3:22 PM
 | 
Nov 06, 2018
 |  BC Extra  |  Clinical News

Aveo RCC compound trends toward detrimental survival effect, again

Despite announcing plans to submit an NDA to FDA for its renal cell carcinoma compound in about six months, Aveo Pharmaceuticals Inc. (NASDAQ:AVEO) lost $0.51 (20%) to $2.03 on Tuesday after reporting preliminary data late Monday that showed no overall survival benefit for Fotivda tivozanib as a third-line treatment vs. Nexavar sorafenib in the Phase III TIVO-3 trial (HR=1.06, p=0.69). The company designed TIVO-3 to address a 2013 complete response letter for Fotivda in which FDA expressed concern about a negative OS trend seen in the first Phase III trial, TIVO-1.

Aveo said data for OS, a secondary endpoint, from TIVO-3 are not yet mature. Final survival data are expected in August 2019, which would be about three months after Aveo's planned NDA submission. The company also said it will request an end-of-Phase III meeting with FDA as early as next week to discuss the data and its submission plans.

Fotivda did meet TIVO-3's primary endpoint of improving median progression-free survival (5.6 vs. 3.9 months, HR=0.74, p=0.02) and the secondary endpoint of improving overall response rate (18% vs. 8%, p=0.02) vs. Nexavar.

In May 2013, FDA's Oncologic Drugs Advisory Committee voted 13-1 against approval of Fotivda as first-line treatment of RCC based on data from TIVO-1 alone. While Fotivda met TIVO-1's primary PFS endpoint, the panel was concerned that the OS analysis showed a trend towards a detrimental effect on survival with Fotivda compared with Nexavar (median OS of 28.8 months vs. 29.3 months, HR=1.25, p=0.11). In briefing documents released ahead of the meeting, FDA reviewers said that while six of the seven RCC drugs at the time were approved based on an improvement in PFS, all seven had an estimated HR for OS of less than 1.

FDA issued a complete response letter the next month, citing inconsistent PFS and OS results from the single TIVO-1 trial (see "Aveo Receives Complete Response for RCC Therapy").

The open-label, international TIVO-3 trial enrolled 351 patients with refractory advanced or metastatic RCC who failed at least two prior regimens to receive Nexavar or once-daily oral Fotivda.

Fotivda, an inhibitor of VEGF receptors 1, 2 and 3, is approved in Europe to treat advanced RCC.

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