It certainly sounded to me that he called the upcomming Andro for fertility trial a slam dunk.

Re FLML Coreg dates

The OP was about the flame out in 2007, so these dates certainly seam reasonable.

But I will disagree with Dew and go with the majority opinion that Coreg-CR can not sell against the generic Coreg-IR at a fraction of the price.

Did FLML (or the patent holder) file suit against the challanger? If not, the the generic -CR will be on market in less than a year.

Dew, on the denominator

I did see those numbers. One guess though is that those were the total number of patients at the end of the year, not the start.

If so, this would have yeilded larger % resistant number than the true KM (which would have had a larger at-risk number at most all points). The effect would have been big enough to explain the descrepancy.

Seams stupid, but who knows. It is just a PR.

I think my other guess that it could be changed data over time seams unlikely, as the Y5 data really drives this.

"Could you please explain your post, in plain English, to a non-stat guy?"

I am not certain if you mean the whole post or the quip at the end, so I will address both.

1) The no serious discussion quip.

Many posts ago another poster questioned why we had little serious discussion on this board. I decided to try and get things going with an admittedly negative post. The response from a board leader was a personal slam as opposed to any effort to debate.

2) Real issues.

IDMI might be a good investment, and MTP-PE might be a good drug. What I posted was that the trial used to support the NDA last year was a dismal failure. The FDA tore it to shreads back and forth. This is NOT to say the drug failed, just that the trial failed because of it's deisgn.

Re: 5Y baraclude data

If this is followup data as time goes by, would we not also expect more data points in the earlier years that could change those nunbers?

I also would expect a difference between the actuall KM curve and calcualtions done by collapsing the time interval to 1 year (but this should go the opposite direction unless we don't really know what the at-risk number was in the PR).

OK, I am bashing w/o DD

Quotes per FDA :

http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4301b1-02-FDA-redacted.pdf

The experimental arm issue:

"INT 0133 was a multi-center randomized open label study. Two therapy-related experimental questions were investigated in this study.

1. A comparison of two chemotherapeutic regimens: standard arm (Regimen A: high-dose methotrexate, cisplatin, and doxorubicin) and an experimental arm (Regimen B: a modification of the standard arm with the addition of ifosfamide).

2. The contribution of MTP-PE given in combination with the chemotherapeutic regimens - Regimen A with or without MTP-PE and Regimen B with or without MTP-PE."

"There are three main issues regarding the DFS results:

1) The Applicant’s result is sensitive to changes based on FDA review of CRFs, patient’s eligibility and investigator’s additional follow-up data;

2) The Applicant’s result is driven by an experimental arm which performs worse than the control arm; and ..."

"Applicant’s result is driven by an experimental regimen performing worse than the control regimen"

[The experimental arm refers to the arm with ifosamide+SOC. Look at the KM curve on page 21. The Green and Blue lines show PFS data w/o ifosamide. They are IDENTICAL]

You: "Frequently trials do not go as planned and require revised statistical procedures and often more data gathering. IDMI had to do the latter"

Complete BS. So you are a stat guy? Then you should understand you can't just go changing the plan and gathering data until you hit stat sig. See for example DNDN where the FDA did not allow them to correct a simple clerical error in the data set. And here you want to just keep adding data to the post hoc (per FDA) OS analysis (after all agree the primamry endpoint failed).

I completely understand why there is no serious discussion on this board.

"Why has the discussion not moved signifigantly to this board? "

OK, I will take a try.

Junoven by any name has NO chance of being approved by the FDA based on the new data (argument below). To present an "investment thesis" in the stock requires an argument that acknowledges this fact. If anybody would like to procead on this I am all ears.

Does the remaining pipeline justify a buy?
What is the EU story?
Can they possible perform another trial on a surragte endpoint?

To be honest, I am not in IDMI either way. If somebrody has a reasonable argument to be in (that doesn't just ignore the Juno trial data issue) then I will happily debate. I do like to invest in somewhat busted biotechs.


----

When IDMI took Junaven before the FDA, they got shot down on several serious issues. In order:

. The trial had no defined stat plan or endpoint
. Juno only showed a benifit when another UNAPROVED drug was used concurrently. W/o the unapproved drug, Juna didn't show a benifit.
. The database was seriously flawed.

Getting a drug aproved on a single trial requires quality data. This trial was the complete opposite. There is NO chance that adding a few UNBLINDED datapoints will change the real issue.

One other post on Assensio.

The guy does have a good track record of finding scam companies, but certainly not perfect.

More importantly, I would consider his claims against ZONA/RPRX to be bogus and deceitfull.

1) He used the term "oral deliverly" to confuse the patent issue that was really about the digested drug vs a directly absorded form (in this case "melts in your mouth"). Upon reading his version I thought the issue was clear cut. In actuality it is a close call and if I was on a jury would likely support RPRX on patent applicability (and I dispise the patent system)

2) His other call on the immuMAX(?) patent being rejected implied it was fraudulent. This is crap. Most patents are initially rejected.

I doubt we will ever know what truelly went wrong here. But I would close the door on it with "shit happens".

"The vultures and sharks and eels are circling"

Well, I see the sharks and eels.

I just wish we could get close enough to being above water that I could see the vultures

RE: ZONA and the Vasomax pattents.

Here's probably the best definitive answer on all this

http://securities.stanford.edu/1007/ZONA98/2003613_r02o_9800693.pdf

Here's the Reders Digest version -

Background:

Zonagen had claimed that Vasomax was covered by a patent (Zorgniotti) they had rights to. Assensio (a short tout) called BS on this. After the blow-up, law suits were of course filed. The last claim was this claim that the PR of pattent coverage was fraud.

Zorniotti pattent and Vasomax:

The Z pattent covered the use of phentolamine delivered through muccosol tissue (oral, nasal, rectal) as a treatment for MED. In particular, it teaches the advantage of this over a digested form because of liver action. Vasomax is a fast dissolving tablet of phentolamine.

The Judgement:

The court granted summary judgement in favor of ZONA based on the fact that the defendends could not establish the share price was elevated by the pattent claim.

In discussing the pattent claim the court indicated that
1. The Z pattent did not cover Vasolmax
2. ZONA may or may not have acted with intend to decieve here (would have to be decided by jury).

My View:

It certainly made sence for ZONA to buy the Z pattent in order to protect Vasomax. It's the way pattent biz works today, get whatever you can and let the courts decide.

I woud certainly give RPRZ management the benifit of doubt here.

Way Way OT:

Does anybody see something slightly perverse in administering a drug rectally for MED?

Re: Kelly Criterion

In 21 Kelly betting (risk adverse bettting, generalized Kelly betting) actually does come into play for serious players. The proportion of your stack you wager on a hand will vary with the expectency/sd. This can be calculated for any deck composition (as measuered by the count).

It doesn't apply precisly for many reasons, but aproximations do. It is an eye opener how little you must bet to avoid a serious risk-of-ruin.

It will not apply to backgammon because N is way to low, and there will be no solid numbers to back it up. It does tell you the obvious though, that you can afford to bet more against weaker oponents

In biotec I can see one obvious place where the concept (but not the math) applies.

Suppose bioteck ABC is a certain 90% to get it's drug approved, and if so the stock will rise 122% (else go bust). While XZY is 10% to get the FDA not, and will rise 1900% (else go bust).

Both stocks are an expected double, but you clearly would not buy as much XZY as ABC. So, ABC allows are higher total dollar return.

Of course, you also can use options if available to adjust the risk.

I believe the EU issue was that they didn't run a trial against Curosurf which is the EU SOC or some such.

If such, they would still have potential EMEA issues, but this wouldn't effect FDA.

As to FDA, we really do not know if the CMC issues are resolved. Must wait and see.

OK, y3maxx. Try and read.

Akas was asking "what the value of a SPA is". I tossed out a comment that it might not mean as much as it should if you can't trust the company anyway because of cases such as Statraplatin.

RPRX does not have a SPA.

It should be not difficult to understand that I can not be accusing RPRX of having a fradulent SPA when (as I admit) they don't have one.

WHAT IS SO COMPLICATED FOR YOU GUYS? I NEVER IN ANYWAY IMPLIED RPRX WAS EVEN MIDLY LINKED TO A FRAUDULANT SPA.

OT - RE: "Did you actually use the word fraud with regard to the SPA?"

I am not by far the first person to use this (or worse) language with respect to the Satraplatin SPA issue. You might try an visit a SPPI board to see what they thought when this issue broke open. Even the mild mannered Clark had harsh words.

I will give SPPI some benifit of the doubt here, but not GPCB.

In case you do not know the story, when Satraplatin hit it's primamry endpoint (PFS for PC) most thought aproval was a lock because the trial had SPA. Turns out, GPCB ignored the SPA and used an endpoint the FDA strongly disagreed with.

If you know more details of this than me, feel free to speek up.

NOTE! I called this OT because I nowhere said or implied this has anything to do with RPRX. This was in response to akas's post about what a SPA is worth.

RPRX does not have a SPA because they are trying to save a few months time. We all can have an opinion of this, but fraud is not in the picture.

Akas., sorry for missing your post. With all the fighting gone on here I thought you meant this as a "prove it or shut up" post.

Back on your point, I doubt it will be easy to get data on how SPAs help aproval percentage. SPAs are kind of new, so you probably need to wait a few years.

To me, the big advatage of a SPA is that I don't need to spend much time thinking about the trial design. If it is good enough for the FDA, I'm happy. I then can focus more on the drug (and I have never argued that prollex looks anything other than what it seams), the market and the company.

Of course a SPA doesn't protect you from outright fraud. See Satroplatin (and I will use the fraud word in that case).

akasid. , re terminology issue.

Kind of funny you slam me for this post when I was making a positive statement.

For history, 2 months ago I questioned the terminology "registrational quality trials" used in a RPRX PR.

My question was meerly that the phrase COULD be "weasle language" to make it sound like the compnay states the trial was registrational, when the actual statement does not imply that.

Some posters replied that w/o a SPA, this language issue was meaningless. Yet that didn't change my position that a compnany shouldn't use non-statements when it can be clear.

In the CC, the replaced the language with "registrational P3 pvitol trial". I acknowledged this in a positive sence.

But I guess you will just lash out without reading.

He also called Androxal for fertility in hypotestosterone (?) men a slam dunk.

I wasn't even positive what he precisly meant here, as the voice kind of drifted out right then. Did he mean efficiacy data, or the indication as a whole?

Well, they did address one of my minor points about the terminology of the anemia trials, explicitly stating it is pivital (not registration quality). No need for anybody to remind me that this is a near meangless distinction without a SPA.

OT: Bear Sterns at $5.9?

This is going to be bad fight. The market (not just joe idiot) is saying the $2 is not going to happen.

Combined with lawsuits and public outrage over the Fed $30B support for the deal, we will have some good entertainment here for a year or so.

Re: "It is so obvious that the hedge funds control this stock"

Well, I guess I am just not too sharp then. Could you point to some factual evidence that makes this obvious?

Be warned, before you reply. I will repost your evidence substituting singing chipmonks for hedge funds.

I admit I did not ask a Q at the CC, was not even there,

0:30 AM local time is a bit difficult, but more importantly I never had the slightest clue I could really ask a Q on a CC after identifying myself as an individual investor.

Perhapse next quarter I will try such, certainly I could believe I could post a more intelligent question than do some others on these calls. Would be fun.

Of course, I suspect reality is I will not be given a floor.

Re: "Would you still say that the 2% difference was significant?"

Point well taken.

Boy, my nuts certainly hurt while sitting on this fence

re: noise

I agree that 2% is not noise.

But the big power calc question is not if DNDN used to large a HR, but clark's question about applying a constant risk model at all here (in the power calc analysis).

Many of the now censored 50? events will occur in the "meat" of the curve where you both have good seperation and sufficient events. None would have occured in the early months nbefore seperation.

I would not be surprised if one had a "real" curve and did a sim on it, they lost more power because of this than the 2%.

Regardless,

1) I do hope it (the final) hits a solid p value.
2) Management is not very clear what is going on and why.

Re: Androxal and the EU

The issue with Androxal is or course the FDA decision to not allow T replacement as an endpoint.

I really call BS on the FDA here. If T replacement is an efficiency endpoint for any drug, then it should always be such. Yes, they could make the argument for stricter safety testing, but that is a seperate issue.

Do we have a rulling (or gut feeling) on the EMEA position here? If they would go for T replacement then the drug should immediately be licensed ex-US. I do think it has more value than some of the nay-sayers imply.

[[[ funny edit, I just corrected the last sentance to add "imply". I could imagine the assults I would have taken if gone uncorrected ]]]

I spel justt fian, thank yu

Seriously, I would say:

1) How did you ever come to the impression that I am not aware that my typing skills just plain suck (and my spelling is poor)? Do you just make stuff up in your mind?

2) I would certainly consider that typos, spelling and such are probably less significant that not being able to understand the concepts involved in a discussion, or know common background facts. Did you REALLY not know what ocean I meant when I said Artic.

"o/t: Didn't you mean 4 oceans/seas? "

No, we were talking oceans only, no seas. I certainly was talking about the Artic ocean.

[I have heard some call the artic a sea which confuses the issue]

RE: The list goes on and on. (ignrance)

I cam across the following on some long lost MB with a EU slant.

"30% of US students counld not identify the TWO oceans that the US has a coastline on". As they continued to deride the US edutcation system based on this, I had to point out that there where of course 3 oceans, so it is a tad tough.

To make it even worse, one responder said the question obviously did not mean to include islands and territories such as Hawaihi, but only the continental US.

Humour aside, I am stunned when I sit in a bar that has one of those trivial games going on. One the question gets off pop culture or sports, half the field seams stumped by the easiest questions.

"Q: Does the Earth revolve around the sun or does the sun revolve around the Earth?"

The answer is either YES or NO.

If you are talking wrt general relativety you can set your frame of refrerence however you like, and either can be said be to revolve about the other (or any other object)

If you are talking clasically, they both revolve around the solar system center of gravity, which is not the center of the sun.

So I guess we must now "dumb down" are tests for ignorance

The evils of percent of percent.

I would be more concerned with a move from 70 to 65 than the 90 to 88 change.

I would also be MUCH more concerned why management always knew the orriginal interrum was probably hopeless, but maintained otherwise publicly.

"what the hell is the integrated hazard ratio"?

I think it came from Brown vs. Board of Education

Damn that Daylight Savings Time

Anybody check the I-Village board for DNDN? Should be interesting.

DNDN's statistical model changed when they got financing in the summer of '07

Before then the model was to take a moonshot on the interum working, else suffer major dillution while waiting. Now that they got more cash, the decided that hey could afford to wait for the final, so reduced the interum alpha.

None of this takes astute staticians to figure out. What's difficult is the tradeoffs involving how important results are in a particular time window.

This was a biz decision.

BTW, did the FDA tighten the screws on alpha any to make up for this game? We will never know.

RE: Injectafer safety issues

Somebody sharper (and with more time than me at this second) might dig deeper, but here's my understanding.

Injectafer is a method of treating anemia by iron suplementation (it doesn't reduce the bleeding). Whatever the safety concern is could not even concievable apply to Prolex.

Here's the ranscript, alas no nice briefeing materials.

http://www.fda.gov/ohrms/dockets/ac/08/transcripts/2008-4337t1-part2.pdf

Clark shot down that logic fairly hard over on the DNDN board.

The key is that the probability of success at the final has DECREASED.

The reason is this. The final look has less events. In THEORY this cancels the increased alpha. So the final should have the same chance of success.

But THEORY here uses a constant risk assumption. Not valid with Provenge. The Provenge curves show a late seperation. This means that late events help provenge more than early events.

Thus, in reality the power of the final has been reduced.

I really doubt you need to name names

Re: DNDN's SPA change IHUB response

Actually, there have been 3 replies to DNDN's SPA change while in trial (dewd on the values mb, and iwfal and myself on DNDN). All posts were negative.

I had the most neutral post, saying it was just money driven. Iwfal slammed the stat side along with mgmt while agreeing that the change was likely cash driven. Dew just said management is so f** that there is no point evaluating the change.

If somebody posts a positive, that would could start a debate. But you can't argue with nobody.

DNDN realized they were spending to much alpha on the interum, so they took it away and gave it to the final.

With the extra alpha in the final, they could reduce events w/o effecting power.

Then they push back the interum to give it more events (since it would have had no chance with the reduced alpha otherwise).

One might ask "What changed"?

My guess is that it was as much a financial "time to live" decision as a pure trial design issue. The only question I would have is if they shuld have just assigned no alpha to the interum (though maybe they effectively have done so).

BTW, I am not being particularly critical of RPRX (just questioning). And I do kind of follow dewo's view on the drug proper (I believe he is very honest wrt the value of a drug that delivers the clinical benifit Prol. is looking at).

I just sometimes get tired of the happy face stuff.

Sounds just like Tony Snow interviewing Bush.

How about some real questions?

Why 15 patients in the palceboe arms of the 4 trials, especially when you know many will drop out?

Why no SPA?

The FDA does not like companies to use higher dosages than have been shown effective. For anemmia, why is the 15mg dose not in the P3?

What are the endpoints? In particular the company states the trials are 2.5X bigger than the P2s. So, this implies a composite endpoint of both arms treatment arms, or a P reduction. If composite, isn't that a danger in the fibr. trial? If a P reduction, what?


I know all these issues were beaten to death, so no need to ask. Just present the softballs.

Doc has already made clear that there is no reason to discuss the trial size issue with management.

So why question him on this?

OK, what am I missing here?

The anemia study is up against a placeboe, which makes it virtually open lable because of amenorhia.

So you want to have somebody go around and monitor the patients and insure compliance?

Perhapse they can try and guess anemmia before arguing with the patient to stay in the trial?

Or perhapse they should look at the surveys and decide if the placeboe arm patients shoud stay in the trial?

And you guys see no issue here?

"Why wouldn't an increase in progression free survival result in an increase in time until death?"

The best answer is that there are cases where trials don't show the corrolation.

One easy guess is that the harm done by a particular chemo might be just as detrimental to survival as the increased tumor burden w/o the drug.

BTW, I do see the orriginal point of the quote that many patients will misunderstand PFS. But I hope they don't start "dumbing it down" so much that an intelligent patient doesn't get accurate information.