CAMBRIDGE, Mass. (
) -- Next week is crucial for
(AVEO - Get Report)
On Tuesday, the FDA will post to its web site the agency's clinical review of Aveo's experimental kidney cancer drug tivozanib. Two days later, on Thursday, FDA will convene an independent advisory panel which will dissect the tivozanib data and vote on whether or not to recommend the drug's approval.
I believe the FDA briefing documents will raise significant concerns about tivozanib's efficacy in kidney cancer and the conduct of the pivotal phase III study. This will lead the panel to vote negative, meaning a recommendation against the drug's approval.
Admittedly, my conviction level for this prediction isn't all that strong. Today's FDA seems addicted to approving all drugs, so the agency may be unwilling to subject tivozanib to the scrutiny it deserves. If the FDA takes it easy on tivozanib, the advisory panel may do the same. Tivozanib demonstrated a statistically significant improvement in progression-free survival (PFS) over
Nexavar. This was the primary endpoint of the phase III study, so on this basis, the drug could get a positive vote.
[If you want a good read on the bull case for Aveo and tivozanib, check out the <a href="http://propthink.com/aveos-inflection-point-tivozanib-likely-to-receive-positive-advisory-vote-fda-approval/5898" rel="nofollow">column Aafia Chaudhry published yesterday</a>.]
I'm going to focus on the Aveo bear thesis. The problems with tivozanib -- and the reason why I'm predicting a negative panel vote next week -- lie deeper in the phase III data, specifically the lack of a survival benefit in the phase III trial. In February, Aveo presented a
poster on the overall survival data from the phase III tivozanib study
at a cancer research meeting.
Here's a chart depicting the overall survival analysis from the study, taken from that poster:
At the median, the difference in survival was just two weeks. Tivozanib-treated patients reported a median overall survival of 28.8 months compared to 29.3 months for Nexavar patients.
However, when overall survival in the study was analyzed over two years, the relative risk of death was 25% higher in the tivozanib arm relative to the Nexavar arm. [Hazard ratio = 1.245.] While survival trended against tivozanib, the greater risk of death was not statistically significant. That might work in Aveo's favor, but a hazard ratio of 1.245 against tivozanib is alarming -- even if not statistically significant -- and raises serious questions about the drug or the conduct of the study.