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No need to apologize--I wish I was more sure of the answers. One thing I am not sure about is: What proportion of people who apply to be in the study will turn out to have clearcut sleep apnea, which is consistent in terms of apnea episode frequency over time? DavidAl might know....
But this means we do not know how many people have to be screened (and fees paid for) in order to get n=20. We also don't know if they are going to require that at least a couple of them have a diagnosis of central/mixed apnea--which is about 15% of the apnea population, since CX717 might work differently in that population than in obstructive sleep apnea. This is why I am reluctant to presume/predict a shorter timeline.
Secondly--why on earth would you assume that a CRO would accept deferred payment? If anything, in dealing with a company running out of money, they don't want to end up one of the unpaid creditors, so they probably want most of the money as contracted elements of the study are completed.
I don't know what the cost of the study is, but I'd bet it's closer to a million dollars than $600K. It's hard to go wrong guessing on the high side in the pharma world.
NeuroInvestment
A couple of points: per patient cost is far higher than just sending a patient to a sleep lab for one night. They are going to send them three times, the first two to make sure that they have sleep apnea, and that the apnea episodes are similar in frequency each time. A patient whose apnea varies would muck up their results. This also means they will be running patients in the first one or two sleep lab nights who won't be eligible for the study itself--the third night, when patients get drug or placebo. It is also being run by a clinical research group, who gets paid to deal with patient entry, evaluation, data collection and blinding. Having a CRO at least doubles the cost based on my past experience--but if you dont have inhouse staff to run a trial, and Cortex doesn't, there aren't any options. I figure $10-20,000 per patient enrolled, plus some costs for the patients who are not enrolled but are assessed.
They might have the money to run the trial in and of itself--but they have to keep the lights until the trial is done--and if they lay everyone off, they won't have a company to run even if they have good data. There is the possibility they could run a few patients, see the blinded data shows a big change, and take the risk of unblinding and trying to do a deal based on that. But they cannot go into the trial assuming that. They have to assume that the trial goes the full duration, and that they then need the time to partner.
For this they need money.
Which I continue to believe they will get.
NeuroInvestment
We'll just have to disagree on how far out in time the business planning should go and whether these deals are not far-sighted enough. I don't think either of us is going to convince the other.
NeuroInvestment
Well, the Merck deal certainly muddies Schering-Plough's focus on relatively small matters, and their interest in making announcements. The people within SP who were most connected to those trials (who used to work for Organon), having survived one merger, may be preoccupied with whether they will survive this one, or be included in the 16,000 jobs to be culled. It doesn't mean everything has ground to a complete halt, or that any and all licensing activities are frozen, but it would be human nature for those people to have their attention diverted.
NeuroInvestment
One thought that comes to mind is that the Organon partnership was signed when their cash had dwindled to the point that they couldnt have met their next payroll. Since they are approaching that point in the next month or two, and even though the Organon deal would seem like ancient history, perhaps they don't want anyone to know what they were willing to settle for back then, under those circumstances, particularly in terms of milestones (the royalties have been described as double digit).
NeuroInvestment
I'm happy to see Hamburg instead of Nissen as well, since the latter would probably have a tendency towards showboating at industry's expense.
I doubt that Waxman's five year patent life proposal will survive intact, but any marked limitation will make biologics development less appealing, which is a mixed bag. At the moment, many companies are thinking of biologics as their hedge against generic competition, which is problematic for brain disorders, since getting biologics into the brain is so difficult. In order to keep resources allocated for CNS, limiting biologic patent coverage might help sustain attention on, and investment in, small molecule drugs aimed at CNS disorders.
NeuroInvestment
Good point. Cortex, not UC, licensed that work from Greer/U. Alberta.
NeuroInvestment
This came up previously, perhaps 18 months ago. Cortex controls the compounds developed inhouse. As was also discussed a while back, University of California had to agree to extend the timeline on Cortex's license, and chose to do so (I think this was in 2007). So the UC's judgment was that they were better off with Cortex working to commercialize the IP than trying to find someone else to do so (and without access to Cortex-owned compounds).
NeuroInvestment
That's been discussed thoroughly. Now we have to see which scenario unfolds.
NeuroInvestment
I never said Lilly demonstrated 'superior capability.' They liked thinking they were superior, but as Gfp points out here, it turned out their platform had all the superiority of a certain unsinkable ocean liner in 1912. Their results in an animal model of Parkinson's were very impressive, but their compounds historically have not been viable in humans due to toxicity problems. There has never been a head to head (rodentwise, as it were) to 'compare' high-impacts. I don't know if Les Street has really solved the high-impact puzzle, but there's no evidence as of yet that Lilly has either. This is all yet-to-be-determined. And Cortex's immediate future does not rest on how the high impacts fare.
NeuroInvestment
OK, now I remember the reference. Your memory is better than mine. I wasn't sure what to make of that straw poll, and I havent heard anything since to confirm--or disconfirm any interest on their part.
Reckitt Benckiser did express interest. However I now know (as of this am, in fact) that the budget for the pharma side has been severely cut back, so I don't know if they are really a player here or not.
NeuroInvestment
Wait--I noted that Lilly has a AMPA modulator history and their former CNS head now runs neuroscience at Merck--but he is a mGluR specialist, which is an alternative way to upramping glutamatergic activity. And those who have followed the board for a couple of years may recall that when I buttonholed a Lilly exec back in--2006? maybe--he said that Lilly felt they could beat Cortex, and thus didnt see any need to ally with them. Of course, that's an eternity even in pharmatime, so who knows what the current attitude might be. But I did not say Lilly or Merck have "an interest in AMPA programs @COR", at least other than as a competitor to be monitored. They might, but I have no information to that effect.
Your point about the financial markets having changed is very on-target: when trying to predict what will happen, partnership timelines and terms, and what different events might translate into for share price: We are in uncharted territory, for both micro and macro events. No one 'knows' what's going to happen, because no one has been here before.
NeuroInvestment
Gfp:
As I posted last week, the deals I have seen have been priced at 'average of closing price for five days'--so if a financing was done today, it would be around 30 cents. They have also been pretty 'vanilla', comprising those shares plus warrants.
I wasn't particularly predicting a certain number of shares, just noting the stakes involved in their pricing. Your point about the authorized share limit is very pertinent.
While the share price is appalling, the idea of raising 'only' $5-6 million is not in itself abhorrent. That plus a modest RD deal would give them enough runway to get a SA deal IF those data are positive.
NeuroInvestment
<<as due dilligence nears completion, news of an impending deal tends to leak out. Obviously, based on share-price, such leakage isn't happening. Can we infer from this that a deal is months rather than weeks away?>>
I recall arguing the contrary, that Big Pharma people aren't going to risk their jobs, and Cortex has already shown the ability to keep (RD results) quiet. I think the share price movement is mostly due to anxiety about "going broke", plus the possibility that people involved with companies (I know of two) interested (not committed) in doing a financing, could be keeping the share price down to make the terms as advantageous as possible. This has been questioned by some, and I certainly don't 'know' that anyone is doing this. But when they talk about 'motive', that would be a pretty compelling one (does a company receive 33 million shares plus warrants or 25 million shares plus warrants for their $10 million?)....that's enough to at least raise the possibility of cheating.
So I personally only take this from the "hue of darkness" (nice touch there) surrounding negotiations (which are not "purported")--nothing is settled. It says nothing about whether it would take days, weeks, or months to get things settled. Other than we know that Cortex doesn't have 'months.'
NeuroInvestment
I know from direct conversation with one of the three companies 'going in another direction' that they in fact were looking at 717/RD, at least they were a month ago. That doesn't mean that they are making offers, but they were at least doing DD. So there are no absolutes, even in the companies who seem to be moving away from CNS.
If I were developing a roster of companies still possibly in RD play, I'd include the mid-size companies who make a lot of revenue from hospital based sales; the several other companies not included in the three mentioned that have significant pain franchises.
Sleep apnea is a different, larger, indication which requires a neurology sales force that could target outpatient sleep centers. Cephalon would now seem unlikely given the number of acquisitions they've made lately. Big Pharmas with insomnia drugs would be a start, Pfizer would not be included, since they were so burned with indiplon.
Finally--I personally do not assume that no discussions are yet possible for ADHD even though they don't have POC for CX-1837. Schering-Plough has an interest obviously, and I would not assume that the buyout offer precludes relatively small expenditures (I'm sure the contract precludes anything significant). Shire (Adderall/Vyvanse) and Novartis (Concerta) have substantial interests (especially Shire) in ADHD.
This is less likely, but possible.
The least likely, albeit not totally impossible, would be a deal related to neurodegeneration. But without a high impact with any human data, that is highly unlikely, unless it was on really lousy terms.
So I am not yet assuming that a PIPE is now sure to be the next step. Still roughly 50/50.
NeuroInvestment
Nauseating. Consolidation/amputation as the unthinking substitute for strategic investment.
As Dew (who I suspect would not agree with the above statement) did indicate, 'Ampakines' played zero role in whatever calculations went into this plan--which is all about shoring up products-on-the-market in the face of patent expiration.
The only positive fact is that to the degree to which SP may be looking at an Ampakine licensing, such a deal is so small that it probably would not be affected much by a merger. Had SP been thinking about acquiring Cortex, which I don't think is the case, that would be derailed, but not tiny licensing deals. Reviewing all of the neuroscience programs to decide what to cull or keep is probably a year away.
Merck has not been an ADHD player, so this can't be seen as a plus for Org-26576, though if data is positive, it could still be brought ahead. Darryle Schoepp, who I know slightly, is Merck's head of neuroscience, and is a mGluR specialist. He is acquainted with Ampakines, since he was previously at Lilly, and he is at least obliquely acquainted with Cortex, since he has been a NI subscriber for many years.
Bottom line for Cortex: Cortex/Ampakines constitute such a small issue that, if either Merck or Schering (far more likely the latter) had a licensing interest in ADHD, this would not necessarily interfere with it much, though for Cortex, even a few weeks of delay is now relevant. Neither company would likely have been a RD/sleep apnea partnering candidate, so this is probably a nonfactor therein.
But this merger will keep larger companies running around like barflies at last call trying to figure out who to hook up with before closing time. A real waste of effort, and reflecting a profound dearth of creativity.
NeuroInvestment
You piqued my curiosity with that. The only proxy statement immediately at hand was 2007: Basic pay is $3000 per meeting, there were small supplements for committee assignments. In 2006 BOD members earned $13,500 to 19,000 for the year. I doubt it was much different in 07 or 08.
NeuroInvestment
Athero: On second thought, given the adverse event profile (can you believe the FDA allows this stuff to be sold?) I'll just stick with having a subpar level of common sense. Why change now?
NeuroInvestment
Point taken. It was quite early out here (6 am or so) and my common sense filter had not yet been activated by caffeine. I realize that some will now suggest that I clearly need to up my expresso intake on an ongoing basis....
NeuroInvestment
Gary Lynch probably submitted that paper (which covers work in his lab, albeit licensed to Cortex) to PNAS at least two or three months ago (the actual date would be with the article, which I havent yet looked at). It was finally published, and thus ready to be announced. Whether it is material at the moment may be debatable, but it happened, it's of interest. Are you suggesting Cortex (which devoted fifteen minutes to providing a quote and having the PR company produce a release) should have ignored it?
NeuroInvestment
"...Couldn't resist pointing out that we are on our way to much lower lows" would be an eminently resistible verbalization if you actually owned any and aspired to selling it.
My supply of "unsold NI articles" is exactly the same as your portfolio of Cortex stock--zero.
NeuroInvestment
Coleman is also the person who is most directly in contact with other pharmas regarding partnering. The fact he made purchases meant nothing was signed or certain, but the fact that at age 67 he was putting more money into Cortex certainly doesn't indicate that he was not seeing interest.
BTW--In spite of having too much Cortex stock by any measure of diversification, I couldn't resist buying some today. And I am having a hard time getting the order more than 40% filled. I don't actually believe Iggs owned any, but if he did, buying some of it at this price will be even sweeter.
NeuroInvestment
Actually, even R&R doesn't appear to be doing much business of late. And Elemer Piros' assistant Raghuram Selvaraju has gone off to cover mainly Big Pharma for another outfit.
So my point was that even a relative nonentity such as myself is in this very weird position of watching companies slowly drown, while trying to be helpful in the most minuscule fashion.
And while Cortex appears to be experiencing 'capitulation' on someone's part today, I strongly believe they will not be among those who go under. Not that saying so will provide much solace until their fiscal timeframe stops being defined in 'weeks,' via a financing or deal.
NeuroInvestment
I wish. I'm saying that I've told a couple of small microcaps who are in worse financial shape than Cortex that they can pay their bills if/when they raise money.
NeuroInvestment
I took a quick look at the roster of all forty (ten per therapeutic area) companies that were on the Windhover 'Top 10'
lists last November. I didnt go and check each company on the non-neuro lists, but to the degree my recognition memory still functions, I don't believe any of them have signed a partnership in the ensuing (almost) four months.
Whether this represents an overall shift in strategy amongst Big Pharma is questionable. As I posted before, there was a period of 2-3 months this (almost) past winter where everyone seemed pretty paralyzed. Unless a deal had already been nearly completed, everyone was afraid to spend in such a chaotic environment. I saw a 50-60% decrease in revenues, a BP consulting contract suddenly vaporize, it was a nuclear winter for a while. I am extending credit to some microcaps who can't pay their bills, ironically enough.
There has been some thawing of late, as if pharma has realized life must, and will, go on. But this simply means stasis has transformed back into Pharma's usual glacial pace.
NeuroInvestment
The three or four financings I have seen in the past couple of months, and the names slip my mind ( they have been non-neuro, other than Clinical Data, and that was Randall Kirk selling an offering to himself) have all been, so far as I can recall: X million shares at average price of five days prior to completion, plus the same number of shares via warrants exercisable at a price slightly above the price at which the financing was executed. Dew tracks this over a wider universe than I do, if he looks in, he may have more information about trends.
NeuroInvestment
<<Neuro, doesn't this look doable? >>
Before you get too excited, this is fairly old data, reported in December 2007. The events thereafter were interesting: Here is the sequence as was summarized in NI February 2008:
<<Epix's Epic Embarrassment
"Michael G. Kauffman, M.D., Ph.D., chief executive officer
of EPIX Pharmaceuticals stated, “We are very excited
by the measurable impact on memory and cognition,
achieved in such a short period of time, in a trial that was
designed primarily to assess safety and tolerability."
--Press release from Epix Pharmaceuticals, 12/18/07
"When things seem to be too good to be true, they usually
are (too good to be true): Epix's Alzheimer's trial for its
5HT-4 drug PRX-03140 showed an amazing 5.7 point
ADAS-cog improvement in just two weeks...albeit in just
one 10 patient dose cohort, with two 14 point responders,
the mean change for the others was 3.3 points, and the
other six cohorts did not show significant benefit. And
there was no benefit if the patients also received Aricept-
-Epix states that these patients hadn't been washed out,
and thus were already at the cholinergic ceiling (dubious
trial design and execution). But other than that, these
were revolutionary results. So revolutionary, in fact,
that NI strongly doubts that they will be replicated.
Because they are not only revolutionary, they make no
sense."
--NeuroInvestment 1/06/08
"The updated results described below reflect the
correction of previously undetected errors that were
included in the trial results as provided to the company
from a third party contract research organization (CRO)
and as reported by the company in a recent press release,
as well as newly available data on other measures of
cognition.
As a result of errors made in the transcription of data and
calculation of the Alzheimer’s Disease Assessment Scale
cognitive subscale (ADAS-cog) score, an independent reanalysis
of the data has been conducted. The corrected
results show that patients receiving 150 mg of PRX-03140
orally once daily as monotherapy achieved a mean 3.6
point improvement on the ADAS-cog versus a 0.9 point
worsening in patients on placebo, which continues to be
statistically significant (p= 0.021).
--Press release from Epix Pharmaceuticals, 1/15/08
"Oh. That's very different. Never mind."
--Gilda Radner 1976
Perhaps in the future, if circumstances warrant, Epix will
conduct the "independent re-analysis' of suspect data
before broadcasting them. (NI February 08)>>
Basically, so far as I can tell, no one takes even the corrected data all that seriously. Between statistical incompetence and flukiness, this is not something that anyone should aim to emulate.
BTW--the CEO was subsequently fired. Replaced by interim CEO Elkan Gamzu, who I know well from Cambridge Neuroscience and Pharmos. And now they are presenting 16 month old data for lack of anything else to say.
NeuroInvestment
I am completely baffled as to what about those statements was 'disingenuous.' But sorting that out is probably not worth the time.
NeuroInvestment
FWIW: This is what NI March has to say about this kind of Big Pharma substitute for strategy:
<<March of the Lemmings, 2009 Edition
In the face of patent expirations, pricing pressure, unproductive pipelines, and more than a little antipathy from Congress and its constituents, Big Pharma companies have begun unveiling their various Strategic Visions for 2009 and beyond:
1) If You Can't Beat 'Em, Join 'Em. In an era wherein generic manufacturers prepare to club Big Pharma senseless with compounds that they themselves developed, some Pharmas have decided that turnabout is fair play, and they are going to enter the generics business themselves. Where we presume they will club themselves senseless. Those companies who forget that imitation is a strategy with an expiration date will eventually be leapfrogged by those who come up with novel compounds which improve on what has gone before. Generic risperdal and olanzapine will lose a lot of their pricing clout, and market share, when a new antipsychotic adds points to the IQ instead of inches to the waistline. Even in a cost-sensitive environment, price will not trump clear clinical superiority. But for now, these companies will obliviously slash R&D, cutting very near their own jugulars, ironically strengthening the very same generic companies against whom they are struggling.
2) Biologicals! (The Musical): Having spent so much time and money trying to develop small molecules, several BP's have decided that biologicals are better. In the CNS world of course, there are some complicating factors, particularly that biologicals have a problem getting to where they need to go. The immunological issues raised by MS therapies, and the AD biological candidates in development, augur challenges that may yet make companies look back fondly at the days of small molecules.
3) Developing Countries: With First World countries having found that they are having trouble paying for, and justifying, the costs of redundant and often ineffective therapeutics, now it's time to see if we can get the developing world to buy them. After all, the tobacco industry was able to shift cigarette sales to Asia, so it should be easy to sell ineffective drugs there as well.
4) Merge, Baby, Merge: Spending $68 billion on a major acquisition is like deciding to eat all of one's meals for the next five years in one sitting: Doing so is guaranteed to wreak havoc with digestion, agility, and health. It does however, give some bankers and attorneys a reason to live.
NI's Prediction: In 2012, when the industry goes over the cliff, the next generation of CEO's, who will have replaced those fired from the present crop, will sound very much alike in their CEO Roundtable Interviews: 'We need to build our R&D capabilities both internally and via licensing, because we cannot underprice generic manufacturers'; 'We need to renew our focus on small molecule development, since CNS disorders represent a particularly large and undertreated market'; 'The three of us who are left will continue to consider merger and acquisition opportunities as they arise'.>>
NeuroInvestment
I don't want to spend too much time on this, but I don't "say/infer" something about "several others." I actually have no personal doubts about the genuineness of the viewpoint expressed by yourself, 'Haysaw', 'MarketFest', to name three. I may disagree, sometimes strenuously if I feel (perhaps too easily) provoked, but I see nothing that suggests hidden agendas. But as someone else pointed out about 'Iggs' a couple weeks ago, when a poster seems gleeful in pointing out the direst of scenarios, even as he/she claims to have an enormous stake in the outcome, there is a level of cognitive dissonance which eventually leads to the conclusion that they are either deceitfully manipulative or crazy. And I don't think the latter applies.
'Proof?' All I have is thirty years of clinical experience, some of which during the final decade involved assessing physicians who wanted to get their medical license returned, after having been caught doing something stupid or sociopathic--where looking for inconsistencies was part of the process, because many of them certainly weren't inclined to be honest in their self-disclosure. Based on that 'radar', which is certainly not guaranteed accurate, I somewhat reluctantly came to the conclusion here that there is something 'off' with this particular poster--not necessarily with a specific agenda on behalf of anyone else--there are people who simply enjoy raising havoc. I don't even care what the agenda is: I do have a problem with someone who seems to be taking a bit too much pleasure in his schadenfreude--again, I am not referring to you.
So that's my own internal metric. It may not be much, but it's all I've got.
NeuroInvestment
Mr. Blatch:
My own view is that everything you cite as reasonable content for the Board is valid. But that's not what happens on occasion, and has happened of late:
The best recent example was when I posted information from a conversation I had with the CEO of another company, where that CEO criticized Cortex for not having raised money by any means possible when possible, instead of attending to shareholder fears of dilution. Noting that there would have been a negative response from several had they done so was in my view, a statement of fact. Indeed I likely would have been among those complaining. The response from a couple of people was to accuse me of 'blaming' the shareholders and shilling for Cortex, a bizarre twisting of information processing if ever I have seen one.
I do take umbrage--and will continue to--if statements using terms like "near-criminal" are used as substitutes for reasonable skepticism and questioning.
As to speculating about what Cortex has done and is going to do--that's 90% of what is discussed on this board. There is a difference between doing that and making snarky, insincere doomsday predictions which appear to have an underlying agenda (no, I am not referring to you).
This isn't a double standard, it's simply maintaining a reasonable single standard.
NeuroInvestment
All I know is that your posts reek of dishonesty and a highly selective parsing of facts. On a day that the Dow closed well under 7000, Cortex hitting the 30's doesn't say a whole lot about your predictive prowess, or shareholder 'voting.'
NeuroInvestment
DavidAl:
<<As for the PIPE. It should have been done yesterday, last week, last month, in December.>>
Maybe, but the credit markets weren't exactly fluid and accessible November-January. I don't closely track BIO financings (Dew does, perhaps he has some data on this) but my impression is that there is a slight thawing now, in comparison to the nearly complete paralysis of December.
The question is not so much whether they should have financed in the midst of nuclear winter. In looking back at the price appreciation that occurred in anticipation of an ADHD deal and FDA go-ahead....if there was an opportunity missed, that was it. But because the possibility of nondilutive partnering money seemed high, they eschewed getting fiscal 'insurance.'
Hindsight is 20/20...I know I was not advocating doing a financing at that time.
NeuroInvestment
<<Transfer blame to shareholders...>>
That's a fairly infantile interpretation. It's not all about you. That CEO was not being complimentary, he saw it as a mistake. The concept fits with what has at times been discussed rationally on this board--the question of whether Cortex management had not financed when times were optimal, leaving them to have to do it when they are not.
My point about shareholder response was that I have no doubt that you, and some others, would have complained loudly had they done so.
And as to "another option would have been to forge an industry partnership:" If you're not going to process information, I gather your only purpose in participating here is to blame and whine. This has been discussed, it looks like you weren't paying attention.
NeuroInvestment
It's possible, but I don't think it's probable. The RD and SA interested parties only partially overlap, the former is largely a hospital product based market, the latter is almost entirely outpatient. Very different marketing forces needed.
I think your list of other factors is on-target. I would add that (I was wrong about this on RD, where assessing drug effect was much more complicated than I'd thought, this should be much more straightforward) I expect Cortex to be watching the first few trial completers very carefully. If they see a clear bifurcation of the patients (no apnea change vs. something clearcut) I would not be surprised if they were to break the blind early--if there is a possible SA deal hanging out there awaiting some POC.
BTW--an interesting aside. I had a conversation with the CEO of a successful (lots of money) biopharm company the other day. He actually brought up Cortex as an example of a company which has a good platform but had been overly concerned with not diluting shareholders, hence their current fiscal situation. His view was that Cortex should have ignored shareholder opinion and raised much more money in the past. In hindsight, one can certainly agree that would have been preferable. But at the time, few if any posters were arguing for going for as big a PIPE as possible.
NeuroInvestment
Re: the disease modification claim in general
There is a debate as to whether one can accurately parse out disease-modification statistically or not. The main issue as I understand it (which is at a very simplistic level, since my stats training long preceded the development of these models) is establishing whether the change in the slope of decline seen in a (NHSS) 'Natural history staggered start' method establishes that a drug actually changed the disease process itself, or instead delayed disability by preserving compensatory mechanisms longer. While both are clinically useful, these aren't the same--rather than actually slowing the degenerative process, the latter amplifies the intensity of 'workarounds'. In Europe, the regulatory authorities are apparently not inclined to approve a 'disease-modifying' label unless biomarkers are shown to change, they are likely to be convinced by a statistical substitute. Instead, they may allow a label of "delayed-disability." The FDA might be more easily persuaded, since it was Paul Leber who came up with an earlier version of the staggered start approach.
In Alzheimer's, no clear biomarker exists (it's not clear that amyloid load or volumetric changes are relevant/valid measures). The best biomarkers we have are the lesion analyses in MS.So there is no current way to prove disease modification in Alzheimer's.
The NHSS was developed by this Hendrix group when they were at Myriad Genetics, and hoped to use it to establish a disease-modifying claim for Flurizan....which instead failed completely.
Medivation is hoping to achieve that claim for Dimebon. The issues specific to this trial IMHO are: 1) the short followup period, skeptics can argue that 18 months total is not enough to see whether patients who received Dimebon have truly durable effects upon the slope of deterioration. 2) My longstanding questioning of the Dimebon data is that it only tested 183 Russian patients, a small number in a limited demographic sample. Pfizer apparently decided that the study itself was not tainted by local corruption, but this was still a tiny sample upon which to build Phase III and a partnership.
NeuroInvestment
Dew:
A quick count shows about 60 are discovery/preclinical, the rest have reached some type of clinical stage but have not been either commercialized or killed (though a few are suspended).
This database doesn't include quite a few Big Pharma programs that are discovery stage and have not come to light, nor the many academic lab programs that are looking for someone to license them.
NeuroInvestment
I agree with you, but unfortunately, every time there is another story about one of the Big Pharmas having mismarketed, lied, or buried data about a drug, it reinforces exactly the opposite belief system--that the FDA hasn't been tough enough. So I'd like to think Obama and/or his inner circle can see the big picture as you describe it, but the Congressional grandstanding epitomized by Charles Grassley is going to be an obstacle that will have to be overcome.
NeuroInvestment
While an interesting point, I don't think that is the case. Populations who have depression, schizophrenia, or are elderly would most likely not have optimal synaptic transmission, and thus would not run into the ceiling effect you are suggesting.
We are reinventing the wheel here. Human populations do not perform predictably on this kind of relatively soft testing (as opposed to harder lab value endpoints that don't really exist in CNS). There is a reason that everyone runs duration studies, they hope to eliminate some of variance that plagues these trials, but not always successfully.
An example--Targacept ran its own 16 week duration trial for its nicotinic agonist TC-1734, and reported remarkably robust efficacy data in a mild, AAMI population (where the upside potential would seem limited). AstraZeneca partnered, ran a much larger trial in Alzheimer's, with a three month treatment duration, and the results were negative. Interestingly, they were negative not only for TC-1734/AZD3480, but also for Aricept, which was used as an active comparator.
AZ has spent months since trying to figure out why. The drug completely washed out in schizophrenia. Now they are waiting for ADHD (!) results to figure out whether to kill the drug or not. And it's this kind of unpredictable, seemingly contradictory pattern of results which makes CNS disorders so difficult.
NeuroInvestment
I'm saying that with the heterogeneity of the AD population and their response to a drug intervention, you can't parse out what is drug response and what is placebo response cleanly--you have to let the latter dissipate. Yes, this does imply that there is not the kind of huge treatment effect from an Ampakine that would completely eclipse the placebo effect--we know that from the couple thousand individuals who have received some type of Ampakine from Cortex, Lilly, Servier, or Organon.
NeuroInvestment