Aveo Oncology has scrapped plans to file for approval of tivozanib using preliminary overall survival data after talking to the FDA. The agency advised Aveo against filing a NDA after data failed to address the concerns that led it to reject the drug in renal cell carcinoma in 2013.
The FDA hit Aveo with a complete response letter in 2013 after an advisory panel criticized the design of the pivotal trial and questioned the benefits of the VEGF inhibitor in light of its failure to beat the overall survival achieved by Bayer’s Nexavar. Aveo responded to the setback by initiating another clinical trial designed to alleviate the concerns of the FDA and its advisers.
Aveo posted top-line data from the trial in November. The readout included a preliminary look at the critical overall survival endpoint. Aveo thought the data may enable it to file for approval around May. The FDA thought differently.
In a statement to disclose the news, Aveo said “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 preliminary OS data showed no statistically significant difference between Nexavar and tivozanib. And after the recent addition of patients previously lost to follow up, the hazard ratio worsened from 1.06 to 1.12.
The FDA’s position means Aveo will need to wait until it has mature data to file for approval. It is unclear exactly when Aveo will have the required data. In November, the biotech scheduled the final analysis for August. However, talks with the FDA and “longer-than-expected median OS in both arms” have led Aveo to plan to designate the August assessment as an interim analysis.
Aveo expects to have the results of the analysis in the fourth quarter, but at that stage it will have a “more mature interim OS outcome,” CEO Michael Bailey said in a statement, not the final readout it may need to alleviate the FDA’s concerns.
Shares in Aveo fell 60% following the news.