AVEO Announces Clinical and Regulatory Updates for Tivozanib

AVEO Oncology has announced clinical and regulatory updates for its lead drug candidate, tivozanib, an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI).

The Company announced today that its pivotal, Phase 3 TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC), is enrolling substantially ahead of schedule. The Company now expects TIVO-3 to complete enrollment in June 2017, ahead of its prior guidance of August 2017. Because the study is event driven the Company is not revising the anticipated time to topline data at this time, which is currently expected in the first quarter of 2018. TIVO-3 is expected to undergo a pre-planned futility analysis around midyear. The TIVO-3 trial, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support first and third line indications for tivozanib in the U.S.

The Company also announced today that the Phase 1/2 AVEO-sponsored TiNivo trial evaluating tivozanib in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, Opdivo® (nivolumab), in advanced RCC, is scheduled to open sites for enrollment in early March, with dosing of the first patient expected in the same timeframe. The company received approval by the French National Agency for Medicines and Health Products Safety (ANSM) to initiate the study and is currently labelling the nivolumab supply provided by Bristol-Myers Squibb for use in the trial. The study, which will be led by the Institut Gustave Roussy in Paris, is under the direction of Professor Bernard Escudier, MD, Chairman of the Genitourinary Oncology Committee. The Phase 1 trial will evaluate the safety of tivozanib in combination with nivolumab at escalating doses of tivozanib and, assuming favorable results, is expected to be followed by an expansion Phase 2 cohort at the established combination dose.

AVEO also announced today that its European licensee for tivozanib, EUSA Pharma, a specialty pharmaceutical company with a focus on oncology and oncology supportive care, has received the Day 180 List of Outstanding Issues (LOI) from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). The Day 180 LOI signifies that the Marketing Authorization Application is not approvable at the present time, and outlines outstanding deficiencies, which are then required to be satisfactorily addressed in an oral explanation and/or in writing prior to a final application decision. EUSA has informed AVEO that it expects to submit written responses to the Day 180 LOI in April 2017, and the EMA has tentatively scheduled EUSA to provide an oral explanation to the CHMP at its May 2017 meeting.

"We continue to execute on the TIVO-3 and TiNivo studies in our effort to complete our U.S. pivotal clinical strategy, as well as support EUSA Pharma in its response to European regulators," said Michael Bailey, president and chief executive officer of AVEO. "The rapid pace of enrollment in our TIVO-3 study is a testament to the broad level of support and enthusiasm for tivozanib among investigators. Fundamental to this drug candidate’s unique profile would be its potential to be safely combined with PD-1 immunotherapies, and we look forward to initial results from the Opdivo® combination TiNivo study in RCC in the first half of 2017."