Looking at this another way, one can argue Aveo gave some 500 RCC patients their only chance to have access to effective drugs. Hardly unethical, when otherwise most would not have had that care. Result was the best and second best OS in RCC ever measured. As for OS vs. PFS, why does a Pazdur value the last two weeks of a slow death more than a patient's significantly longer "more stable" period free of renal cancer progression? Can't be that extending the last few weeks by another few weeks can be the most profitable time for the hospital, can it? That would be unethical... Pazdurs should let the patients choose.
I am trying to think of the many ways I could describe my feelings about Pazdur, the words/phrases, phony, liar, patient killer, self-important and POS come to mind. Can't forget destroyer of jobs and shareholder value after patient killer.
If you assume the drug is effective based on increasing OS times over other trials (especially since those trials had subsequent secondary treatment that increases OS unlike TIVO-1), and that the EMA will not care that the trials were not done in the US like the FDA is decreeing as required, and that at least a condition approval by the EMA is likely, the FDA does have some motivation to work with AVEO to approve tivozanib. The FDA is benchmarked against the EMA regarding length of time of drug approval and if they uphold the ODAC recommendation, it will negatively impact this metric. The FDA already has a miserable record in medical device approval- almost all medical devices are first launched in the EU, and if they can’t get past the trial issues with AVEO, I think it would set precedent for incremental improved drugs (ones not tested against a placebo but an active approved drug) to be first tested and launched in Europe. The FDA should work with sponsors to overcome the disadvantages the US has with time and costs, rather than impose stronger restrictions- as its mandate is to reduce the risk of unsafe ineffective drugs in the US, not increase the barriers for safe and effective drugs- even if they don’t think the risk/benefit standard is met due to lowered incremental benefit of the drug (enforcement of the risk/benefit stance is not part of their legal mandate. Per their mandate on a well-controlled study: (iv)Active treatment concurrent control. The test drug is compared with known effective therapy; for example, where the condition treated is such that administration of placebo or no treatment would be contrary to the interest of the patient. An active treatment study may include additional treatment groups, however, such as a placebo control or a dose-comparison control. Active treatment trials usually include randomization and blinding of patients or investigators, or both. If the intent of the trial is to show similarity of the test and control drugs, the report of the study should assess the ability of the study to have detected a difference between treatments. Similarity of test drug and active control can mean either that both drugs were effective or that neither was effective. The analysis of the study should explain why the drugs should be considered effective in the study, for example, by reference to results in previous placebo-controlled studies of the active control drug.)
By the way, Astellas is expected to file the MAA with the EMA in 3rd or 4th quarter 2013, and make a $15M milestone payment to AVEO when they do. While the US outlook looks bleak due to the FDA, the EU does not, and for a $2.5 stock with $3 in cash, having split income from sales in Europe with Astellas in 2014 makes the stock undervalued. Obviously, when there is more European data available post launch, the risk is reduced, and the FDA ought to be able to leverage the European data and the EMA to schedule a delayed FDA approval rather than suggest a new trial that takes years and is very costly and has to be added to the costs of drugs in the US. What they are doing with the current approach is increasing drug costs and decreasing speed to market and in effect, preventing the best drugs from being available in the US.
FDA clearly feels that given the number of available treatments, they won't approve a drug with a flawed application and a confusing study. Why risk that? This and all the other bad news is known to the entire world, e.g. incompetent management who were overly confident in the drug and burned too much cash. The stock price today is factoring in a total loss on Tivozanib, which I think is a mistake. I don't pretend to know what will happen, but it seems to me that the bad news is out in a big way, and that means the stock is probably a good buy here well below BV and cash. If management were to clearly show us that the fog has lifted and that they clearly understand the path forward, then this stock could easily go back to $7 in a year or so. A statistically sound solid second PIII that Astellas commits to would take the stock to $4.5. And that could happen by August or September.
I might agree with your end scenario, but your preamble is not all accurate, Aveo used some 300 m (only!) to get to an FDA-accepted NDA and have cash to spare. Hindsight shows they cut corners, but not to the detriment of patients, imho. They met the primary endpoint ok, but maybe they did not figure on there being such a crowded RCC-space by that time.