AV-951 Demonstrates Prolonged Progression-Free Survival and Excellent Safety Profile in Patients with Advanced Kidney Cancer; Phase 2 Data Presented at ASCO
Results Show Median Progression-Free Survival of 11.8 Months; Tivozanib Designated as Generic Name for AV-951
CAMBRIDGE, Mass., May 29, 2009> – AVEO Pharmaceuticals, Inc., a biopharmaceutical company leveraging breakthrough discoveries in cancer biology to discover, develop and commercialize targeted oncology therapies, today announced additional data from its Phase 2 clinical trial of tivozanib (AV-951) - its oral, triple VEGF receptor inhibitor - in patients with advanced renal cell carcinoma (RCC). These data are being presented today at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), abstract number 5032.
The median progression-free survival (PFS) achieved by patients in this Phase 2 trial (N=272) was 11.8 months. The median duration of response had not yet been achieved at the time of this analysis and patients remaining on tivozanib continue to be followed.Final overall survival data are awaited.
The safety profile of tivozanib observed in the trial was particularly notable for the minimal off-target toxicities often associated with other targeted therapies, such as mucositis/stomatitis (4.4%, no Grades 3/4), hand-foot syndrome (3.0%, no Grades 3/4) and fatigue (9.9%; 1.5% Grade 3, no Grade 4). The most common treatment-related adverse events seen in the trial were hypertension and dysphonia (hoarseness of voice), both of which were readily manageable and are recognized as “on-target” effects expected of a highly potent and selective VEGF receptor inhibitor. AVEO expects to initiate a Phase 3 trial of tivozanib in advanced kidney cancer later this year.
“Despite significant advances in treatment for metastatic renal cell carcinoma, there remains a need to develop new, more effective therapies with improved tolerability,” stated Robert Motzer, M.D., attending physician at Memorial Sloan-Kettering Cancer Center. “The favorable tolerability, combined with the extended median progression-free survival, demonstrated by oral tivozanib in this ‘real world’ population indicates a highly differentiated VEGFR profile and signals an exciting development for patients battling advanced kidney cancer and potentially other cancers influenced by the VEGF pathway.”
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. Given the long half-life (five days) of tivozanib, patients received treatment once daily for three weeks followed by one week off (one cycle over four weeks). All patients enrolled in the trial received open-label tivozanib for 16 weeks, after which patients with progressive disease (N=21) discontinued treatment, patients with greater than a 25 percent decrease in tumor volume (N=76) continued on tivozanib and patients with stable disease (N=119) were randomized to either tivozanib or placebo. Response was determined according to RECIST (Response Evaluation Criteria In Solid Tumors), a set of published rules that defines when cancer patients improve (respond), stay the same (stable), or worsen (progress) during treatment. The primary endpoints of the trial were objective response rate at 16 weeks, percentage of patients who were progression free at 12 weeks following randomization (i.e., 28 weeks after study entry), and safety.
With a median duration of therapy of 7.4 months, highlights from the analyses as assessed by independent radiological review unless otherwise noted include:
• Median PFS of 11.8 months
• Objective response rate of 25.4%
• Disease control rate was 84.2%
• Percentage of patients progression free at 12 weeks following randomization (investigator assessed):
o 58.6% tivozanib
o 37.7% placebo
• Tivozanib therapy demonstrated an excellent safety profile
“AVEO Pharmaceuticals is committed to developing novel, next-generation therapeutics that are highly effective at treating cancer without the toxic and regimen-limiting side effects widely associated with traditional therapies and even the newer targeted therapies,” stated Tuan Ha-Ngoc, president and chief executive officer of AVEO Pharmaceuticals. “A growing body of clinical data suggests tivozanib is emerging as a highly differentiated VEGF-targeted kinase inhibitor due to its excellent tolerability profile and low incidence of ‘off-target’ toxicities commonly associated with other well established and investigational TKIs. We believe that with tivozanib patients will no longer have to compromise between a high degree of efficacy and tolerability.”
Due to the favorable side effect profile of tivozanib and its potential broad applicability across many tumor types, AVEO has implemented a robust development program in support of tivozanib. The company has already initiated a series of clinical trials evaluating tivozanib in combination with other agents in multiple solid tumor settings, including a Phase 1b trial in combination with temsirolimus (Torisel™), an approved mTOR inhibitor, in patients with mRCC; 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/2a trial in combination with paclitaxel (Taxol™) in patients with metastatic breast cancer. A Phase 1b/2a trial evaluating tivozanib as monotherapy in patients with non-small cell lung cancer is also being conducted. A Phase 3 trial of tivozanib in advanced kidney cancer is expected to begin later this year.
In addition, researchers presented data at the American Association for Cancer Research (AACR) 100th Annual Meeting in April 2009 from its proprietary preclinical models which demonstrates robust inhibitory activity of tivozanib in its novel, genetically engineered model of hepatocellular carcinoma (HCC), the most common form of liver cancer. Based on these data, AVEO believes HCC represents another potential opportunity for clinical development.
About the Phase 2 RCC Study
This Phase 2 placebo-controlled, randomized discontinuation trial assessed the efficacy and safety of once-daily, oral tivozanib in 272 metastatic renal cell carcinoma patients naïve to VEGF targeted therapy at more than 30 sites in Europe and India under a U.S. investigational new drug (IND) application. In this trial, all patients received 1.5 mg/d of tivozanib (three weeks on, one week off) for the first 16 weeks, after which time patients were evaluated for response. Those patients who achieved >25% tumor regression remained on therapy, while patients who experienced <25% change from baseline were randomized to receive tivozanib or placebo in a double-blind fashion. For more information, please visit the NIH clinical trials website at http://www.clinicaltrials.gov.
About Renal Cell Carcinoma
Advanced RCC, a rare but serious type of kidney cancer, is among the most treatment-resistant tumors. Worldwide incidence of RCC is more than 200,000 cases annually. Recent estimates show that nearly 36,000 people in the U.S. developed RCC in 2006, and approximately 12,500 died due to progression of the disease. Although first-generation multikinase inhibitors are available for the treatment of RCC, there remains a significant need for improved therapies with greater tolerability.
Tivozanib (AV-951), an investigational new drug, is a novel, highly potent and selective inhibitor of VEGF receptors 1, 2 and 3, exhibiting picomolar inhibitory activity against all three receptors. Angiogenesis inhibition has demonstrated benefit for patients with a wide range of cancer types, including renal cell carcinoma, metastatic breast cancer, colorectal cancer, and non-small cell lung cancer. Due to its potency and specificity, AVEO believes tivozanib may enable maximal inhibition of the VEGF pathway, while avoiding 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. In addition, AVEO has evaluated tivozanib using its Human Response Platform (HRP™), a unique set of engineered tumor models that provide further insight into potential clinical settings, combinability with other anti-cancer agents, tumor subtypes and responsive patient populations.
AVEO recently completed a Phase 2 placebo-controlled, randomized discontinuation trial assessing the efficacy and safety of once-daily, oral tivozanib in renal cell carcinoma (RCC). In addition, AVEO is currently conducting multiple ongoing clinical trials of tivozanib including a Phase 1b trial in combination with temsirolimus (Torisel™), an approved mTOR inhibitor, in patients with mRCC; a Phase 1b trial in combination with the FOLFOX6 chemotherapy regimen in patients with advanced colorectal cancer and other gastrointestinal cancers; a Phase 1b/2a trial in combination with paclitaxel (Taxol™) in patients with metastatic breast cancer; and a Phase 1b/2a trial as monotherapy in patients with non-small cell lung cancer.
AVEO is a late-stage biopharmaceutical company focused on the discovery and development of novel, targeted cancer therapeutics. AVEO’s proprietary, integrated cancer biology platform enables the company to pursue highly efficient drug development strategies in oncology that increase the probability of clinical success and provides a discovery engine for high-value targets and therapies. This approach has resulted in a balanced pipeline of novel cancer therapies focused on well-validated targets (VEGFR, EGFR) and promising novel targets (HGF, FGFR, ErbB3 and NOTCH), as well as collaborations with Eli Lilly, Merck, OSI Pharmaceuticals, Schering-Plough and Biogen Idec. The company’s lead product, tivozanib (AV-951), a triple VEGF receptor inhibitor, recently completed Phase 2 clinical development in patients with metastatic renal cell cancer and is expected to enter Phase 3 development in 2009. Through a combination of internal drug discovery and selective in-licensing of targeted therapeutics, AVEO is building a diversified product pipeline and moving toward its vision of becoming a fully integrated biopharmaceutical company. For more information, please visit the company's website at www.aveopharma.com.