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<<In addition to always having the hottest docs at any conference, the Brazilians are the world leaders in creative Botox uses.>>
Outrageous statement...need photographic evidence
House passes PDUFA renewal. There is a provision in the House version that reduces the number of conflict-of-interest waivers that are granted to advisory panel members. The article mentions yesterday's march as not being successful in getting what it wanted on the experimental drug for terminal diseases issue, but doesn't mention that the other goal for the march was getting the number of COI waivers reduced.
#msg-23015568
re-Lucentis:
Gee, I'm not seeing any separation there
TheStreet.com reports AAPL will introduce 3G iPhone in Q1 2008, with chips from Broadcom and TriQuint.
Apple to Introduce Faster iPhone Next Year
By Scott Moritz
Senior Writer
9/17/2007 2:37 PM EDT
Apple (AAPL - Cramer's Take - Stockpickr) will deliver the next version of the iPhone early next year, TheStreet.com has learned.
A faster third-generation, or 3G, iPhone will be available sometime in the first quarter, say people familiar with the production plans. The new iPhone should help quiet critics who were unimpressed by the 2.5G EDGE technology the first version used.
http://www.thestreet.com/s/apple-to-introduce-faster-iphone-next-year/newsanalysis/techtelecom/10379...
OT-I debated for a few minutes about linking to this off-topic subject, but it was just too hucking filarious that I couldn't resist. The groups in these two links make up a significant portion of the anti-science, anti-evolution, anti-intellectual, anti-biotechnology crowd that has been dragging our country down.
http://tinyurl.com/2cgyhu
Reading the first post reminded me of another hilarious article I read a few months ago. All I had to do to find that link was do a google search for "Giant Moron Magnet." As a noted comedian/political commentator has commented about this Giant Moron Magnet in Kentucky... "putting saddles on dinosaurs? We thought that was hilarious back when we were kids in the 1960s, watching the Flintstones!" Yeah, Noah was able to fit every dinosaur on the Ark, because he took baby dinosaurs...bwahahahahaha!
http://theopinionmill.wordpress.com/2007/05/19/the-moron-magnet/
Discussion with DNDN CFO, from plotinus4me over at I-Village:
http://www1.investorvillage.com/smbd.asp?mb=971&pt=msg&mn=155701
Msg: 155701 of 155704 9/14/2007 1:34:45 AM Recs: 6 Sentiment: Strong Buy
By: plotinus4me Send PM Profile Ignore Recommend Add To Favorites
Thoughts on recent posts and discussion with Greg Schiffman 9/13/07
On every MB for every stock, you will inevitably find posters who are down on the management. It doesn't matter what industry, it doesn't matter whether the stock is up or down (although one finds these malcontents most often with stocks whose price has fallen or whose price hasn't gone up much over a period of time), there just seem to be dissatisfaction with the CEO, CFO, and/or IR. Check it out for yourself. I follow a number of stocks and am always looking for new ones to invest in, and sure enough there are the posters with a grievance.
DNDN is saddled with its detractors. Most love the science but can't stand Dr. Gold, Monique (who has now left the company, sadly for me), and there have been others. I haven't posted much since May 9 as there really hasn't been much to discuss. I have felt that management had done what they could to get Provenge approved and are now doing what they can, as fast as they can, to go for the approval again. After the positive Panel, it has been clear to me as it has been to many others, the fault for Provenge not getting approved could be laid to the CDER/ODAC side of the FDA. Possibly there was some complicity at CBER and possibly on a higher level, but the letters of Scher, Hussain, and Flemming were clear where the initial problem lay.
Now some think that DNDN did a poor job at the Panel meeting, but the results were overwhelmingly positive, so the DNDN people who presented there along with the BLA details, were good enough. Yes, it needed a phrase revision re the efficacy, but that was resolved.
Maybe someone else posting on the MB could have done better over the years or after the FDA decision, but I doubt it. I have been an avid reader of the posts over the last @3 years on Yahoo, IV and IHub. There have been some terrific posts by some really knowledgible people. But I don't think I have seen anyone's posts who could have done as good a job as the DNDN management breaking new ground re the immunotherapy field with a revolutionary new concept, adapting to changes in the way patients responded, and working with the FDA to provide a compatible BLA that should have been approved, set up a viable 157,000 sq. ft. facility in about one year for the production of Provenge, get the antigen supply approved and on stream with Diosynth, get sufficient funding (albeit with a rather ineffective approach- this now seems to have improved with the new CFO), get the BLA sent to the FDA with the first computerized submission of any company, get the CMC and BLA reviewed with priority, and then the positive Panel along with presentations at conferences and publications, and so many other things.
Frankly, anyone long this stock over the last 3 years should be looking at management as doing a very good job versus the lousy and perfidious job done by the FDA. I have great admiration for KDD, AMMASS, Yarbonero/ Mr. Serious, cben, walldiver, rancherho, ocyan, clarkster, and all of the many people who have spent incredible hours to refute the Scher, Hussain, Pazdur, Cancer Letter, analysts, and others initially after the May 9 decision and now with the demonstrations and the lawsuit against the FDA, et.al.
I have given how I feel about this and there are many, I'm sure, who will disagree with me. Such is life.
Now I am going to tell you of my discussion with DNDN's CFO Greg Schiffman (GS) on Thurs., Sept 13, 2007.
I met with GS briefly, along with some others, at the ASM. I knew he wouldn't remember me by name, but he remembered that I had used the word "Pazdurized" to reflect my disgust of the one man I felt had done so much to hurt a new field of cancer research as well as subvert an FDA approval for a drug which would helped many men with PC. He did remember that part.
Below are my impressions and understandings of my discussion with GS. As I was hurriedly writing down notes of our discussion, it is hoped that my notes are accurate. I have tried to put the discussion in a way that is more readible. Please understand that GS was very detailed in his answers and I have tried to capture the key points and substance of his answers. I hope I have not misrepresented his points in any way.
Ques: Why hasn't DNDN set up operations in a foreign country that has easier entry to providing Provenge to patients? For example, one that would recognize that the safety/efficacy re 9901/9902a and the Panel recommendation should have been sufficient for FDA approval. A smaller, NJ type plant could be established, possibly through an already established, approved facility. Presumably there would be leukopharesis facilities available in the area or easily set up. Countries that I suggested were: Dubai (as per Casey), Israel, Norway. and Thailand. There shouldn't be any problem with the FDA as companies are doing this all of the time.
Ans: DNDN had priorities. First, we had to find out what the FDA wanted from us re the BLA and then the trial data. This had to be determined and this has been done. Secondly, the plan of action had to be commensurate with our finances. Now that we have resolved these issues, we are able to look at other possibilities.
It is important to understand that many countries determine whether they will approve certain drugs based on U.S. and European approval. There are a number who do not but there may be certain qualifications to be considered. DNDN is evaluating a wide range of options and there is nothing specific at this time. But DNDN has been active in this area.
Ques: When should we hear news on 9902B full enrollment?
Ans: At this time, DNDN is no longer accepting applications for pre-enrollment. Enrollment is before the first infusion is given (either placebo or shot).
DNDN will announce when there is full enrollment. Guidance is for the 4th quarter of 2007.
Ques: How many employees are there at this time and I noticed that there are some new job openings?
Ans: There are about 200 employees and the new hires are based on specific needs of the company.
Ques: Will there be an announcment when the NJ plant 483 issues are resolved with the FDA? Any time frame? How could they be doing Provenge for 9902b if there was an FDA issue?
Before I go into the ans. on this, I want to say I have tried to understand and write the subtleties of GS's answer as best as I can. There are some on this MB that are far more knowledgible about this subject than I am and it might be helpful for these people to contact DNDN to confirm or amplify my notes on this.
Ans: When the NJ plant was inspected re the CMC, the FDA issued some feedback, ie., 483s. The 483s are not the same as the CMC. The person who oversaw the inspections was the one who was available to discuss the CMC and the 483 issues prior to (or during?) the Panel meeting. The CMC was available at the time of the Panel (AC). There were no issues that arose to a point which was "rate limiting" (AND THIS IS THE IMPORTANT POINT) and there was nothing material in the 483s that would have affected getting product approval. The CMC and the 483 issues were done at different times, both were part of the "approvable" letter. Apparently there needed to be some further discussion with the FDA on these issues at the time (as per my understanding).
Follow-on question: How could the NJ plant produce Provenge for the 9902B trial if there was a problem with the FDA with regard to the facilities or re the CMC?
Ans: There was nothing re the 483s to restrict doing Provenge for the 9902B trial. However, the plant could not produce Provenge for commercial quantities.
Follow-on question: When will the 483 issues be resolved, ie., when will there be a "pre-approved re-inspection"?
Ans: The FDA itself will give no formal documentation until the application is updated. There will be another inspection and the results will be part of the re-submission of the amended BLA filing.
Ques: Is Dr. Small still working with DNDN and in what capacity? Who is the lead researcher re 9902B?
Ans: Dr. Small's center is one of many re 9902B. He was the lead researcher on 9901. He is not the principal researcher on 9902B. He could not say who was. The main point is that Dr. Small is still associated with Provenge (which is what Monique told me at the ASM and which I reported on the MB a while ago).
Ques: What about finding a partner for Neuvenge which has several possible cancers that could be addressed?
Ans: Most potential partners are looking for advanced Phase trial results. Their first choice would be Provenge. He had no specific comments at this time whether there was any interest in Neuvenge re partnerships or with Provenge. They have had a number of prospects which they are evaluating was my understanding.
Ques: Could he comment on the efforts made re the law suit or the demonstrations?
Ans: GS could only answer regarding advocacy groups in general. He could understand their frustration. He and DNDN could not comment in any way. However, given the time frame of the mid 2nd half of 2008 when the interim look should occur, he wasn't sure whether they could speed up any time re FDA consideration or not. Basically, DNDN can't comment on such matters and I am sure everyone should be able to understand why they cannot.
Conclusions:
I found GS to be open, informative, and really helpful in my seeing the difficulties management has been faced with the "approvable" decision by the FDA. I believe that they have not been issuing a lot of press releases as their efforts have been directed toward getting the 9902B trial enrolled, getting the financing, resolving FDA issues, evaluating partnership and foreign opportunities, and moving forward as quickly as possible to make DNDN a viable player in the cancer arena.
For myself, I have been in and out of DNDN since May 9 on a trading basis. I am currently about 2/3rds the position I had before 5/9. Barring bad news or a technical aberration to the downside, I am looking to build my position. While I do not hold out much hope that the FDA will see the light and give a conditional approval to Provenge, I am hoping for DNDN to look outside the U.S. for additional opportunities.
<<Just another IV conspiracy theory – Dr. Small abandoning Provenge in favor of GVAX and his MIA on 3/29.>>
OMG that's too funny. Dr. Small's UCSF trial center has been one of the big centers for the GVAX Phase 3 trials for the past three years. He might even be the lead investigator for VITAL-1 or VITAL-2. The DNDN longs have known this for three years. I guess there are a bunch of newbies in the stock. The next thing we'll find out is that I-Village is going after other Provenge advocates like Higano, Berger, and Vogelzsang for running trials featuring other HRPC treatments, or saying that combo trials in HRPC using Taxotere in the control arm are being sponsored by SNY...lol
That's nice...hadn't heard from him re Provenge after his flight to the AC meeting was cancelled. Is there some sort of controversy re Small?
Immtech does have Phase 2 malaria programs for both prophylaxis and treatment, and a Phase 3 program for sleeping sickness. I would imagine that the US military may be a bulk buyer of any effective prophylaxes/treatments for tropical diseases, and the addition of General Clark is for his military connections. Might not be as far-fetched as it appears on the surface.
Then this is an entirely new position. If so, it appears that more than one factor caused the price spike today. Some big firm or firms obviously got wind of BNP's position before the electronic filing went through. Also, someone emailed me that Bloomberg reported the Provenge BLA was just granted fast-track status, which is ridiculous but you never know with some of these newswires. Fast-track news is always a price spiker for the mo-mo traders in development-stage biotechs, even though it doesn't really mean anything and isn't nearly as important as priority review. The current BLA for Provenge was originally granted fast-track status in late 2005, and priority review status in January 2007. Lastly, I wonder what's going on with today's registry of shares...maybe it has something to do with the already-filed convertible deal a few months ago.
The BNP Paribas hedge fund picked up shares over the last couple weeks. It's been reported that it's an entirely new position, but I haven't checked the fund's holdings to see if they had any DNDN shares on 6/30.
re today's price spike: DNDN filed an S-3 with the SEC early this morning. Company appears to be registering securities. Maybe this it's related to the price spike.
Bailing out those with the short position did not play into the FDA's decision making. CBER and Von E caved from the pressure applied by OOD and many in the oncology community. End of story.
Have to agree. Until proven otherwise, take anything CTIC does with a grain of salt.
Nope...from the briefing docs, there were 179 pts on Feb 6, 2006. I'm estimating that there were 99 in Feb 2005. Just an educated guess.
My comments a few days ago re 9902B recruiting no longer:
#msg-22535634
They've tested it in solid tumors, which included breast and ovarian, and saw efficacy...but I've never seen the individual breakdown in those trials. The company is still talking about possibly testing it in ovarian. They should run a small Ph2 trial in ovarian before committing to a Phase 3.
<<Are there any thoughts on Dendreon's pursuit of an International ROW partner, not just for Provenge, but for Neuvenge?>>
For Provenge, a ROW deal could happen anytime, but judging from past habit, I think mgmt will wait until 9902B interim results are in before finalizing any deal. As for Neuvenge, I think its future (finally, after bi***ing about it for two years) will be in HER2/Neu positive ovarian cancer, for which it would be an orphan indication and thus no need to partner in USA. The same orphan indication in the EU would be ideal for DNDN to establish its own specialty sales force there, and go 50-50 on sales & expenses with its ROW partner in Europe, plus milestones and upfront cash. This EU partnering scenario would be most likely to happen if Provenge has already been approved in USA.
<<Is there really a serious suitor for Provenge that DNDN would consider?>>
Yes, I'm sure there is...but the most desirable suitors are probably taking a wait and see attitude on 9902B, and are probably not offering lucrative enough terms at the moment.
<<And for Neuvenge, since it is temporary shelved due to lack of funding, would a large pharma not be interested in a potential breakthrough for breast cancer?>>
IMO, Neuvenge for breast cancer is dead for the forseeable future, i.e. the next five years. Herceptin for HER2/neu+ MBC is already a near blockbuster, while Herceptin as an adjuvant in frontline breast w/chemo will be huge, and probably eventually reduce the size of the HER2/neu+ MBC market. It would take years to enroll patients in a Phase 3 Neuvenge trial in MBC, as it would likely have to be for 2nd line patients refractory to Herceptin, a shrinking market because of the Herceptin use as an adjuvant after surgery.
Ovarian is the low-hanging fruit...it could be an orphan indication because ovarian isn't a huge market, and only 1/4 of these women test positive for the HER2/neu gene. So, the pivotal trial wouldn't have to be that large, and might even be single-arm (though I doubt the last part). Neuvenge as an orphan treatment would have very little competition, and DNDN could charge a boatload for the treatment (a lot more than the Provenge $35-45K).
Well, it looks like they're no longer recruiting patients, so enrollment completion of 9902B IMPACT will probably be announced sometime in the next six weeks, when the last patient is randomized. I would imagine that they will probably go a little bit over the target of 500 patients, as there is a good chance all eligible patients who are currently in the queue will be counted. They might even announce it when the 500th patient has been randomized, and then say that enrollment won't be completed until the final patients in the queue get randomized.
It appears that the likeliest # of events that trigger the interim unblinding is 180, a logical number as it's been announced that 360 events will trigger the final unblinding. I'd prefer 200 for the interim, as there will be a lot of late enrollees still alive in the control arm who will have to be censored, thus hurting the p value.
The company stated recently that they expect the triggering event to occur in the middle of 2H 2008, meaning late Sept/early Oct. This probably gibes pretty well with what we know of the enrollment numbers, and the fact that the first ~150 patients were Gleason 7 or less:
Feb. 05 - 99 patients*
02/06/06 -179 pts
11/06/06 -294 pts
Mar. 07 - 400 pts
*assumption from Nicole Provost's Feb 2006 CTGTAC presentation
I'm not the best at valuing options. The SNUS options that I've picked up so far are the Sept 5 calls and the Oct 7.50 calls.
Looks like a monotherapy trial? I don't see any mention of a chemo combination. Also, it's for chemo-naive patients. It could enroll fairly quickly, as VITAL-1 has completed enrollment and IMPACT will have completed enrollment by November.
It's BSR_David
Biomund-sent you a PM on the other board eom
Mgmt did periodically give 9901 survival data updates. However, it was just ongoing followup, as the primary endpoint had already failed.
The DSMB will inform DNDN of the trial results, and I think mgmt will go over them pretty closely. If the trial continues, it will be because (1) the DSMB recommends it continue based on there being a chance of success at the final unblinding; and (2) the trial did not hit the interim alpha, or even the standard significant 0.05 p value. DNDN won't tell us anything if the company doesn't file for approval and the trial continues. None of the other biotechs have released the type of interim data in your post, so I highly doubt DNDN will.
Good points...it's hard for them to justify not allowing crossover, but this appears to have been more of an oncology group trial than a Genentech-sponsored trial, which could mean that Genentech wouldn't have been pressured by the FDA to include a crossover component. However, I would imagine that some control arm patients did cross over, nevertheless. YOU try to keep a vocal, motivated woman from receiving a life-saving or life-extending treatment. I certainly wouldn't want to...LOL.
All it would have taken would be 20 or 25 crossovers where Avastin showed efficacy to mess up the survival p value enough to miss stat sig. The 0.67 survival HR was from the original ASCO presentation in Spring 2005, while the 0.84 HR looks like it was from the Dec 05 San Antonio conference.
Well, DNDN mgmt is on the record that they expect the interim event trigger to occur in the middle of the second half of 2008...so I got time. I'm not expecting a partnership deal to be signed until then...unless DNDN gets blown away by an incredible offer, i.e. something like at least $100 million up front, $300mm in milestones, and 25% royalties on sales. But I don't think they can get an offer this generous until stat sig 9902B results come back, and also only if their ROW partner receives assurances from the EU that it doesn't have to run an additional successful trial beyond 9902B.
<<According to DNA, hardly anyone is actually being denied reimbursement for off-label Avastin.>>
One is one too many.
<<I don’t understand your point—what do the FDA’s actions on the sBLA have to do with the availability of Avastin in other countries?>>
I'm sure that there is at least one foreign country where Avastin approval has been delayed as a result of the Pazdur decision. FDA's stamp of approval goes a long way internationally. At least the EU has more common sense than Dr. P.
The survival HR at the interim was 0.67. The DSMB then halted the trial and offered Avastin to all of the control arm patients for compassionate/ethical reasons. After the Taxotere-only patients crossed over, the HR increased.
Steve, did you read the latest issue and its discussion of the interim? I hadn't been planning on getting back in with a large position prior to the interim data release...but now...
I consider ex-US lives to be as viable as US lives, in addition to those in the US with breast cancer who can't afford Avastin because their insurance companies won't pay for off-label use. I firmly believe that the middle and lower socioeconomic classes deserve access to effective lifesaving drugs like Avastin, and shouldn't be punished by some insurance companies for their comparative dearth of financial resources. So, I'm going to have to agree to disagree with you on this issue.
Zipjet, is this international company a privately-held company based in San Francisco, whose name starts with a B?
I'm saying that Pazdur is obsessed with methodology at the expense of clinical efficacy and benefit. He held up the Avastin sBLA to make a methodological point. He could have made his point while deciding to hold up approval of a different, less effective treatment (he often does). Adding Avastin for frontline metastatic breast cancer is not one of the lesser efficaceous treatments. A hazard ratio of 0.50 in the primary endpoint (Avastin doubled median time to progression), a similar HR in the secondary endpoint of PFS (again, almost a double at the median), and an HR of 0.67 in interim overall survival aren't marginal results. He's playing with people's lives here, and he doesn't give a flying fu...squirrel.
If I were an armchair psychologist, I would say that he took the MD Anderson beat-down far too personally, and that a lot of his stubbornness on this issue is due to his ego compensating for having to accept the less prestigious position at the FDA. However, I'm not an armchair psychologist, so I would never say that
I'm in favor of the lawsuit because it shines light on the issue. I would like to see Hussain and Scher testify to who asked them to write their letters to the FDA, and if those letters were actually written by the two good doctors. I'd also like to see how far financially Scher is tied into Proquest Investments. Then, I'd like to see exactly what role CDER/OOD had behind the scenes. Finally, I'd like to see what the CBER officials who made the decision have to say. I don't know if any of the latter will have to answer questions.
The lawsuit might also accomplish the task of keeping enough pressure on the FDA that it is forced to approve Provenge if the BLA is refiled after the interim 9902B results are released. Without this pressure, I could easily foresee Pazdur, Hussain, and Scher again fighting tooth and nail to keep it off the market, even with stat sig interim results.
That 1 in a million chance that you mentioned is off. I think there were 7 or 8 zeros in the p value, so it should be more like a 1 in 100 million or 1 in a billion that those Avastin Phase 3 results were due to chance. Amazing, isn't it...
Thanks for that. There is also an extremely important piece of positive news for the company that was revealed in BSR's latest issue. Can't discuss it as it's proprietary, but I would recommend all DNDN longs to purchase at least the anniversary issue that was published a few days ago, if not willing to subscribe.
That's good to know, especially if one is a DNDN long.
Yes, she knows how to play politics with Pazdur. I'm sure she has different reasons among friends. Let's face it, "standardizing the methodology for interpreting radiological scans across international lines" is a decent reason to hold up approval if p=0.03 or 0.04...but if it's a p value with eight zeroes to the right of the decimal point, then it's merely an exercise in methodology masturbation that has been ordered to satisfy one person's ego.
re DNA-Avastin submission for breast:
Yes, even though the ECOG reviewers and another set of independent reviewers have both determined from the scans that there is a significant clinical benefit (probably something like p=0.00000001 or better), an independent group of left-handed pygmies has not yet been consulted...so Dr. P will reluctantly decide to issue another complete response letter. Perhaps if there had been one more zero to the right of the decimal, he would have been convinced there is a clinical benefit.
Seriously, his decision last year to issue the CRL was far more pinheaded than his Provenge tantrum. IMO, it was the single most outrageous decision by the FDA in the past ten years.
Nice article on specialty pharma companies. It has some graphics that I don't know how to post here.
http://news.morningstar.com/articlenet/article.aspx?id=203879