AVEO said it received preliminary feedback from the FDA and the regulatory agency recommended not filing the NDA at this time based on its assessment of the totality of evidence in the Phase III trial.
Shares of AVEO Oncology stock fell more than 36% in premarket trading after the company announced the U.S. Food and Drug Administration recommended the company not proceed with its New Drug Application for renal cell carcinoma drug Tivozanib.
In September, Cambridge, Mass.-based AVEO Oncology announced a secondary analysis from its Phase III TIVO-3 trial for overall survival benefits. The trial compared tivozanib to Nexavar (sorafenib). The company had been excited about filing an NDA for the drug, particularly after it had already seen one delay. During the Phase III study, tivozanib met its primary endpoint of demonstrating a statistically significant benefit in progression-free survival. However, a preliminary analysis of the secondary endpoint of overall survivability showed a hazard ratio greater than one. That prompted the FDA to recommend that the company not seek regulatory approval of tivozanib until “more mature” results regarding overall survival in patients were available. When the second analysis was conducted, AVEO said the data showed a hazard ratio of less than one and announced plans to file the NDA before the end of the year.
This morning though, AVEO said it received preliminary feedback from the FDA and the regulatory agency recommended not filing the NDA at this time based on its assessment of the totality of evidence in the Phase III trial. The FDA said it remained concerned about the results of TIVO-3 in the context of the overall development of tivozanib, AVEO said. 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,” AVEO said in its announcement. Additionally, the FDA said the median OS for tivozanib is worse than that of sorafenib, the company noted.
As a result of that feedback from the regulatory agency, as well as the changing first-line treatment landscape, AVEO said it will narrow its proposed indication to relapsed/refractory renal cell carcinoma. The FDA said that if AVEO wishes to proceed with a revised OS analysis in June 2020, AVEO should submit an updated statistical analysis plan (SAP) with a planned OS update based on the projected number of events at that time. And that, AVEO said, is what it will do. AVEO intends to submit an update to the SAP for the final OS analysis consistent with the discussions it had with the regulatory agency. AVEO will follow that up with the submission for its NEW Drug Application in the first quarter of 2020.
Michael Bailey, president and chief executive officer of AVEO, said he believes the company established an appropriate path forward for tivozanib, as well as a final analysis plan for overall survival.
“The continued separation of the PFS curves and the positive trend in OS HR observed from the first to the second interim analysis, together with tenfold more patients remaining progression-free and on tivozanib vs. sorafenib therapy, make us believe that the final OS results will not worsen,” Bailey said.
AVEO expects to report the final OS analysis in June 2020 based on a May 1, 2020 cutoff, at which point the company estimates that the study will have reached approximately 263 OS events, as discussed with the FDA. The FDA and the company agreed that if the final analysis yields an OS HR above 1.00, the company will withdraw its NDA application.
