Aveo Planning Tivozanib NDA Despite FDA Objections
A recent FDA-requested clinical trial did not alleviate an “overall survival (OS) trend” that the agency was concerned with in an earlier Aveo Oncology study of tivozanib in highly refractory metastatic renal cell carcinoma (RCC) patients, according to a company update. FDA told the company that it was premature to submit an NDA until additional data are available.
The TIVO-3 trial was designed to address FDA’s concerns about the OS trend in the TIVO-1 trial. “In the TIVO-1 trial, the company’s initial RCC pivotal trial, the FDA found that the inconsistent progression free survival (PFS) and OS results and imbalance in post study treatments made the trial results uninterpretable and inconclusive when making a risk-benefit assessment necessary for drug approval,” the update says.
During a recent meeting with FDA, the agency’ preliminary feedback recommended against an NDA submission based on current data, Aveo says. “The FDA noted that the company’s current interim OS results do not abrogate the FDA’s concerns over detriment and that those results may worsen with final analysis at 263 events, and that the median OS for tivozanib is worse than that of sorafenib [comparator],” it says. In view of the changing first-line treatment landscape as well as the FDA’s continued concerns, the company informed the FDA that it intends to narrow its proposed indication to relapsed/refractory RCC... The FDA said that if AVEO wishes to proceed with a revised OS analysis in 6/2020, Aveo should submit an updated statistical analysis plan with a planned OS update based on the projected number of events at that time.”
Aveo says it intends to submit an update to the SAP for the final OS analysis consistent with the recent discussions, followed by an NDA submission in the first quarter of 2020. Aveo expects to report the final OS analysis in 6/2020 based on a 5/1/2020 cutoff, at which point it expects that the study will have reached about 263 OS events. FDA and the company agreed that if the final analysis yields an OS HR above 1.00, the NDA application will be withdrawn, it adds.
Tivozanib is an oral vascular endothelial growth factor tyrosine kinase inhibitor discovered by Kyowa Kirin and approved for treating adult patients with advanced RCC in the European Union, Norway, New Zealand and Iceland. It has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers.