On January 31, 2019 AVEO Oncology (NASDAQ: AVEO) reported that it has accepted the recommendation of the U.S. Food and Drug Administration (FDA) not to submit a New Drug Application (NDA) for tivozanib (FOTIVDA) with the preliminary overall survival (OS) results from the Phase 3 TIVO-3 trial (Press release, AVEO, JAN 31, 2019, View Source [SID1234532989]). The FDA indicated that these preliminary OS results do not allay their concerns about the potential detriment in OS outlined in the complete response letter dated June 6, 2013. The Company now plans to make a NDA filing decision following the availability of more mature OS results.
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As disclosed in November 2018, a preliminary analysis of the secondary endpoint of OS in the TIVO-3 trial showed a hazard ratio (HR) > 1. The Company previously planned to conduct the final OS analysis in August 2019. Due to the longer-than-expected median OS in both arms, and following discussions with the FDA, the Company plans to designate the August 2019 OS analysis as interim. Results of this analysis are expected to be reported in the fourth quarter.
Since initially conducting the preliminary analysis of the OS endpoint in November 2018, the Company has identified the survival status of a group of patients that were previously lost to follow up. With the identification of these OS events, the October 4, 2018 preliminary OS HR was revised from 1.06 to 1.12. The Company has not performed any OS analyses beyond the preliminary October 4, 2018 data cut-off date.
AVEO intends to present detailed results of the TIVO-3 study, the Company’s Phase 3 randomized, controlled, multi-center, open-label study comparing tivozanib to sorafenib in 350 subjects with highly refractory advanced or metastatic Renal Cell Carcinoma (RCC) during an oral session at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) being held February 14-16, 2019 in San Francisco.
"We are hopeful that the positive PFS outcome will translate into an improved hazard ratio when we evaluate a more mature interim OS outcome in the fourth quarter of 2019," said Michael Bailey, president and chief executive officer of AVEO. "We look forward to continuing to work with the FDA to determine tivozanib’s benefit-risk profile as a single agent in RCC patients."
About Tivozanib (FOTIVDA)
Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models3, and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC. Tivozanib has been investigated in several tumors types, including renal cell, hepatocellular, colorectal and breast cancers.