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Well, I'll take that as good news then. So Dew, let's pretend you're an exuberant DNDN fan...who do you think would be a good fit to partner for Provenge in the ROW, if it gets approval in the US?
BTW, on Squawk Box just now, did you see this? Becky was asking a marketing question about the Reese's candies, but misspoke...the result being a cross between Reese's Pieces and Reese's Peanut Butter...LOL...I've never heard of Reese's Pen*s, I wonder how much they can sell it for?
Joe K and Carl Q could barely speak they were laughing so hard
Hilarious new INGN article...lmao
http://biz.yahoo.com/seekingalpha/070312/29182_id.html?.v=1
SeekingAlpha
Why Introgen is a Terminal Case
Monday March 12, 4:11 am ET
PharmaTracker submits: The Introgen (NasdaqGM: INGN) story, which received some interest of late in the blogosphere, is probably not even worth writing about. I have followed the story for a long time, read the bits and pieces of early data that have been published for their p53 gene therapy (called Advexin), but mostly followed with great humor the long, sordid tale of their alleged BLA filing for Advexin.
I thought I'd travel back in time to recount for the investing public what Introgen has been promising and repeatedly failing to deliver with respect to applying to the FDA for approval of Advexin. It is truly astonishing to see how badly this company failed to deliver on its promises, and really makes one wonder how they are able to continue raising capital to keep the whole thing afloat. It is amazing how much "credit" biotech investors are willing to extend to management teams that have done nothing to deserve any credibility.
My sources are conference call transcripts, SEC filings and press releases.
The dramatis personae for this tragicomedy are:
David Nance, President and CEO
Max Talbott, Senior VP, Worldwide Commercial Development
Bob Sobol, Senior VP, Medical and Scientific Affairs
Various analysts who asked questions on the conference calls
And now on to Act I....
Introgen’s 2002 10K, filed March 31, 2003, lays the background for the story:
“We are conducting pivotal Phase 3 clinical trials of ADVEXIN gene therapy in head and neck cancer. Pivotal Phase 3 trials are typically the final trials required for FDA approval. We have completed a Phase 2 clinical trial of ADVEXIN gene therapy in non-small cell lung cancer, a category that includes approximately 80% of the various types of lung cancer, and are developing FDA registration plans.”
Later, they wrote:
“Based on clinical results from our Phase 1 and Phase 2 clinical trials, we are currently enrolling patients in and conducting two multi-national pivotal Phase 3 clinical trials that the FDA has reviewed, and if successful, will be used to support regulatory approval.”
As of the August 12, 2003, second quarter conference call, the company was clearly saying it would file the Advexin BLA in 2004. Max Talbott said:
“As discussed in previous calls it is our plan to file the BLA for ADVEXIN and head and neck cancer in 2004” and later reiterated “So our guidance has been and continues to be, and as I reiterated a few moments ago, that we will file the BLA in 2004 and we're on target for that objective.”
This is not “initiate the filing,” not “ask the FDA if we might file,” not “begin to think about whether or not we should file for accelerated approval” – no, it is crystal clear. Introgen said they would file the Advexin BLA in 2004. That of course means that the company expected to complete its phase III trials in 2004 and then put together the BLA filing and turn it over to the FDA.
On the third quarter call (November 12, 2003) nothing had changed. Max Talbott:
“All aspects of the Advexin development program are on track to enable the submission of our biological license application in 2004.”
David Nance was equally confident:
“As we have provided guidance previously, we and as Max Talbot just reiterated, we will be filing a BLA for Advexin next year in 2004.”
And so too on the next conference call, on February 27, 2004. David Nance commented: “We are moving closer to our goal of filing a BLA, Biologics (inaudible) license, application for ADVEXIN later this year” and of course Max Talbott sang the same tune:
“By way of an update today, I'm very pleased to report to you that all of our trials and development processes remain on track for filing of our BLA this year. In the very near future, we will begin our pre-BLA meetings with the FDA to prepare for a submissions filing later this year. During these meetings, we will be reviewing with the agency our chemistry, preclinical and clinical data, the latter of which will include Phase II and Phase III data.”
But by May 11, 2004 (the first quarter 2004 conference call), the story had already begun to change meaningfully. Now, Introgen would merely begin the filing of a rolling BLA submission in 2004. David Nance: “With respect to our lead product
ADVEXIN, we remain on track to begin the BLA submission this year.”
Max Talbott:
“As we have previously reported, we remain on track for the initiation of our BLA submission this year.”
And Bob Sobol:
“Well, as we mentioned, we, you know, planned to file, begin the filing process for the BLA in 2004 by the end of this year. And it is really the results of those meetings that we've mentioned that are planned for the FDA with the FDA over the next several months that will determine the BLA filing options that we will pursue. And also that will dictate the time lines for completing our Phase III trials.”
So in just three months, we’ve gone from submitting a BLA in 2004 (which implies that the phase III trials would have been complete and analyzed) to initiating a rolling BLA. Moreover, the phase III trials are still enrolling patients so they are, in fact, not even close to being completed. And furthermore – how could the discussions with the FDA have anything to do with “the time lines for completing” the phase III trials? The timelines for a clinical trial are determined by how many patients are to be enrolled, how quickly on finds and enrolls the patients, and how long it takes patients to reach the primary endpoint. The size and primary endpoint are specified in the protocol, and the rate of accrual has nothing to do with the FDA at all.
The next two conference calls (a post ASGT-ASCO call in Jun 2004 and the second quarter call in August, 2004) reiterated this meaningfully pushed back timeline of “initiating” the BLA filing by year-end 2004. But on the third quarter 2004 call (November 8, 2004), management made no mention about the initiation of the BLA filing by year end, despite the fact that it should have been nearly ready to go. And they did not address the issue even when asked directly about it!
A December 23, 2004 press release provided a further twist to the company’s prior guidance:
“Introgen announced that it has filed a Request with the U. S. Food and Drug Administration [FDA] to accept a "rolling Biologics License Application" (rolling BLA) for ADVEXIN. Introgen also plans to seek Accelerated Approval of ADVEXIN . . . . Introgen has decided to pursue Accelerated Approval for ADVEXIN. The company is requesting that the Accelerated Approval rolling BLA begin immediately, with the completion of the filing process before the end of next year.”
So the company failed to “initiate” the filing of its BLA by year-end 2004 – rather, it merely told the FDA it intended to file a rolling BLA for Advexin! As of March 14, 2005 (the fourth quarter 2004 conference call) the submission of the rolling BLA still had not yet started.
Max Talbott:
“Introgen filed a request for the submission of portions of an application, called a SoPA with the agency. SoPA term is used to describe rolling NDA's and BLA's. SoPA request is the first regulatory step of our rolling BLA accelerated approval process. In conjunction with the SOPA request filing, Introgen also submitted its first BLA technical selection to the ADVEXIN IND for a pre-review evaluation.”
A SoPA is defined as a “submission of portions of applications". Introgen had merely submitted a request to the FDA that it be allowed to submit the Advexin BLA in pieces, commonly known as a rolling BLA. Let’s be clear – this is NOT in any way the “initiation” of a rolling BLA submission.
On that March 2005 conference call, David Nance could not even articulate a cogent reply to an analyst who asked about the status of the phase III data. Mark Gross asked"
“My understanding from last year was that your plan was to file, to begin the BLA filing process at the beginning -- I'm sorry, at the end of last year, and to finish it roughly by the end of this year. And that was before you decided to file mainly on the Phase II data. Implicit in that is that you would have the Phase III data well before the end of the year in order to complete the BLA process based on the Phase III data, if that had been your decision. So I'd like to ask whether you still expect to have the Phase III data available before the end of this year?”
David Nance’s reply is worthy of being cited in its entirety:
“You know, there are a number of options that I may ask Max Talbott o comment on, but again, I think -- I think your analysis is flawed because it does not include the appropriate number of variables, and I'm not sure to be, you're a bright guy, of course, and to be fair, I'm not sure that anybody can -- could include the number of variables because there are so many moving parts. So, in late December, the reporting quarter, we announced that the Company had taken the decision to request an accelerated approval and we -- in this call and previously have laid out the rationale for that request, and I think that because of the complexities and the complexities, for example, will we do interim analyses? And if so will the agency allow us to do it on, you know, a number of patients, a certain number of patients that had been treated? And there are almost endless permutations of examples that indicate that you really, you know, we announce material events when they occur and we think that our strategy announcement and our filing in December speaks for itself.”
That is quite a long non-answer to a simple yes or no question – will the phase III data be out in 2005?
Also in March 2005, Introgen appeared to make a material mis-statement in its 10K filing:
“The design of our two Phase 3 clinical trials was agreed to by the Food and Drug Administration, or FDA, under its Special Protocol Assessment program, and we have received Fast Track designation for ADVEXIN therapy from the FDA.”
A special protocol assessment [SPA] is when the FDA and a company agree to the design of a phase III trial, then the company goes out and actually runs the trial – the SPA generally states that if the trial is successful, it will support approval of the drug in question. To my knowledge, Introgen had never previously stated that the phase III program was being conducted under an SPA. More on this detail later.
On the May 2005 conference call reviewing the first quarter of 2005, Max Talbott re-iterated the company's commitment to getting Advexin onto the market soon:
“The soon er that we can make this product available, the sooner victims of head and neck cancer will have a therapy to ease their suffering and perhaps prolong their lives . . . . As you know, we have announced the initiation of our rolling BLA process and our plans to seek an accelerated approval rolling BLA for ADVEXIN in head and neck cancer.”
Notice they did not announce the initiation of a rolling BLA – rather “the initiation of our rolling BLA process.” Max also noted “our phase III trials are continuing.” And once again, in response to a direct question about enrollment in those phase III trials, David Nance waxed unintelligibly:
“Our management believes that, we are well advised and it's just not in the interest of the shareholders we believe, to speculate on all the possibilities and options that are available to the Company as we move through the process with the Agencies. So I appreciate your curiosity, certainly, I appreciate that. And hopefully you and the other listeners can appreciate how committed the Company is to making sure that we successfully register ADVEXIN. And also utilize the options which are numerous that are available to us as part of the iterative process with the Agency.”
On the August 9, 2005 conference call, there was still no statement from the company as to whether or not it had actually submitted any portion of the BLA to the FDA. In fact, the company had not even said whether or not the Agency had approved its request for a rolling BLA. It is more of the same. From Max Talbot:
“I’ve previously described in detail our overall regulatory strategy for the registration of ADVEXIN for recurrent head and neck cancer, and our plans continue to be consistent with our previous guidance. We are in ongoing contact with the US Food and Drug Administration and are continuing to implement the regulatory plan that we described at the time of our biologic license application -- BLA -- request to the agency in December 2004.”
On that second quarter 2005 conference call, the SPA issue reared its head. In response to a direct question about whether or not the company had obtained an SPA since the 10K had explicitly stated an SPA was in place, David Nance responded:
“Okay. We do have a protocol assessment from the agency and have those documents that we’ve disclosed. It’s not a special protocol assessment. When we received the protocol assessment – correct me if I’m wrong, Max -- there was no “special” available."
And Max Talbott supported this claim from David Nance:
“No, you’re absolutely right. David, special protocol assessment provisions, I think, came along about a year after.” David Nance added: “Well, just for the record, it should be a protocol assessment, but it has all the bells and whistles of an SPA. We just had the value of it for 12 months or 18 months ahead of the standard term.”
So first the company had clearly stated in its SEC filing from March of 2005 that it had an SPA. When asked, they denied it and said their conversations with the agency took place before there was an SPA process, but they had a “protocol assessment” which has all the “bells and whistles” of an SPA. Well the main “bell and whistle” of an SPA is the written commitment from the agency that if a trial is executed in the way it was designed and the results are positive, then those results will support an approval. Do they have such a commitment or not? I think the answer to that question is clear. Oh, by the way, subsequent SEC filings have referred to a “protocol assessment” but not an SPA.
On the November 2005 all, the company did not answer a direct question about whether the rolling BLA submission would be completed in 2005 or not. In December 2005, yet another twist in the saga occurred when the company announced in a press release that it had made a “proposal to the U.S. Food and Drug Administration [FDA]to request permission to accelerate the initiation of an interim analysis of its randomized, controlled phase 3 ADVEXIN clinical trial data ahead of schedule.”
On the fourth quarter 2005 conference call, which took place almost exactly one year ago in March 2006, Max Talbott told us “I'm pleased to announce, that this proposal has been accepted by the agency who has endorsed expediting the analysis. FDA has additionally commented that the information from this safety analysis will be useful in the review of our BLA. We have also responded to multiple FDA suggestions that we consider doing previously unplanned interim efficacy analyses for one or both of the Phase 3 studies that will be useful in the approval of the Advexin BLA.”
And in a routine that had been played several times before, David Nance gave a non-answer to the very direct question “when are you going to file the last section of the BLA for Advexin?” David’s reply: “Max, you can comment if you want to. It will be brief, I'm sure, but we're not giving particular guidance. As you know, a BLA is completely filed when all the sections are in. We are providing data to the agency sequentially. We have a pending request for accelerated approval. We have a confirmatory trial strategy that is coming into place that Max has described to you with our interim efficacy analysis on page 3. I don't think there is an answer that we can give you for that particular question.” I think a better question would have been “when do you intend to submit the first section of the BLA for Advexin?”
Moving to the May 16, 2006 conference call, the company purported to give an update on the interim safety analysis of the phase III trial P301. Max Talbott said:
“We previously announced that we had not yet reached the predefined point of 109 survival events in the study even though more than enough patients have been enrolled for a sufficient length of time to achieve that point. We proposed to the FDA that we be allowed to accelerate the initiation of the analysis and the FDA has agreed to that. In addition, the actual analysis approach has been agreed to with the FDA, and we are confident that the comparative analytical approach that we are taking will result in findings that substantiate the safety of ADVEXIN.”
Now why would they be discussing the “analysis approach” with the FDA at this point when the statistical analysis is pre-specified in the trial protocol? And how is it possible that they are supposedly in the middle of a rolling BLA submission yet they are still discussing with the FDA which data from which trials is going to be part of that submission? I have been following the biotech industry for 10 years and I have never seen companies engage in discussions with the FDA about what data to include in a BLA or NDA AFTER the application has been filed.
Again, I think the only question to ask here is “has a BLA, rolling or otherwise, actually been filed with the FDA?” Max Talbott’s words on this call would suggest not:
“Since as part of our US rolling BLA efforts, we’ve completed or have nearly completed the other technical sections -- for example, the pre-clinical manufacturing of the application, we have all the critical elements of a registration document prepared with the exception of a specific clinical section addressing the Li-Fraumeni Syndrome indication. Even a clinical safety section would be available to us based on our over 600 ADVEXIN- treated patients.”
Notice the phrase “our rolling BLA efforts,” and not “our rolling BLA.” Also note his comment “even a clinical safety section would be available to us” – clearly implying that such a section does not yet exist, but it could exist, in theory, were someone to compile the safety data on the 600 patients who have received Advexin over the years.
In a July18, 2006 conference call, this thorny question about the filing of an Advexin BLA came up again: an analyst asked “what work remains to be completed, if any, to file in the United States for accelerated approval . . . in other words it appears for me that you have all of your data now, it has been analyzed, you know, what needs to happen now, if anything?!
And the answer is that there’s almost nothing left to do! Max Talbott answered “Basically just reaching agreement with the Agency, and what format they want it.” And he elaborated further
“It's administrative I have done it, well, I have done it nearly three dozen times on approved drugs both here and abroad, so this is something that over the last 35 to 40 years I have been doing at least once a year, and in many instances, it's just administrative, really. And so I don't mean to minimize the effort, but as far as the complexity is concerned, once we have reached an agreement with the Agency of the administrative format they want it in, then the hard work has been done. The discovery, the analysis, the correlation, the actual clinical trials themselves, those are fait accompli.”
Well once again, it is not exactly clear why if they are in the middle of a rolling BLA they would be having a conversation with the agency over the format of the BLA? But truly the most amazing thing we learned here is that “the discovery, the analysis, the correlation, the actual clinical trials themselves, those are fait accompli.”
Not so fast . . . less than one month later, on the second quarter 2006 conference call, everything seems to have come crashing to a halt. Now, all the data will be interpreted in light of some poorly articulated biomarkers. This, the company believes, will EXPEDITE the approval of Advexin, which in 2003 the company said was ready to go to the FDA in 2004! Max Talbott sounded triumphant:
“As we announced today, we have reached agreement with FDA to not only use these biomarkers in our analysis of our Phase II data, but also to incorporate these useful predictive tools in the interim efficacy analyses that we will be performing on our ongoing Phase III trials. This is an absolutely essential element of our accelerated approval enrolling BLA regulatory process. With FDA's previous invitations to consider interim efficacy analysis for the Phase III studies, we are now prepared, in conjunction with the FDA, to conduct these analyses. As we've indicated on several previous occasions, our BLA will utilize both Phase II and Phase III data for analyses. These analyses will be informed or are already in-hand biomarker intelligence and will allow us to provide package insert information specifically targeting patient characteristics.”
BUT WAIT – a few weeks earlier he told us “the discovery, the analysis, the correlation, the actual clinical trials themselves, those are fait accompli” and that all that stood in the way of a complete BLA filing was a question of the formatting of the BLA! Now they are going to have to engage in all sorts of new, non-prespecified analyses of phase III trials that have not even completed enrolling?
And read what the company was talking about – product labels! Despite not having completed phase III, not having released any of the interim analyses, not having any idea what the “biomarker” analysis of the phase III interim data will look like, and despite supposedly being in the middle of a rolling BLA submission for accelerated approval based on the uncontrolled phase II studies!
Max Talbott again:
“As mentioned during their remarks on the July 17 teleconference, Introgen and FDA are currently in the proces s of reaching agreement on the formats and mechanics to be employed in continuing the final regulatory activities. We believe that our available Phase II and soon-to-be-available Phase III data are more than sufficient for our regulatory approval processes. We believe that the package insert language, though, that we develop from these data will allow ADVEXIN to describe a superior safety and efficacy profile as compared to those profiles now available for existing recurrent head-neck cancer products.”
Later he said more:
“That's a good preface to the fact that the, I think what's really key about all of this is that we're, we applied the biomarker findings to the Phase II data, but clearly we had to get the agency's agreement to prospectively apply biomarker findings in the analysis, the interim safety analysis--excuse me, the interim efficacy analysis for the two ongoing Phase II trials. And that, I think, speaks to the issue of using these data in a prospective fashion to ask the right questions, to demonstrate the efficacy of ADVEXIN in both of these circumstances. I made an allusion to the fact of the package insert in my comments earlier today. Realize, of course, those of you that have been following us for a long time, these are ongoing trials, one of which is a monotherapy comparison, and the other which is the use of ADVEXIN in combination. So theoretically, then, as we move forward, not only would we have a monotherapy indication for ADVEXIN in recurrent squamous cell head-neck cancer, which Erbitux received earlier this year with 103 patients worth of data, I think. But it's very conceivable and likely, in fact, that the package insert will contain reference to combination use of ADVEXIN as well.”
And the old SPA issue came up again – again, Max Talbott:
“We will utilize what's called an SPA or Special Protocol Assessment to record and maintain all of these agreements, simply because the agency, I think, has long favored that approach. And it will be one which will, in fact, make our life a lot easier as we move into the actual approval itself.”
Now how are they going to get an SPA for a trial that was designed 5 years ago, has been enrolling patients over that whole time, and is not being subjected to multiple unplanned interim analyses?? The very idea defies the imagination! But David Nance threw some cold water on the conversation:
“I want to make sure that we are not announcing that an accelerated approval, based only on the Phase II data, is being announced, nor are we stating that the accelerated approval will require the Phase III data, and that the Phase III data might be used as a confirmatory analysis. So we're not saying anything. We're just saying other than we have agreed with the agency that we may use the biomarker data, and we're working out the precise details, and I wouldn't rule out either possibility.”
I think his comment says it all – “we're not saying anything” – that is exactly what Introgen has been doing for years. Not saying anything. So at year-end 2006, now 2 years after the BLA was supposed to have been filed, Introgen issued a press release announcing a conference call to “update its regulatory and clinical developments including its plans to begin the analyses of Phase 3 ADVEXIN trials. Management will comment upon the agreement between Introgen and the Food and Drug Administration for the statistical analysis plan of ADVEXI N phase 3 clinical trials to support product licensure for recurrent head and neck cancers.” On that call, David Nance said “Introgen and FDA have agreed on the statistical analysis plan for the ADVEXIN Phase III clinical trials to support product licensure for recurrent head and neck cancers. The analyses will incorporate p53 protein and other biomarkers. Our recently reported clinical biomarker data has provided extremely high statistical significance for both survivals and tumor response in p53 biomarker-defined patients. We plan to initiate the analyses of the Phase III ADVEXIN trials in early 2007.” So instead of filing a BLA in 2004, they will be beginning INTERIM analyses of the pahse III data in 2007!!
That brings us to yesterday’s fourth quarter 2006 conference call. Max Talbott put it on the line:
“The Company will begin the Phase 3 efficacy analysis in the second quarter of 2007. As we previously reported, a sufficient number of patients have been treated in the Phase 3 trial to provide us with meaningful efficacy data from these analyses. These efficacy analyses will be completed, and all remaining elements of the FDA registration submission will be concluded, recurrent head and neck cancer in 2007.”
He reiterated this guidance:
“One, we have formally amended the Phase 3 statistical analysis plan in preparation for opening of our study database. Two, we will begin the efficacy analysis of our Phase 3 data next quarter. Three, next quarter we will submit to FDA our final analysis set of the ADVEXIN Phase 2 data, to include our most recent biomarker findings. And, four, in 2007, we will complete the submission to FDA of all elements of the BLA for head and neck cancer.”
But when asked if the company would make the results of its phase III analyses public when complete, David Nance hedged:
“Yes, I just think, Bob, I [inaudible] my answer by the calendar date, so we've given a range of within two quarters. It's clear that the activities will ensue in the -- between those dates we mentioned and before the end of the year, and we'll provide the information to FDA, and, depending on the time in the year, we may publish. We will be making publications at conferences, as we usually do, and so, I'll say again, it's possible, depending on how the process goes and the precise timing between now and the end of the year.”
Mark your calendars. By the end of this year the Advexin BLA will be filed (we’ve heard that before). That means a 2008 review and decision. Hopefully, they have cobbled together enough data so they don’t merely get an RTF letter and we can all enjoy reading a detailed FDA review before they get skewered at an Oncology Drugs Advisory Panel. Either way, 2008 should see this story come to a close. Mercifully.
Disclosure: The author has a short position in INGN
re DNAG...what, you bought their stock at a $1+ and saw it drop all the way to a penny, and now you're trying to pump up the price to two pennies so you can sell?
lol
As you can see, pretty sane. As for the post you referred to, you could be right, but the poster didn't elaborate.
Nothing like an unsolicited but cutting edge analysis. At least you backed up your conclusions with well-organized arguments.
DNDN Read Me First
Edits: From I-Village, a good summary of DNDN/Provenge story to date, with an opinion at the end
http://tinyurl.com/2kv2t4
and froggmister's latest DNDN links page
http://tinyurl.com/2q4gqe
---------------------------------------------------------------------------------------
All-cause mortality from 9901 Phase III trial presented by Dr. Eric Small at Prostate Cancer Foundation Scientific Retreat 10/20/06 (compilation of several I-Hub posts)
#msg-14152660
Notes from DNDN presentation at UBS Conference, 9/27/06, Dr. Gold presenting, courtesy of yarbonero on I-Village board
http://tinyurl.com/ftn75
Rancherho's 7/17/06 post on CD54 upgregulation, memory T-cells, and long-term survival
http://tinyurl.com/k24et
Dr. Scott Gottlieb's Feb 2005 Forbes column on Provenge; in 2/05 he was editor of a biotech newsletter, in 8/05 he became #2 at the FDA
http://tinyurl.com/43cvh
PubMed entry regarding Provenge, courtesy of thenewthinker on the Yahoo msg board
http://tinyurl.com/oavgx
PR regarding publication of the P-16 trial (Provenge+Avastin) in AIPC
http://biz.yahoo.com/prnews/060607/sfw079.html?.v=56
Several webcast presentations, including Provenge/JMP Securities/trial doctors conference call from 5/11/06
http://investor.dendreon.com/medialist.cfm
http://tinyurl.com/j9k4g
Go to: Transcript for Feb. 9, 2006
Potency Testing for Autologous Cellular Therapy
Nicole Provost PhD.
P. 131
Go to: Slides February 9,2006
From DNDN yahoo MB posted by zurdoc1...link below
http://tinyurl.com/gjnbv
spartex points out that Nicole Provost's presentation and panel questions start on page 135 in the link below.
http://tinyurl.com/fdgg8
P-11, or PROTECT Phase III for androgen-dependent prostate cancer
http://tinyurl.com/dmshb
Dr. Gold's presentation and Q&A notes at Bio-CEO conf in NYC 2/24/06
http://tinyurl.com/5hkvt
http://tinyurl.com/7w8gx
http://tinyurl.com/b6xug
9901 and 9902a Kaplan-Meier survival curves:
#msg-8677219
ECCO/Higano/9902a presentation:
http://www.sessions2view.com/ecco05c1/index.php
[Directions:
1.Click on acceptance box on bottom of screen.
2.Click on ENTER button at bottom of screen.
3. Click on Speakers link at bottom of screen.
4. Click on the letter “H” for Dr. Higano.
5. Click on one of the three icons for the slides, audio, and transcript, respectively. (The presentation audio can be cued from any individual slide.)
6. Slide #16 has the 9902a Kaplan-Meier survival curves.]
Dr. Sternberg’s 5-minute reply to Dr. Higano’s presentation:
#msg-8567652
Three most recent webcasts (10/31 conf call on Provenge 9902A trial results at ECCO, 11/4 conf call on Q3 financial results, 11/7 webcast at Rodman & Renshaw conference)
http://investor.dendreon.com/medialist.cfm
UBS 9/27/05 Conference Call Transcript and Breakout Session Notes
#msg-7922336
Dr. Eric Small presentation of 9901 trial results at May 2005 ASCO Conference
http://tinyurl.com/e2ceu
DNDN newsroom for investors
http://investor.dendreon.com/newsroom/
Discussion thread of some clinical trial summations on competitive hormone-refractory prostate cancer treatments (courtesy of rancherho)...thread continues with surrogate endpoint discussion and links
http://tinyurl.com/8syxr
http://tinyurl.com/99kfb
http://tinyurl.com/armgl
http://tinyurl.com/bnscm
http://tinyurl.com/7ozey
http://tinyurl.com/89h5p
http://tinyurl.com/ey5tf
http://tinyurl.com/99bdm
DNDN’s 9901 data-release CC (2/22/05):
http://investor.dendreon.com/medialist.cfm
ASCO Prostate Cancer presentation Dr. Eric Small 2/19/05:
http://tinyurl.com/4b7to
Provenge potential market:
http://tinyurl.com/7dwm6
http://tinyurl.com/3k857 (“Duh, yes”)
FDA Prostate Cancer Workshop 6/04 (change to Transcript2.pdf and 3.pdf for continuation)
http://www.fda.gov/cder/drug/cancer_endpoints/ProstateTranscript1.pdf
9901 trial Gleason score breakdown (we now know that 4 out of 5 surviving placebo arm patients crossed over to receive salvage Provenge after progression)
http://tinyurl.com/5v6xy
ASCO Prostate message-board musings by walldiver (2/05)
http://tinyurl.com/5hykx
http://tinyurl.com/4ssxf
The ever-changing short-seller arguments (inspired by David Miller)
#msg-5875436
DNDN Insider Transactions
http://finance.yahoo.com/q/it?s=DNDN
Basic facts about prostate cancer
http://www.cancer.gov/cancertopics/types/prostate
http://www.acor.org/cnet/glossary/45696.html
The Genta and Allos ODAC meeting on 5/3/04 was the tipping point for the new strategy. Once they saw that Pazdur was going to impose his will on development-stage biotechs without McClellan around to rein him in, they doubled down, and the new hedge funds that have been formed since mid-2004 also use this same strategy of shorting development-stage bios.
This strategy has been validated so far judging from all the Phase III blowups, with only a few exceptions.
Hedge fund activity in biotech was not nearly as widespread back in 2004 as it is now. Same thing with the "market neutral" hedge funds. There are so many more of them now, probably by a factor of 2 to 4, than there were then. They all have the same playbook. Go long big biotech, go short development-stage biotech.
3/27 FDA Briefing Documents...scroll down to appropriate committee
http://www.fda.gov/ohrms/dockets/ac/07acdocs.htm
HEPH dropped about 25% right before 4PM and has dropped another 25% after hours. I wonder how their govt contract negotiations are going?
Looks like Dean Wormer has invented a new category for INGN: Triple Super Secret Probation
Apparently Bluto lent his wristwatch to the INGN execs after he became Senator.
I don't think you're attacking DNDN, jellybean...far from it, in fact. I had forgotten about the fact that the control arm in the DN-101 trial was that Taxotere regimen that doesn't extend survival...so thanks David. I'm pretty sure that the new DN-101 Phase III will have once per three week Taxotere as the control arm.
I think if DN-101 had modified the Taxotere side effects to a much greater extent than it did, NOVC may have been able to talk the FDA into assenting to a filing and convening an advisory panel meeting. It looks like the overall dataset is much stronger than Xinlay's. It would have been interesting to see if it would have been approved or not.
The overall survival data for NOVC's trial you're referring to was extrapolated into the future at the time of FDA consultations since it was not yet mature.
NOVC updated the trial data recently at the ASCO Prostate Symposium, and did not release median survival numbers in the PR, nor did they release log rank p values. Overall survival for Asentar in the 250-pt trial thus seems not to have been statistically significant measured by log rank, only by Cox regression. The p value measured via Cox was between 0.03 and 0.04. I don't know if Cox regression was prespecified in the SAP for the Asentar Phase II. However, the Asentar 250-pt trial population can be compared fairly accurately to Provenge's 225-pt 9901+9902A population. NOVC's survival p value of 0.03-0.04 measured by Cox doesn't compare well to DNDN's 0.00006 measured by the same analysis.
<<e) It is likely that 9902a doesnt work as a stand-alone trial (I would welcome your opinion on this, as you have seen it debated here) using the pre-specified CR mthodology, as not enough of the imbalanced prognosticators come up significant to be advanced into the multi-variate model. But given the circumstances of the imbalances, and particularily c) above, it is essential, if the true effect of Provenge is to isolated, that a CR for these imbalances be performed.>>
I would disagree pretty strongly with you on this one. It's apparent that the number of bone mets has a very strong inverse correlation with survival. The other two stat sig covariates that 9901 and 9902A have in common are localization of disease and PSA at baseline. If you take 9902A and start with the 20 factors in the Halabi nomogram, I would submit that you will end up with at least those three upon completion of the Cox regression exercise, which would likely be enough for stat sig survival via Cox.
DNDN Read Me First
Edits: housecleaning
All-cause mortality from 9901 Phase III trial presented by Dr. Eric Small at Prostate Cancer Foundation Scientific Retreat 10/20/06 (compilation of several I-Hub posts)
#msg-14152660
Notes from DNDN presentation at UBS Conference, 9/27/06, Dr. Gold presenting, courtesy of yarbonero on I-Village board
http://tinyurl.com/ftn75
Rancherho's 7/17/06 post on CD54 upgregulation, memory T-cells, and long-term survival
http://tinyurl.com/k24et
Dr. Scott Gottlieb's Feb 2005 Forbes column on Provenge; in 2/05 he was editor of a biotech newsletter, in 8/05 he became #2 at the FDA
http://tinyurl.com/43cvh
PubMed entry regarding Provenge, courtesy of thenewthinker on the Yahoo msg board
http://tinyurl.com/oavgx
PR regarding publication of the P-16 trial (Provenge+Avastin) in AIPC
http://biz.yahoo.com/prnews/060607/sfw079.html?.v=56
Several webcast presentations, including Provenge/JMP Securities/trial doctors conference call from 5/11/06
http://investor.dendreon.com/medialist.cfm
http://tinyurl.com/j9k4g
Go to: Transcript for Feb. 9, 2006
Potency Testing for Autologous Cellular Therapy
Nicole Provost PhD.
P. 131
Go to: Slides February 9,2006
From DNDN yahoo MB posted by zurdoc1...link below
http://tinyurl.com/gjnbv
spartex points out that Nicole Provost's presentation and panel questions start on page 135 in the link below.
http://tinyurl.com/fdgg8
P-11, or PROTECT Phase III for androgen-dependent prostate cancer
http://tinyurl.com/dmshb
Dr. Gold's presentation and Q&A notes at Bio-CEO conf in NYC 2/24/06
http://tinyurl.com/5hkvt
http://tinyurl.com/7w8gx
http://tinyurl.com/b6xug
9901 and 9902a Kaplan-Meier survival curves:
http://www.investorshub.com/boards/read_msg.asp?message_id=16967630
ECCO/Higano/9902a presentation:
http://www.sessions2view.com/ecco05c1/index.php
[Directions:
1.Click on acceptance box on bottom of screen.
2.Click on ENTER button at bottom of screen.
3. Click on Speakers link at bottom of screen.
4. Click on the letter “H” for Dr. Higano.
5. Click on one of the three icons for the slides, audio, and transcript, respectively. (The presentation audio can be cued from any individual slide.)
6. Slide #16 has the 9902a Kaplan-Meier survival curves.]
Dr. Sternberg’s 5-minute reply to Dr. Higano’s presentation:
#msg-8567652
Three most recent webcasts (10/31 conf call on Provenge 9902A trial results at ECCO, 11/4 conf call on Q3 financial results, 11/7 webcast at Rodman & Renshaw conference)
http://investor.dendreon.com/medialist.cfm
UBS 9/27/05 Conference Call Transcript and Breakout Session Notes
#msg-7922336
Dr. Eric Small presentation of 9901 trial results at May 2005 ASCO Conference
http://tinyurl.com/e2ceu
DNDN newsroom for investors
http://investor.dendreon.com/newsroom/
Discussion thread of some clinical trial summations on competitive hormone-refractory prostate cancer treatments (courtesy of rancherho)...thread continues with surrogate endpoint discussion and links
http://tinyurl.com/8syxr
http://tinyurl.com/99kfb
http://tinyurl.com/armgl
http://tinyurl.com/bnscm
http://tinyurl.com/7ozey
http://tinyurl.com/89h5p
http://tinyurl.com/ey5tf
http://tinyurl.com/99bdm
DNDN’s 9901 data-release CC (2/22/05):
http://investor.dendreon.com/medialist.cfm
ASCO Prostate Cancer presentation Dr. Eric Small 2/19/05:
http://tinyurl.com/4b7to
Provenge potential market:
http://tinyurl.com/7dwm6
http://tinyurl.com/yt9csp (“Duh, yes”)
FDA Prostate Cancer Workshop 6/04 (change to Transcript2.pdf and 3.pdf for continuation)
http://www.fda.gov/cder/drug/cancer_endpoints/ProstateTranscript1.pdf
9901 trial Gleason score breakdown (we now know that 4 out of 5 surviving placebo arm patients crossed over to receive salvage Provenge after progression)
http://tinyurl.com/5v6xy
ASCO Prostate message-board musings by walldiver (2/05)
http://tinyurl.com/5hykx
http://tinyurl.com/4ssxf
The ever-changing short-seller arguments (inspired by David Miller)
#msg-5875436
DNDN Insider Transactions
http://finance.yahoo.com/q/it?s=DNDN
Basic facts about prostate cancer
http://www.cancer.gov/cancertopics/types/prostate
http://www.acor.org/cnet/glossary/45696.html
Thanks Dew, eom
DNDN Read Me First
Edits: All-cause mortality from 9901 Phase III trial presented by Dr. Eric Small at Prostate Cancer Foundation Scientific Retreat 10/20/06 (compilation of several I-Hub posts)
#msg-14152660
Notes from DNDN presentation at UBS Conference, 9/27/06, Dr. Gold presenting, courtesy of yarbonero on I-Village board
http://tinyurl.com/ftn75
Rancherho's 7/17/06 post on CD54 upgregulation, memory T-cells, and long-term survival
http://tinyurl.com/k24et
Dr. Scott Gottlieb's Feb 2005 Forbes column on Provenge; in 2/05 he was editor of a biotech newsletter, in 8/05 he became #2 at the FDA
http://tinyurl.com/43cvh
PubMed entry regarding Provenge, courtesy of thenewthinker on the Yahoo msg board
http://tinyurl.com/oavgx
PR regarding publication of the P-16 trial (Provenge+Avastin) in AIPC
http://biz.yahoo.com/prnews/060607/sfw079.html?.v=56
Several webcast presentations, including Provenge/JMP Securities/trial doctors conference call from 5/11/06
http://investor.dendreon.com/medialist.cfm
http://tinyurl.com/j9k4g
Go to: Transcript for Feb. 9, 2006
Potency Testing for Autologous Cellular Therapy
Nicole Provost PhD.
P. 131
Go to: Slides February 9,2006
From DNDN yahoo MB posted by zurdoc1...link below
http://tinyurl.com/gjnbv
spartex points out that Nicole Provost's presentation and panel questions start on page 135 in the link below.
http://tinyurl.com/fdgg8
P-11, or PROTECT Phase III for androgen-dependent prostate cancer
http://tinyurl.com/dmshb
Dr. Gold's presentation and Q&A notes at Bio-CEO conf in NYC 2/24/06
http://tinyurl.com/5hkvt
http://tinyurl.com/7w8gx
http://tinyurl.com/b6xug
9901 and 9902a Kaplan-Meier survival curves:
#msg-8677219
ECCO/Higano/9902a presentation:
http://www.sessions2view.com/ecco05c1/index.php
[Directions:
1.Click on acceptance box on bottom of screen.
2.Click on ENTER button at bottom of screen.
3. Click on Speakers link at bottom of screen.
4. Click on the letter “H” for Dr. Higano.
5. Click on one of the three icons for the slides, audio, and transcript, respectively. (The presentation audio can be cued from any individual slide.)
6. Slide #16 has the 9902a Kaplan-Meier survival curves.]
Dr. Sternberg’s 5-minute reply to Dr. Higano’s presentation:
#msg-8567652
Three most recent webcasts (10/31 conf call on Provenge 9902A trial results at ECCO, 11/4 conf call on Q3 financial results, 11/7 webcast at Rodman & Renshaw conference)
http://investor.dendreon.com/medialist.cfm
UBS 9/27/05 Conference Call Transcript and Breakout Session Notes
#msg-7922336
Dr. Eric Small presentation of 9901 trial results at May 2005 ASCO Conference
http://tinyurl.com/e2ceu
DNDN newsroom for investors
http://investor.dendreon.com/newsroom/
Discussion thread of some clinical trial summations on competitive hormone-refractory prostate cancer treatments (courtesy of rancherho)...thread continues with surrogate endpoint discussion and links
http://tinyurl.com/8syxr
http://tinyurl.com/99kfb
http://tinyurl.com/armgl
http://tinyurl.com/bnscm
http://tinyurl.com/7ozey
http://tinyurl.com/89h5p
http://tinyurl.com/ey5tf
http://tinyurl.com/99bdm
DNDN’s 9901 data-release CC (2/22/05):
http://investor.dendreon.com/medialist.cfm
ASCO Prostate Cancer presentation Dr. Eric Small 2/19/05:
http://tinyurl.com/4b7to
Provenge potential market:
http://tinyurl.com/7dwm6
http://tinyurl.com/yt9csp (“Duh, yes”)
FDA Prostate Cancer Workshop 6/04 (change to Transcript2.pdf and 3.pdf for continuation)
http://www.fda.gov/cder/drug/cancer_endpoints/ProstateTranscript1.pdf
9901 trial Gleason score breakdown (we now know that 4 out of 5 surviving placebo arm patients crossed over to receive salvage Provenge after progression)
http://tinyurl.com/5v6xy
ASCO Prostate message-board musings by walldiver (2/05)
http://tinyurl.com/5hykx
http://tinyurl.com/4ssxf
The ever-changing short-seller arguments (inspired by David Miller)
#msg-5875436
DNDN Insider Transactions
http://finance.yahoo.com/q/it?s=DNDN
Basic facts about prostate cancer
http://www.cancer.gov/cancertopics/types/prostate
http://www.acor.org/cnet/glossary/45696.html
Io, no need to get worked up. I think we're going to have the last laugh. Let it go.
Medchal, I've got about 25 posters on the I-V board on ignore, the vast majority are pumpers or a few incessantly posting traders. It makes skimming through the main msg list go by pretty quickly.
<<DNDN: I assume that this is a negative since most people believed that the FDA would approve without a panel.>>
If you classify morons as "most people," then you would be correct.
Could be just the luck of the draw. Look at the 36-month survivors in the placebo arm. It wasn't everyone, just a higher %.
INGN article in SeekingAlpha blog...looks like the scammers are getting the full reaming from the biotech press.
SeekingAlpha
Introgen: Setting The Record Straight On Its Biomarker Claims
Tuesday February 27, 3:05 am ET
http://biz.yahoo.com/seekingalpha/070227/28098_id.html?.v=1
Charles Atan submits: The FDA's biomarker initiative and its relationship to Introgen's (NasdaqGM: INGN) proposed BLA for Advexin for the treatment of head and neck cancer will effectively determine Introgen's fate in the short term as well as the fate of Introgen's shareholders. Unfortunately, there has been no educated discussion from the Street about the FDA's stance on biomarkers and their applicability to NDAs and BLAs. Instead, the sellside focuses on and trusts completely in Introgen management. This unwavering trust has been abused by Introgen for many years. So let's take a look at a close look at what the FDA says about biomarkers.
ADVERTISEMENT
On February 14, 2006 the FDA issued a press release titled "New Federal Health Initiative to Improve Cancer Therapy". Introgen seized the moment and began a concerted effort to exploit an initiative that has no relevance to its 6 year old phase 2 data or its phase 3 trials as far as an FDA regulatory decision. Introgen's efforts began in force in May 2006 in its first quarter earnings announcement and subsequent conference call. On August 9, 2006, Introgen issued a press release stating that "the company and the FDA have reached agreement to incorporate the use of Introgen's biomarkers in the analysis of ADVEXIN clinical data in support of FDA approval of ADVEXIN p53 cancer therapy." The company further stated "We now plan to use the biomarkers to analyze our phase 3 patient data. The FDA has previously told the company that its Phase 3 trial data may be used for interim efficacy analyses".
And on a conference call on December 28, 2006, Introgen announced that they and the "FDA have agreed on the statistical analysis plan for the ADVEXIN Phase 3 clinical trials to support product licensure for recurrent head and neck cancers. The analyses will incorporate p53 protein and other biomarkers." The only statement of all of the foregoing that is remotely accurate is that Introgen plans to use the biomarkers to analyze their data. For all the FDA cares they can use an abacus or a slide ruler to analyze the data.
What is the Biomarker Initiative?
The first questions investors need to ask themselves are (1) what is the biomarker initiative, (2) how does the FDA define a biomarker and (3) what does Introgen mean when they say that the FDA has allowed them to use biomarker data to analyze their trials in support of approval.
The answer to the first question is that the biomarker initiative described in the February 14, 2006 FDA press release actually relates to a collaboration between the FDA, the National Cancer Institute and Medicare to improve and develop procedures for utilizing biomarkers in the DESIGN and analysis of clinical trials. As far as the FDA itself, the topic of pharmacogenomic tests and biomarkers in the context of drug development was previously set forth in great detail in an FDA guidance document dated March 2005. FDA, like Introgen says, welcomes the use of biomarker analysis from all drug sponsors on a voluntary basis. They do not, however, utilize the data for purposes of determining whether a BLA or a drug is approvable except in circumstances that are entirely different than the circumstances surrounding Advexin's ancient phase 2 studies and as yet incomplete phase 3 trials.
The FDA defines these voluntary types of submission as VGDs, or Voluntary Genomic Data Submissions. There are strict limitations set forth in the guidance with regard to how VGDs can be and will be used in the context of an NDA or BLA. FDA guidance repeatedly sets forth these limitations:
Data from a VGDS submission concerning a product under an IND will not be used for regulatory decision making...
The FDA will not use genomic information submitted through the voluntary process for regulatory decision making on INDs, BLAs, or NDAs...
Any data evaluation will be conducted for scientific and informational purposes — not for regulatory decision making.
Importantly, the purpose of the guidance set forth explicitly the FDAs intentions with respect to how the data would be used in regulatory decision making: "that is, when the data will be considered sufficiently reliable to serve as the basis for regulatory decision making; when it will be considered only supportive to a decision; and when the data will not be used in regulatory decision." Introgen's statements to investors explicitly state that their biomarker data will be used in a regulatory decision with regard to Advexin and that the FDA has agreed to do so. You can be 100% certain that this is not true.
While everyone may know what the term regulatory decision means, I'll set forth the FDA's definition in case there is any confusion. The term regulatory decision making "applies to decisions that FDA may make in the evaluation of pharmacogenomic information used to establish the dosing, safety, or effectiveness of a drug or biological product." The guidance further states that observational and exploratory biomarkers are insufficient for making a regulatory decision. It is clear that Introgen has done nothing more than make observations through the extensive exploration of their ancient phase 2 data and therefore it will not be used in the context of approval of Advexin.
The answer to the second question is that a biomarker, as defined by the FDA, is "A characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention." The FDA further breaks down biomarkers into two categories. These categories animate the FDA's potential use and interpretation of the biomarker and include (1) Known valid biomarkers and (2) Probable valid biomarkers. The FDA defines a known valid biomarker as:
A biomarker that is measured in an analytical test system with well-established performance characteristics and for which there is widespread agreement in the medical or scientific community about the physiologic, toxicologic, pharmacologic, or clinical significance of the results.
Clearly, Introgen's biomarkers have none of these characteristics and are therefore not considered a known valid biomarker. The FDA defines a probable valid biomarker as:
A biomarker that is measured in an analytical test system with well-established performance characteristics and for which there is a scientific framework or body of evidence that appears to elucidate the physiologic, toxicologic, pharmacologic, or clinical significance of the test results.
Introgen's p53 biomarker test may be measured in an analytical test system with well-established performance characteristics. Even if it is, however, the FDA tosses biomarkers into the "probable valid" bucket when "the data elucidating its significance has been generated within a single company" and "when independent verification of the test results may not have occurred." Both of these characteristics describe Introgen's p53 biomarker data.
Introgen will argue that there biomarker data is robust. However, here are the facts. An abstract from the First AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development reported on an analysis of the Introgen phase 2 studies with respect to the biomarkers. That abstract reports on data from 16 patients (which has somehow increased since the report was issued in September 2006) with known clinical outcomes and useable tumor samples. These 16 patients represent 7% of the total phase 2 population. The abstract was authored by Laura Licato, associate director for Clinical Research at Introgen and other Introgen employees, including Robert Sobol, both of whom stand to gain financially from the acceptance of their biomarker data.
This is not reliable evidence of the biomarker's validity and there is zero chance that the FDA will approve Advexin based on this biomarker outside of a de novo pivotal program.
Disclosure: Author has no position in INGN
Regardless, ideal enrollment for these final pts probably wouldn't have made the p value a whole lot better. The trial was just too small.
GTOP: the plot thickens...
http://biz.yahoo.com/bw/070226/20070226006286.html?.v=1
Press Release Source: Genitope Corporation
Genitope Corporation to Host Conference Call to Discuss Updated Blinded Data from Its Phase 3 Clinical Trial
Monday February 26, 4:52 pm ET
Conference Call Tuesday, February 27, 2007, at 4:30 p.m. EST
FREMONT, Calif.--(BUSINESS WIRE)--Genitope Corporation (Nasdaq:GTOP - News) today announced that it will be hosting a conference call on Tuesday, February 27, 2007, at 4:30 p.m. (EST) to discuss updated blinded data from its Phase 3 clinical trial of MyVax® personalized immunotherapy. The data will be included in a report on Form 8-K to be filed after 4:00 p.m. (EST) on Tuesday, February 27, 2007 with the Securities and Exchange Commission.
The dial-in number for U.S. and Canada is 1-800-260-8140 (passcode 75109878). The international dial-in is 1-617-614-3672 (passcode 75109878). The call can also be accessed in a listen-only mode on Genitope Corporation's Web site at www.genitope.com. The Web cast will be archived for 30 days.
About Genitope Corporation
Genitope Corporation (Fremont, Calif.) is a biotechnology company focused on the research and development of novel immunotherapies for the treatment of cancer. Genitope Corporation's lead product candidate, MyVax® personalized immunotherapy, is a patient-specific active immunotherapy based on the unique genetic makeup of a patient's tumor and is designed to activate the patient's immune system to identify and attack cancer cells. For more information on the company, please log on to http://www.genitope.com.
Contact:
Investor Contact:
Genitope Corporation
John Vuko, 510-284-3000
IR@genitope.com
or
Media Contact:
Edelman
Marites Cristobal, 323-202-1424
marites.cristobal@edelman.com
--------------------------------------------------------------------------------
Source: Genitope Corporation
re Threshold:
That's a tough result. It would be interesting to know the percentage of patients in each arm who received Tarceva on top of Gemzar. It also would be interesting to see if there were any QOL aspects of the trial in the SAP, and how they played out in each arm.
Magilla...Interesting stuff. Of course, when the music that accompanies it is from one of the greatest movie original scores ever, it makes it that much more compelling.
(Last of the Mohicans)
I don't believe the FDA cleared INGN to do anything. I do believe that one should take EVERY PUBLIC STATEMENT that INGN mgmt makes with a boulder-sized "grain" of salt.
Check out the Feuerstein articles on TheStreet.com. His take on INGN is actually less harsh than that of other writers and investors whom I've read or communicated with.
Correct. I was referring to INGN, not ALTH. I went long right after ALTH's negative panel meeting in 5/04 and sold out on the spike after the approvable letter. I have not bought back in since. I missed out on the runup, obviously.
One would hope that the panel would take the relative wellness of the two trials into consideration. Provenge did show median and three-year survival benefits in both trial populations.
Not much is known publicly about what happened in 9902A regarding those patients who enrolled in Apr 2002 or later, especially the specifics about ttp. I have no idea, and I don't think anyone outside the company has any idea either.
The data mining at INGN is far more egregious than the data mining ALTH did a few years ago. For one thing, ALTH actually ran a pivotal Phase III. They picked the wrong subgroup to try and get approval for, however. The brain mets from breast cancer subgroup comprised approx 25% of the ITT group. At least ALTH is now running a pivotal Phase III w/SPA for that subgroup. Probably a coin flip for stat sig.
In addition, ALTH has not done a reverse split. They've diluted somewhat, but the price is ~3 1/2 times where it was in May 2004 after they got thumbs down at ODAC. INGN's subgroup comprised approx 5-10% of the ITT group in its Phase III. Not only that, but the co is trying to cherry-pick patients from some of its Phase II trials in order to add them all together into a collective group to present to the FDA. The company is a scam, IMO.
I can't think of any data they are scheduled to release prior to the panel meeting.
Clinical / Regulatory / Litigation Calendar
[Please keep entries up to date! See updating procedure at the end of this post.]
NOTE: ANYONE MAY UPDATE THIS FILE
Edits: CVTX
ACHN – See GILD
ADLR – Approvable letter for Entereg issued 11/6/06 requesting safety data due in 2Q07.
AGIX – ARISE data at ACC March 24-27, 2007.
AMGN – Vectibix PACCE trial in 1st-line CRC (Avastin+FOLFOX+/-Vectibix) interim PFS based on 25% of events: 2Q07 (probably ASCO). (PACCE showed no benefit vs control in RR.) Vectibix final OS from ‘408’ study: any day (low chance of hitting endpoint).
AMLN – Phase-3 LAR results: 2H07; Byetta monotherapy results: 2H07.
ANDS – ANA975 for HCV placed on hold 6/26/06 due to preclinical safety issue; human trials expected to resume at end of 2H07 following FDA analysis of animal tox study.
ANDS – ANA380 in HBV: phase-2b to begin “sometime in 2007.”
ANOR / AOM.TO – pivotal AMD3100 results any day.
ASPM – Interim data from BRITE trial in depression: scientific conference in 2Q07.
BMY – Plavix trial begins 1/22/07.
BMY – Erbitux: see IMCL.
BOMSF -reporting pivotal MBP8298 results 2 years roughly
CEPH – Nuvigil for EDS approvable letter received 4/30/06; on 12/7/06, FDA said it was still studying one case of suspected SJS in Sparlon data set.
CLSC - Two phase 3 Trials 1600-2000 patients to complete in calendar Q4 with public " top line data" on results anticipated for calendar Q1 07. This is a 10 week trial.
COLY – Phase-3 PF-3512676 in NSCLC (by PFE): late 2007 or 2008 (2 trials).
COR – Go/no-go decision on CX-717: April/May 2007 following FDA review of the tox report now in preparation by COR’s CRO. (FDA clinical hold was partially lifted 10/9/06.)
CORT – Phase-3 trials of Corlux for psychotic major depression: ‘06’ trial results any day. (The first phase-3 trial called ’07’ reported failed results on 8/25/06; the 2nd phase-3 trial called ‘09’ reported failed results 9/29/06).
CRME - IV RSD1235 NDA refiled, FDA decision likely 4th qtr/07.
CVTX - Ranexa MERLIN data at ACC March 24-27, 2007.
CYT.TO - Initiated pivotal A-fib trial Oct/06. Results timing, will update when company provides timeline.
CYPB – Phase-3 Milnacipran in fibromyalgia, second phase-3 results: mid 2007 (#msg-9132392).
DDSS (formerly LBPFF) – Response to and appeal of Tramadol approvable letter submitted 12/20/06.
DNA – Avastin in breast cancer: FDA requested additional data confirmation on 9/11/06; resubmission by DNA pending.
DNDN – Provenge BLA: advisory panel expected in March 2007; PDUFA date mid-May 2007.
DNDN – 9902b study: enrollment complete in 2007; interim data look 1H08.
FRX - Milnacipran in fibromyalgia: see CYPB.
GILD – Viread for HBV: phase-3 results 4Q07, NDA (if successful) 1H08.
GILD – GS9190 for HCV: start phase-1 any day.
GPCB – Satraplatin SPARC trial: final overall survival: fall 2007. (The trial hit the primary PFS endpoint on 9/24/06; interim OS look announced on 6/8/06 failed to meet threshold for unblinding.)
GTCB – ATryn EU launch for HD: June, 2007.
GTCB – ATryn DIC program in EU: start of ph-2 (by Leo Pharma) any day.
GTCB – ATryn ph-3 for HD in U.S.: complete enrollment 1H07, submit BLA 2H07.
GTCB – Merrimack MM-093 phase-2b in RA, phase-2 in psoriasis to be presented at EULAR in June 2007.
GTOP – Final MyVax results Dec 07.
IDIX – Tyzeka for HBV action date in EU, China: early 2007 (approved by FDA 10/25/06).
IDIX – Tyzeka phase-3 in decompensated liver disease: enrollment complete in 1Q07 (75% complete as of 9/27/06).
IDIX – NM283+ribavirin drug-interaction study: preliminary data at EASL.
IMCL – (See #msg-9218093 for selected Erbitux trials):
1) CRSYTAL trial in first-line CRC hit its PFS endpoint (announced 1/10/07); full data release at ASCO in June, 2007.
2) Erbitux in NSCLC. OS in 1st-line FLEX study: 2H07.
3) Erbitux in pancreatic cancer, SWOG trial: 1Q07.
ISA.TO - Begin European/Cdn pivotal psoriasis trials this qtr, begin U.S. pivotal psoriasis 07, complete enrollment in renal Phase IIb & also interim renal data 1st qtr 07.
ITMN – Phase-1 PK data for ITMN-191: 2H07.
JNJ: CoStar (CONR) data from U.S. pivotal trial: March 2007 at ACC
LBPFF – see DDSS
Merrimack: see GTCB
MS.TO - Complete enrollment in pivotal Secondary Progressive MS trial this year, possible interim results 2007, trial results in 2008.
Novocell – see SRDX
NRMX, NRM.TO – North American Alzhemed trial complete Jan 07, results to follow. European Alzhemed trial complete 1H08 (?). Kiacta (Fibrillex) received an approvable letter on 8/11/06.
NRPH – NRP104 in pediatric ADHD: approvable letter 10/6/06; full approval pending DEA scheduling.
NVS – Galvus PDUFA date late Feb 2007.
NVS – Tekturna PDUFA date mid Mar 2007.
NVS – Tifacogin: enrollment complete 1H07 (#msg-15157973).
PHRM – See GPCB.
PPHM - Bavituximab phase 1B HCV; four doses monotherapy over 14 days, followed for 12 weeks post-therapy, in previous non-responders/relapsers. Patient enrollment completed Oct 24, trial results due 1Q 07.
PPHM - solid tumor 8-week chemo & Bavituximab combination therapy, info due 1Q '07.
RPRX
Proellex
*Uterine Fibroids Phase 2 (U.S.) Full Phase 2 data (mid-2007)
*One year extension data (4Q2007)
*Initiate pivotal trials (YE2007)
*Endometriosis Phase 1/2 (Europe) Full Phase 1/2 data (3Q2007)
*Initiate U.S. Phase 2 (mid-2007)
Androxal
*Male Secondary Hypogonadism Non-pivotal Phase 3 (U.S.) Full non-pivotal Phase 3 data (3Q2007)
*Initiate first pivotal Phase 3 (around YE2007)
SGP – Ph-2 data for SCH 503034 in HCV: 2H07
SNY – Acomplia PDUFA date: 4/26/07.
SNY – Plavix litigation: trial begins 1/22/07.
Speedel – See NVS.
SPPI – See GPCB.
SRDX - Novocell phase-1/2 trial in type-1 diabetes: late summer 2007 (enrollment complete 8/30/06).
TH.TO -Begin confirmatory TH9507 HIV Associated Lipodystropy trial 1st qtr/07
VRTX – PROVE-1/PROVE-2/PROVE-3 timetable: see #msg-12267294
YMI – AeroLEF final results any day (interim results announced on 9/27/06 failed to meet threshold).
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Similar to yours, Henry. It was an incremental positive. I think that of the remaining data issues that have not yet been released, the biggest potential positive for the Provenge BLA would be the 9902A cause-specific mortality data. If it's as good or almost as good as the CSM data for 9901, then 9902A becomes much more supportive in my view, and probably from the view of the FDA biostatisticians as well...but you can bet they would go over it with a fine-toothed comb.
I'm hoping that if the company has three or four presenters of the data, they would be Small, Petrylak, Urdal, and Provost.
re HEB: LOL! I didn't know that an "orphan drug product" that treats chronic fatigue syndrome (CFS) could be applied to an "orphan drug indication" with one million sufferers. Come on Dew, don't be so hard on them. Perhaps HEB isn't aware of the FDA's upper limit on the number of sufferers of a condition that would qualify it as an orphan indication. You can't blame the company for not knowing. After all, they've only been in the business for 20 years or so.
HEB: <<HEB gets my vote because I have personal knowledge of the company’s dealings that I don’t have with INGN. A few years ago, HEB offered free Ampligen in return for taping an infomercial touting Ampligen as a miracle cure for various ailments. This is a level that few companies I know have stooped to.>>
LOL! The old-fashioned elixir salesmen of the Wild West have been reincarnated. That's too funny...I wonder if HEB will end up in a pile of horse manure like the salesman in The Outlaw Josey Wales...
re INGN: Dew, David, and all--which do you think is the bigger scam, INGN or HEB? Sorry, but BPUR is not an acceptable answer, as it has already been elevated to the Biotech Scam Hall of Fame.
INGN story: Why Keeping Money in Introgen is a Fool's Game
Posted on Feb 20th, 2007 with stocks: INGN
Kevin McNamara submits: A recent article in the Street.com about Introgen (INGN) and its lead drug candidate, Advexin, focused on a tumor-like mass of evidence demonstrating the apparent worthlessness of Advexin’s clinical trial data and by implication the company itself. The article also peripherally addresses Introgen’s management team.
In many regards, however, this management team is more problematic than Advexin itself. Unfortunately, the pursuit of absurd science by biotech is not a crime. Nonetheless, one has to wonder how a company with two completely dead phase 3 trials that have not enrolled a single patient for the last several years is spending $20 million per year on R&D. In fact, it is inconceivable that the studies referenced in the company’s almost-daily press releases referencing preclinical data are sufficient to burn this amount of capital.
So where’s it going? No one knows.
As mentioned in the article, Introgen appears to have a fiercely dedicated following. While this is laudable in its own right, the absence of institutional involvement on the long side of the Introgen trade should cause a great deal of concern. Small investors can rest assured that the institutions that are short know more than them because that’s their job. And while there are large institutions on the long side, the largest (Fidelity) doesn’t count. Fidelity owns everything and their INGN position represents 0.0007% of their entire portfolio. The bottom line is that it is not a question of if individual investors are going to lose 90% of their investment; it’s a question of when!
In return for waiting out INGN’s and/or Advexin’s death, the stock does nothing as evidenced by investors’ gross return of 0% in five years and the accompanying dilution that comes like clockwork after each incremental $25 million is burned. While not losing a lot of money investing in biotech is a good thing, the number of alternative investments in the sector suggests that leaving money in INGN is a fool’s game.
And Finally . . . The “Data”.
The dead Advexin pivotal monotherapy trial in recurrent, refractory, unresectable SCCHN (‘301) is an approximately 240 patient trial comparing Advexin to standard chemotherapy (methotrexate) after surgery and radiation have been ineffective (the dose in this trial will replicate the high-dose in one of three phase 2 trials). The primary endpoint is survival and the secondary endpoint is time to progression. To date, there has been no disclosure whatsoever with regard to the phase 2 program related to time to progression although the measure was a secondary endpoint in two of the three phase 2 trials and appears to be the only surrogate endpoint viable for the accelerated approval. The ‘301 trial started enrolling around May 2001 and evidence strongly suggests that the trial stopped enrolling a long time ago.
The dead Advexin combination trial (‘302) is an approximately 255 patient trial (although it was originally described as a 288-patient trial) comparing Advexin in combination with standard chemotherapy (cisplatin+5Fu) to standard chemotherapy alone in chemotherapy naïve patients. The primary endpoint is time to progression and the secondary endpoint is survival. The 495-patient phase 3 pivotal trials (expected enrollment as of 5+ years ago) were designed based in part on an analysis of a subset of patients in one of three phase 2 trials (referred to as T-201 – the “high dose” phase 2 trial). This is what phase 2 trials are for.
In contrast, Introgen now believes they are suitable for actual registration. The subset was comprised of the first 88 patients treated and evaluated (107 were treated in total). Reported median survival time for a subset of this subset of 88 patients was 7.5 months (220 days). The subset is apparently characterized primarily as those with refractory disease and a tumor size threshold of <7.5cm but the number of patients in the subset has not been disclosed and the exact characteristics of the subset have not been adequately described for reasons that are entirely unclear to us (INGN, however, cites patent concerns).
This subset apparently didn’t respond as expected so the new subsets are based on some undisclosed biomarker. IINGN has reported that this 7.5 month MST compares to an investigator-estimated expected MST of 4 months, citing an 88% benefit in the subgroup of the subgroup evaluated. As way of comparison, Imclone’s Erbitux has been studied extensively in SCCHN. A phase 2 trial in platinum-refractory recurrent disease demonstrated an MST of 5.5 months as monotherapy as compared to the above-noted historical controls in platinum refractory patients of 3.5 months.
The latter is still inferior to the results reported by Introgen but were based on a prospectively designed trial as opposed to being the result of combing through data until something of interest was found. Besides this trial, two other trials of Erbitux in combination with platinum compounds in platinum-refractory SCCHN patients reported objective responses in 12% and 15% of patients and an MST of approximately 6 months.
Iressa has also been studied in refractory recurrent SCCHN. In a phase 2 study, median survival was extended over the expected 6 months for that patient population to a reported 11 months. As noted, INGN designed and initiated its pivotal phase 3 trials in part based on data scoured from the above referenced subset of 88 patients from the T-201 trial. As things stand today, the T-201 trial is retrospectively defined subset of the three-trial phase 2 program to the extent that INGN has regularly referred to the aggregate data from the phase 2 program as essentially one registration trial in terms of its data analysis. INGN has been cherry-picking this data in order to determine what questions to ask based on the answers generated and surprisingly some of the most important answers, specifically those related to ORR, have actually changed.
The primary efficacy measure in two of the phase 2 trials (T-201 and T-202) was objective response rate yet ORR for the intent-to-treat group has been reported for neither of these trials (it was not a primary efficacy variable in the third trial (T-207). Nevertheless, INGN reported in March 2004 that the “primary endpoint results” from the three phase 2 trials confirm its “previously reported” findings regarding the activity of Advexin. The primary endpoint results that INGN “previously reported” and appears to be referring to (specifically, tumor growth control) have not been previously reported by Introgen from any of these three phase 2 trials except for preliminary analyses and/or selected post hoc subgroups – there has been no disclosure, ever, with regard to intent to treat populations. Having said that, a National Cancer Institute website states that the objective response rate in the three phase 2 trials
was 4% and stable disease was observed in 22% of patients (145 evaluable patients).
This is pathetic and is consistent with the 8% ORR observed in the first 88 patients treated and evaluable in the T-201 trial and the 25% stable disease rate reported for these patients. However, it is inconsistent with the 15% ORR that INGN has previously reported for a select group of unidentified patients that Advexin luckily appeared to benefit that has recently and inexplicably been increased to 20% and even at the new, higher figure is inferior to the reported 23% ORR in a prospectively designed Erbitux phase 3 trial that was analyzed on the basis of a prespecified statistical plan on an intent-to-treat or prespecified per protocol basis.
Perhaps “inexplicably” is an inaccurate description inasmuch as INGN management declared on a May 10, 2005 conference call that the “analysis” which resulted in an increase in the ORR to 20% from 15% is something that they are “conducting” and “defining” and the figure is “approximate”. There is clearly a possibility that when INGN is done “conducting” and “defining” that analysis that ORR will be even higher.
Also of interest is the fact that tumor growth control was not the primary endpoint of any of the three phase 2 trials. In T-201 and T-202, ORR of the treated lesions was the primary endpoint (the difference appears to be that that tumor growth control also incorporates stable disease). As for T-207, which was a biodistribution and transmission study, no data has been reported other than the MST of an unidentified subgroup of unidentified scope that received chemotherapy after the fact and likely received it outside of the scope of the protocol.
MST's for both T-201 and T-202 were also reported for this de facto patient population in March 2004. In something I have never seen in the annals of reporting clinical trial results, INGN refers to the already preposterous interpretation of the data from these three trials as a “multi-center, multi-national, analysis” as if the global scope of the analysis validates the selective and highly biased post hoc conclusions. Aside from the fact that tumor growth control was not the primary objective of these studies, the clinical import of these studies based on “tumor growth control” is particularly suspicious and the endpoint is not an approvable one anyway, particularly on an accelerated basis.
In fact, the protocol summary for T-301 itself speaks at length about the questionable correlation between clinical benefit and “stable disease” (i.e., tumor growth control). Although the summary does not entirely dismiss the notion that tumor growth control is indicative of clinical benefit, it clearly states that traditional tumor size measurements are inefficient in reflecting anti-tumor activity and refers to the measure as a “not fully validated surrogate for clinical benefit” for the following reasons: (a) measurements do not consistently reproduce the actual tumor changes and (b) tumor size measurements [in the Advexin phase 2 trials] were inaccurate because of the nature of the tumor and the fact that prior surgical resection and irradiation sequelae commonly rendered tumor limits imprecise.
In other words, the 59% tumor growth control rate evidenced in the combined phase 2 trials that will apparently be used in part as support for accelerated approval based on its surrogacy for clinical benefit were dismissed by whoever wrote the T-301 protocol sometime during the summer of 1999. Moreover, the 59% tumor growth control rate cited appears refer!
s to treated and responsive lesions as opposed to treated patients.
The company’s 2002 10-K reveals that the preliminary analysis of 88 patients in the T-201 included patients who had multiple tumors treated. If efficacy was measured as the number of patients responding the figure appears to be 25%. When efficacy was measured as the number of patients who had at least one tumor responding the figure appears to be twice as large at 60%. Again, the company appears to have created the opportunity to take multiple shots on goal on a de facto basis. It is not unreasonable to ask what the clinical value of a patient who has one tumor responding while one or more of the patient’s other tumors don’t respond?
The answer is zero.In an FDA review of an experimental drug for SCCHN in 2001 (a formulation of collagen, cisplatin, and epinephrine in the form of a gel directly injected in head and neck lesions) the FDA noted the following:
“Although a lesion may decrease in size or completely disappear, clinical benefit from such shrinkage cannot necessarily be assumed. The findings have implications for future trials of local therapy in the refractory/relapsed head and neck squamous cell carcinoma setting.”
This comment was made notwithstanding the fact that the FDA’s preliminary analysis of the data indicated that objective response rates would ultimately work out to be between 19% and 27% in one of the phase 3 trials and 16% to 21% in the other phase 3 trial. These figures were actually the result of the FDA’s dissection of the sponsor’s reported response rates which were 34% and 25%, respectively, for each trial compared to the ranges above, which is a type of dissection I suspect could likewise be applied to both the phase 2 and phase 3 Advexin data.
Nonetheless, even the dissected and reduced figures cited above are significantly higher th!
an the 10% ORR claimed for Advexin in a presentation at the 2004 AACR of a meta-analysis and higher than both the 15% claimed by the company in a 2004 press release describing a subset of the phase 2 trial and the more recently enhanced 20% ORR. At the risk over-analyzing the FDA’s position on clinical benefit, I think the following comments from the FDA on this NDA are critical:
“In the mid-1990s, FDA and the Applicant held numerous meetings to discuss how one might design a trial to document the clinical benefit associated with local treatment of incurable head and neck cancer. FDA's position was that shrinkage of tumors from local injection of chemotherapy was not sufficient evidence of clinical benefit. Any treatment, including local treatment, was likely to produce some side effects, and nobody had proved that temporary shrinking of head and neck cancer yielded any benefit that the patient could perceive. One of the difficulties encountered was that head and neck cancer patients suffer many different problems, so that it would be impossible to accrue enough patients to evaluate treatment of each problem separately.”
The likelihood of FDA approval based on this data or even the acceptance of a rolling BLA based on the data verge on the ludicrous. In another historical oddity, INGN announced that it had submitted the first portion of what it intends to be a rolling BLA in December 2004 even though approval of the company’s request for a rolling BLA has not been granted by the FDA. There have been suggestions that INGN has dredged enough data from the phase 2 studies to isolate a link between response rate and survival and between stable disease and survival. There is not a shred of evidence that this is the case and the FDA comments cited above argue against this possibility.
INGN frequently cites the Code of Federal Regulations when describing the potential regulatory pathway available for Advexin citing, for example, Subpart E (21 CFR 601.31), which permits accelerated approval based on drugs and biologics that meet unmet medical needs and based upon surrogate endpoints that are reasonably likely to demonstrate clinical benefit. What INGN doesn’t mention is the requirement under Subpart E that marketing approval even under these relaxed standards is on the basis of adequate and well-controlled clinical trials establishing an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit. Regardless of whether a surrogate endpoint is deemed sufficient for approval of a drug or biologic, the FDA always operates under the premise that studies relied on to support effectiveness meet the requirements for adequate and well-controlled studies in 21 CFR 314.126, regardless of whether those studies are the basis for approval on a surrogate endpoint.
The FDA further notes that reliance on substantiation of efficacy from related trial data leaves little room for study imperfections or non-supportive information and the results must always reflect a clearly established prior hypothesis documented in a protocol. Investors must ask themselves whether the Advexin phase 2 trials meet this standard. They don’t.
These regulations are no secret in the world of biotech but may be instructive for investors to also consider INGN’s strategy in light of ICH guidelines relating to principles for clinical trials. These principles are supportive of the view that the likelihood of a BLA approval based on the phase 2 program for Advexin is unlikely. Ironically, a number of these comments were quoted in 2001 by FDA reviewers of Matrix Pharmaceutical’s NDA for approval of IntraDose for squamous cell carcinoma of the head and neck, which was supported by two pivotal trials and two phase 2 trials.
As noted above, IntraDose was a combination of two already approved drugs, cisplatin and epinephrine, and cisplatin has well-documented cytotoxic activity in SCCHN. The drug was nonetheless rejected partially due to safety issues but primarily due to efficacy issues and questionable trial design and endpoints. So ask yourself: What is the hypothesis upon which the Advexin BLA is based? It’s not pre-defined inasmuch as INGN management openly stated in its recent May 2005 conference call that “part of the value of these subpopulation analyses of course is to better educate us on asking the most appropriate question as databases are open.” INGN itself has indicated that it finds value in the opportunity to basically collect data first and ask questions later. The only p-value ever mentioned in reference to the phase 2 programs relates to the difference in MST of the high-dose and low-dose trials.
Aside from the fact that these trials were not distinct, the p-value supports the null hypothesis – i.e., there is no effect. The meta-analysis of the three phase 2 trials, notwithstanding the fact that it was a “multi-national analysis” did not have its own prospectively written protocol. INGN’s comments confirm this fact inasmuch as they frequently refer to evolving analyses. Aside from these guidelines, the FDA also noted in the above-referenced NDA review that it had told the sponsor that “Clinical benefit and response analyses should be based on the intent to treat population with all other analyses playing a supportive role, subset analysis for patients who are considered incurable with surgery should be done, and prior therapies must be extensively described to document refractoriness of disease.” Pivotal Trial Enrollment INGN has not revealed and has indicated its intention not to reveal in the future the status of enrollment in either of the pivotal phase 3 trials, allegedly due to competitive concerns.
I do not buy into this argument and have heard it many times in the past from early stage biotech companies. The T-301 monotherapy trial was announced in March 2000 while the intent to initiate the T-302 trial was announced in late July 2002. At the time, Introgen announced that expected completion of enrollment in both trials would occur simultaneously at the end of 2003. Introgen also stated that interim analyses would be conducted for both trials at the 50% accrual point.
However, other comments have suggested that the ‘301 trial could be analyzed on an interim basis at 109 deaths, i.e., the interim look would be event driven as opposed to accrual driven. No interim data has been announced or released to date raising the possibility that neither trial has reached 50% accrual. In fact, in June 2004 INGN disclosed that it expected the interim analysis triggering event for the T-301 trial to occur over the next year – the next year is now here and there is no word on an interim analysis.
In other words, the ‘301 trial, even though commencement was announced in March 2000, has likely not reached the 50% mark (this assumption is fairly safe given MST’s of 7.5 months seen in the phase 2 trials in an apparently very tiny subset of patients). The facts appear consistent with all attempts to estimate patient accrual and consistent with the company’s late 2004 decision to file based on phase 2 data. While it is not possible to accurately back into the enrollment status in the SCCHN pivotal trials anyone’s best efforts to do so raise disturbing possibilities.
http://biotech.seekingalpha.com/article/27343
INGN 1-yr chart
Didn't NRPH negotiate a partnership deal with Shire that gave NRPH something like 60% or 70% of Vyvanse sales? I seem to remember a contact of mine stating this several months ago.
re ASPV: It's a compelling value, but I believe the analysts and larger institutions are playing the wait to see game about whether or not mgmt can competently in-license another product to help off-set the upcoming revenue hit from the patent expiration.