MarketFest, Part of the FDA's concern is due to the fact that the cellular effect being seen is as yet unexplained. In the conf call Dr. Stoll said that the FDA's general view is that "until we can get better explanations, we're going to have to stay conservative". One gets the impression that neither Cortex's histopathologists nor the FDA have seen cellular changes quite like this before (which is one reason why one might suspect the changes to be in the brain itself and not in say the liver, kidney, etc). So with the uncertainty over the causes of the cellular changes, the FDA is setting the safety bar for CX-717 higher than usual. Plus AMPA upmodulation is a brand new neurological approach, and the FDA probably remembers Lilly's difficulties with LY-451395 also.
Part of our problem in figuring the odds for CX-717 is that we have very little solid info to go on. Not only don't we know what the histo finding is, or in what organ it's seen, we have no idea what human dosing level is currently allowed by the FDA over various durations (1 month, 3 months). Is it 100 mg for 1 month, or 200 mg, or 500 mg or what? How about BID doses? Without this info we can't get a handle on how much dose liberalization we'll need to get from the FDA for CX-717 to be viable for further studies and for partnering/outlicensing.
Concerning 800 mg BID specifically, this was the highest BID dose given in the Phase 1, in effect the "MTD", though they never did get any serious adverse events, only an increased frequency of headaches (1600 mg was called the single dose MTD). With the dosing of CX-717 being restricted by the FDA (how restricted we don't know), it seems very unlikely that the FDA would allow BID dosing for any length of time at the MTD.
