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Wall--
May a lawyer weigh in? If hearings are held--and I think there's a good chance they will be, because Congressmen love a scandal to grandstand about, especially in the name of helping dying cancer victims--I would fully expect that the investigation will very quickly move from COI's to Pazdur's role in stalling Provenge in the interest of his turf war. The situation is very far from simple having COI's and not disclosing them. The focus is also going to be on the extraordinary measures taken--not just voting "no" and speaking out against the treatment--but sending letters to the FDA after the AC, such letters being not authored by the sender (were they authored by a hedge fund, by Pazdur?, by someone ordered to do so by Pazdur or a hedge fund??--all these issues will be fair game), that the letters were inaccurate and self-contradictory, leaking the letters to the Cancer Letter so that they would become public, any behind the scene threats by Pazdur to have an anti-Provenge demonstration at the Orbec panel if Provenge was approved (as David Miller has speculated), who was behind the question posed at the AC being more stringent than the law's requirement. I probably have even left out some juicy points--but the salient fact is this: there are many whose careers could be on the line--Pazdur, Scher, Hussain, Fleming--and who even could face serious jail time. Where is Sam Waksal right now?? Where was Martha Stewart for over a year??
More important to us DNDN investors (I'm back at 80,000 shares) is--where is Erbitux now?? IF serious misconduct changed the FDA decision from "yes" to "wait for more data" Congress definitely has the power to set it right--as does the fear of lost jobs and prison terms. Until now the cockroaches Scher, Hussain, and Pazdur have been able to get their way behind the scenes in the dark--when the light comes on, roaches scurry to save their skins and the lights are coming on. I'd bet anything Scher and Hussain have already contacted experienced criminal attorneys (they're crazy or naive if they haven't) and that Pazdur is calling in all his chits to try to cover his ass even as we speak.
Lawler is a joke--his column is routinely filled with incorrect facts and dull opinions. He doesn't even have his college degree yet--he's a college student earning extra cash by mentioning DNDN whenever possible for MF to get as many hits as possible. Feuerstein used to be a little better, but he too does little detailed research and lately has lost his objectivity after letting negative emails from dendreonites get under his (thin) skin. Now he reflexively dismisses any news suggesting good things for Dendreon. His column has become worthless--although he too mentions DNDN at every opportunity to get hits. (Of course once Provenge is approved, he'll crow about his post-AC call that approval was likely--he's got his bases covered--can't go wrong by predicting success and failure, you're sure to be right).
IF hearings are held, it is definitely a big deal and could result in conditional approval for Provenge conditioned on completion of 9902b.
Interested parties can help it happen by calling, emailing or writing the panel Chairman to back up the call for hearings.
I can personally and publically attest that he is a douchebag--shortly after he first changed his call on DNDN from a "buy" with a target of 28 to a "sell" with a target of 5 someone on the then not totally messed up Yahoo MB posted his phone number. I called and talked to him. This was when management had announced that 9901 was stat sig for survival, but the actual data had not yet been made public and Mr. Pretend-doctor was trumpeting that management was actually lying about the data. He told "the numbers don't look good" for 9901. When I asked if he had any numbers other than those already made public he said "No". When I asked him to clarify--he declined, saying he had so many phone calls that day he couldn't talk anymore.
Anyone who has followed the story knows he has been consistent in only one thing--trashing Dendreon. His "reasons" for doing so have been as fluid as water, and as Wall points out, have been wrong 90% of the time. He's the proverbial blind squirrel endlessly crowing about the nut he found.
Thoughts on strategies to profit from likely events?
The judge in the Caretolive suit yesterday sent a clear message in denying discovery until he hears the Motion to Dismiss. As an attorney I believe it's close to 100% he will grant the motion. Even if the allegations of politics at the FDA are true, those who had the decisionmaking power as to Provenge were still within their discretion to ask for more data. There's little chance he'll find they acted maliciously or outside their authority. Opinions on whether another drop is likely once the suit is thrown out? Or will that likelihood already be priced in?
Opinions as to likely reaction of share price if interim is not "successful"? What is "success" for the interim? Minimum p value for interim that would still suggest final p value may be stat sig?
I personally plan to add to an established core stake (50,000 shares) if the pps sees the 6's after the suit is dismissed and to hang on pending the interim. I'd probably go 100,000 shares on the chance the interim succeeds.
If it fails, but in a range that the study continues and management still pipes optimism for final results and the shares hit pre-AC levels I will probably again go all in to await the final. I believe Provenge works and that ultimately Impact will show it.
What do you all plan??
I keep hearing conflicting things about the likelihood/chance that the interim look will succeed. Anyone care to share a line of reasoning based on the Petrylak findings regarding the combined effect of Taxotere and Provenge on survival? I have heard it argued that the "sicker patients" among the newest enrollees will make the interim unlikely to succeed--but I have also heard that the awareness that Provenge and Tax together may dramatically improve survival might increase use of the combo and help the interim. Any opinions out there?
How do you get that 30%? If Provenge produced a benefit across all Gleason scores--which it did in 9901, then on what basis do you worry that the sicker patients will skew the curve? Isn't it true that sicker or healthier for each class of patient the average survival advantage was 4.5 months?
Can anyone answer this: I know the interim look for Provenge is triggered by a certain number of death events and we know that Gold has said the number is more than were in the pooled results of 9901 and 9902a. The primary endpoint is overall survival. I have also heard that a Cox regression analysis is prespecified. My question is--is the interim look also to be subjected to the Cox analysis and is the Cox analysis to be that which maximized the p value in 9901? Which p-value will the FDA be looking at, the raw p-value or the Cox adjusted p-value to determine if the interim provides sufficient support for Provenge's efficacy to justify approval??
If the pooled results were stat sig at p=.011 and the interim will have even more death events and be subjected to a prespecified Cox analysis, why is everyone so skeptical that the interim will be sufficient for approval?
Lastly, I have to say as an attorney that I have little hope that the Care to live suit will have any luck. My experiences suggest that federal judges bend over backward to protect federal agencies and will even be hostile to the strident (although I believe accurate) allegations of the complaint. That said, the dismissal of the suit could prove to be a buying opportunity for those who believe Provenge works--price might dip as those hopeful of a good outcome to the suit bail out. Anyone know when or if a hearing is scheduled on the motion to dismiss??
Copied from Ivillage:
Here's a copy of the letter I just emailed to the editor and copied to Stein:
To the Editor--
It's great you are covering the FDA's refusal to approve Provenge, the first of its kind immunotherapy vaccine for late stage prostate cancer. It is the last hope for many men dying of this widespread disease and has been shown in two phase III trials to meaningfully extend lives with practically no side effects--unlike Taxotere, the only other approved treatment, which half of men reject because of its harsh side effect profile (which can include death).
I only wish your article were more on the lines of an investigative piece, and did not read like the "balanced" he-said, she-said journalism that sadly passes for good reporting in most other papers.
The fact is the FDA expert panel voted unanimously that Provenge is safe--a vote of 17-0--and 13-4 that there is substantial evidence of its efficacy.
It is also a fact that two of the dissenting voters, Drs. Scher and Hussain, were on the panel pursuant to conflict of interest waivers because they both conduct research for companies with products competing with Provenge (including Taxotere--mentioned above). In fact barely two months after Provenge's rejection by the FDA, Novacea, a company with a different competing treatment for prostate cancer whose lead investigator is Dr. Scher, announced a multimillion dollar partnership with Schering-Plough, to seek approval for and market the competing drug. Dr. Scher was very quiet about this obvious conflict--which one would have expected would disqualify him from making recommendations about Provenge--as he instead actively lobbied against Provenge. Novacea's share price doubled on the news. Dr. Scher's conflict of interest waiver on file with the FDA discloses ownership of significant shares of Novacea.
In light of these facts your readers may have had somewhat less sympathy for the poor doctor, harassed by dying men who wanted Provenge.
It is also unfair to dredge up the Vioxx and Avandia controversies in a discussion of the delay of Provenge approval. First, as above, the panel voted unanimously that Provenge is safe--which included the votes of Drs. Scher and Hussain. Second, standards of safety are very different--and should be--for drugs that are intended as treatments of last resort for terminal illnesses and those that are intended for chronic ailments in the general public.
Men who are dying should be allowed to make their own choices regarding whether they wish to risk any known side effects of a drug that has been shown to extend lives. In fact Provenge's only known side effects are mild flu like symptoms for a couple of days.
The FDA statisticians testified that there was only a 1 in 40 chance that the trial results showing Provenge's effectiveness resulted from random chance. A 97.5% chance of effectiveness seems like a pretty good risk to take for dying men. How exactly is the FDA serving these men's interests by denying them this chance to live?
I hope you will follow up with a more in depth piece.
Saul Kerpelman
Is it possible Gold's sale cuts the other way? Can't they argue that he must have believed the 483 issues were minor and could be handled post-approval by agreement--otherwise wouldn't he have had to have been afraid of going to prison ala Sam Waksal if he really was trading on what he knew to be material inside info?
I'm not arguing for that--just playing devil's advocate for the other side while I consider whether to join or not. Is there an easy answer?
With respect to 9902a I think all oldtimers also recall the coy game Gold played with respect to 9902a data--namely repeatedly assuring us the results were "similar" and once or twice "very similar" to 9901--before the exact numbers were made public. Last I checked a p value of .331 is not "very similar" to a p value of .01. Shares took a giant hit when the truth came out, if memory serves. Not much credibility with me.
But Ranch--what do you say to David Miller's insistence that the class action is going to be tossed based on precedent of much more blatantly egregious failures to reveal 483's being dismissed with prejudice? I am still considering whether to join the class.
Wall--
I agree. Feuerstein is really not a careful reporter--he's more like a columnist--expressing his opinions and not always caring or analyzing carefully whether his opinions add up. Shoots from the hip. Reports his impressions. I was irritated by his statement that "The FDA examined Provenge's data and found it lacking". Talk about not being a reporter! That crystalizes the guy in a nutshell--ignore the politics at the FDA, ignore the mindless adherence to outdated endpoint purity, ignore the extra conflicts of interest revealed for Scher, ignore that the FDA truly pissed on its mandate to thoughtfully perform a cost/benefit analysis of Provenge with the idea in mind that terminal patients are desperate for treatment... I could go on, but you get the idea. He's typical of just about everyone at The Street.com--superficial lightweights flying by the seat of their pants. The only problem is those guys often move the market and are a factor in overall market perceptions. I don't usually do such a thing, but I sent him a reasoned email pointing out his sloppiness.
What exactly did Gold say about the requirements for approval at the interim analysis? I know it is best to assume that the FDA is going to stick to a requirement of statistical significance, but no one has explicitly said that have they? Under the FDA's rules the company has one stat sig study--the real issue that made panel members worry was not explicitly that 9902a was not stat sig, but that it was so far from stat sig (p=.331) and the average times to death of everyone in the study was so different from 9901 that they questioned whether it was in fact "supportive" of efficacy as shown by 9901. All they really could say was that 9902a showed a "trend" toward efficacy. I really think that if 9902a had been close to stat sig (say .1 or better) that the ODAC people would not have had enough ammo to delay approval given the safety and the dire need for treatments. If that's true (and I welcome debate about why it's not) I think even if the interim for 9902b is not stat sig, but shows a clear trend suggesting that the final analysis will be stat sig there may be enough pressure on the FDA as a result of the past months' fiasco of non-approval that they may approve with final analysis as a post marketing commitment. Any opinions on that?
As for now I am out altogether, with the expectation that the stock is going to drift downward for the next year or so (maybe more--seems like they just can't get 9902b fully enrolled quickly--now they promise full "by the end of the year") as people give up hope of quick approval without the interim. If you go look at Provengenow website description of meeting with Von E it seems clear the FDA is not going to budge without more data. As this becomes obvious to all I think I'll be able to get back in at a price close to prepanel. I think for sure it's going to the 5's and probably the 4's. There will probably be a spike when they announce (if they announce) full enrollment.
I still believe Provenge works and I intend to put a couple million dollars behind that belief when the time is right--but it looks like that's not going to be for quite a while.
What do you all think?
Wall and others--
Can you statistics knowledgeable guys answer one for me?
As I understand the current situation with the interim analysis of Provenge the interim will occur when there are 180 deaths in the study. As Gold has recently emphasized in both the CC and the presentation at the conference this is greater than the number of deaths in the pooled 9901 and 9902a sample. The pooled sample turned out to have a p value of .01 did it not (maybe it was .011?)? And also the interim has prespecified that the same Cox regression analysis will be performed as that which resulted in a corrected p value for the pooled data of .002. I know there are differences in the patient populations based on the previous tinkering with the study--first Gleason scores less than 7 based on earlier inkling that that group did best in 9901, then amended to include all Gleason scores and "minimal symptoms"--but again Gold has said that an analysis of the populations finds them to be "similar" for study purposes. I also know that "most interim analyses do not attain statistical significance" as has been quoted ad nauseum in the press when discussing the interim.
My question is this--If we have drunk the Kool aid and really believe Provenge works as the explanation for the results of 9901 and pooled data of 9901 and 9902a, why should we not believe that the interim--with more patients and more death events than the pooled groups--will be stat sig--and even gloriously stat sig after Cox? Am I missing something? Do we need to wait for 3 year survival to expect the best possible results? Is there something about "curve separation" (which has never been explained to me by the way and I don't really understand--I'd appreciate an explanation)?
Please enlighten me, if you can. Seems like if there are 180 deaths--and again the vast majority are placebo guys, the interim should look as good as the pooled data did.
Congressional action is the only hope. Here's a repost of my Ivillage post:
Write or call your Congressman
Excellent point made in newsletter today that the only thing that's going to get the FDA to reconsider is pressure from Congress to do so. All the posts about billboards, etc. are wasted effort. The FDA is a bunch of arrogant bureaucratic bastards who can't be shamed--because they think they are better than you are, and that their turf wars are more important than patients' lives.
The FDA cares about funding and Congress controls their funding. If a prominent Congressperson who sits on the committee that controls FDA funding were to announce hearings on the politics behind the rejection of Provenge for dying cancer patients--that is the only hope for an earlier review than the interim analysis in 2009.
It is CLEAR that the rejection was based on politics within the FDA with CDER and ODAC battling CBER for control of cancer treatments, NOT on medicine.
There are people in Congress who care about such things.
Anyone here care to research and post the names, addresses, phone numbers of the key Congress people who supervise/fund the FDA?
That's where we need to immediately organize and exert our efforts before this becomes yesterday's news. The Prostate Cancer advocacy groups need to get a Congressional hearing or it's wait till 2009 or later and thousands of guys die.
I just watched the video on the website and it's very good. In about a minute explains very clearly how Antigen presenting cells that are activated teach T cells which cells to go and kill. Very nice.
Gotta hope that they have some good news indications from the FDA that are motivating getting this website operational. It is blatantly obvious that as soon as approval comes there will be an additional video explaining how the Provenge process takes the cancer patient's Antigen presenting cells, activates them against the target cancer's antigens, and then returns them to the body to start killing cancer cells.
No one can say if this constitutes just getting ready or if they know what is coming based on discussions of what needs to happen with 9902b and they are preparing for instant action on marketing when the formal word comes. On balance it doesn't seem that likely they'd be making the website operational right now unless they knew good news was coming soon.
Screw Clark for sure! At least we're out of the world of having to deal with that incompetent boob. I know it's off topic, but it really is a pity the way Icos turned out--there was so much potential there... Just shows how a greedy incompetent manager can ruin a promising company.
If things play out well from here Dendreon should allow us to forget that misadventure forever.
Yet another clue posted today. Check out the slide show of CBER at the World Vaccine Congress presented by the head of CBER--oh, and yes, he's the same doctor who changed the briefing question at the Dendreon panel hearing to ask about "substantial evidence of efficacy". The presentation brags about how many new biologics are being approved so that at least in CBER the FDA is a Bridge, not a Barrier to new treatments. There's even a hokey slide showing new technology on one side and drugs available to the public on the other with an actual picture of a bridge in between. Posted on the FDA What's New website this morning:
http://www.fda.gov/cber/summaries/advame...
They are definitely ramping up for approval of Provenge.
Now Motley Fool agrees; Kipplinger's agrees
David Miller's response to Scher's letter just destroys Scher's arguments.
Provenge is getting approved--it's only a question of when.
No. After HealthCor bailed out on dissenters' rights I just took the 34 and moved on. There was too much risk that a judge might find fair value was less than 34. I had about an 8% loss on my Icos shares. More than made up for by Dendreon--my cost basis is 8 and change. I hope I can hold on to that--could lose the paper gain if no approval--but I believe there will be approval with the condition that 9902b be completed. I'm all in for my investment of 2.5 mil.
Did you notice on the CBER website at the FDA--(What's new)--they posted today a final version of new procedures for post marketing studies to which a company commits after receiving contingent approval?
Hmmm...coincidence or dotting the "i's" and crossing the "t's" before Provenge is given approval contingent upon a commitment to finish and report results of 9902b?
Time will tell, but my sense from the hearing was definitely that the sentiment of the panel--Dr. Mule in particular--and also of Dr. Witten--was to approve immediately so that dying patients could receive the treatment, but with a promise to complete the larger study and to try to enroll more minorities.
At least today's posting sends a message that someone at the FDA has the idea of post marketing studies after approval on their front burner.
Here's the link:
http://www.fda.gov/cber/regsopp/8413.htm
I'm still long my 300,000 shares, and hoping the above scenario plays out--in which case I believe we will see the 40's and higher.
I know months ago it might have seemed like the usual "we're the next Amgen" stuff one reads on MBs every day, but with approval does indeed come proof of concept for the cassette technology. Once there is an actual marketed product and revenue and a multiple of earnings and there comes to be wide knowledge of the rich pipeline that the technology represents for multiple cancers--it is very possible that Dndn could become a biotech leader and see its pps eventually top 100 and higher.
Of course there are many posssible bumps in the road--as always--but it is no longer message board fluff to say that Dendreon has the potential to be the next Amgen.
The first step has been taken.
At first I was reading your commentary, but then I couldn't stand it anymore (with eagle's panic) and sprung for the 150 to watch the webcast. I went to work and missed the middle part, but got home just in time for the vote. I almost fainted with orgiastic delight when Dr. Mule suggested that the question was worded to require more than the legal standard and the FDA doc actually said he was right and the correct legal standard was substantial evidence of efficacy (I'm a lawyer, so that was sweet)--and as the yes's started pouring out... I actually did the Rocky dance after 13-4. Hope you were very long. About a year ago I met with a potential Financial advisor and he said "Are you crazy? Why do you have 20% of your portfolio in this speculative biotech??" I didn't hire the guy. No balls. You got 'em in spades, brother.
I have a son at film school in L.A.--maybe I can take you to lunch sometime. Email me at saul_kerpelman@yahoo.com
Walldiver--
Hope you remember me from the Icos Board. That didn't turn out as planned, but it did lead me to this--I still remember the day a couple years ago you posted on the Icos board "Hey, you guys might want to check out Dendreon".
I did and eventually (averaging down--drat it) accumulated 300,000 shares (last 100,000 at 4.60-4.04 last two weeks).
Sooooo--only appropriate to give you a big public thank you and also an acknowledgement of your fantastic leadership on this Board, your wide knowledge of the sector and the science, and of Dendreon in particular.
You are a great guy.
Saul
The panel didn't change the wording. Dr. Witten, who was the FDA representative at the meeting, saw that the first panel members asked to vote were having trouble with the question as worded in the briefing documents--"Has the efficacy of provenge been established?". The first 2 voters said that to them "established" meant with 100% certainty as they understood that term as doctors and scientists. Dr. Mule then asked whether that was a higher standard than the law required--and then Dr. Witten said that what the FDA wanted the panel to answer was whether the company had offered substantial evidence of the drug's efficacy--which she said was what the FDA needed to determine under the law.
Thus the FDA--in the person of its representative, Dr. Witten--changed the question.
With the newly clarified question to answer only the ODAC representatives on the panel had any trouble voting yes.
All 13 yes votes were enthusiastic that there was in fact substantial evidence of efficacy.
I believe Provenge will be approved with a requirement that 9902b be completed and reported.