plans,” “expects,” “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 positive results in our Phase 2 clinical trial of tivozanib may not be predictive of the results in our Phase 3 clinical trial; delays in data availability, or negative results from, TIVO-1, 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.
Monique Allaire, 617-299-5810
Caton Lovett, 910-232-7166