Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
OT-ARXT
Yep, I used Mucinex DM. Worked like a charm. I also use pseudoephedrine as prophylaxis prior to every dive.
Whichever way this patent case turns out, Mucinex is the best cough suppressant I have ever taken. When I got sick on my recent trip to Asia and my head cold inevitably changed to a cough, the tablets I took once per day completely stopped my cough in its tracks. Normally I would have had several days of misery for which no OTC suppressant would have been more than marginally effective.
OT-Holy crap...looked like the north face. Thought I saw the Grindelwald area down below.
<<4. It follows from #2 above that DNDN likely knew on May 14, 2005 (and probably well before that) that the 9902a trial had badly failed on log-rank survival.>>
DNDN mgmt said in conf call in Feb 2005 that 9902A was unlikely to be stat sig for survival. They may not have known if it had actually failed or not at that time, because 9901's stat sig p value was driven in part by the # of 36-month survivors in the treatment arm and the # of placebos who died in the 30-36 month period. Thus it was entirely possible that when DNDN unblinded 9902A at the 30-month point in Jan 2005, they observed that the lifespans of the final enrollees could determine whether or not the final p value would be stat sig.
<<In the case of Provenge, DNDN did not start talking about Cox until well into 2005, when it was already clear to management that 9902a was coming up short.>>
Correct. Top-line survival results for the 9901 Phase III came back in October 2004, with the full log-rank survival data presented at the ASCO Prostate Symposium in Feb 2005. Since DNDN was considering filing the BLA on the two earlier Phase III trials (9901 and 9902A), they knew that the FDA biostatisticians would perform a Cox regression analysis on the trial data to see if the prognostic factors were biased in favor of the treatment arm. So, the lead investigator for 9901 performed the Cox regression analysis according to the widely used Halabi statistical nomogram in time to present at the main ASCO Conference in May 2005.
The exact methodology of the Cox analysis in the statistical analysis plan for 9901/9902A has not been widely publicized, but I'm assuming that the SAP specified it should be done according to the currently accepted practice...and since the Halabi nomogram has been the most widely used method for AIPC trials over the past several years and 9901's lead investigator was a collaborator on the original Halabi nomogram study, I would imagine that the Cox regression analysis for 9901 was on the up and up.
The fact that the 9902A Cox regression was done using the same five final prognostic factors that were stat sig for 9901, even though only two of them were stat sig individually, indicates to me that 9902A's Cox analysis was also on the up and up.
and you can't touch my vidow's peak either
This thread has become tiresome. Now is the time on Sprockets ven vee dance.
Actually, that's not the case. I'm only going by memory, and I'm either remembering a transcript or info from a secondhand source. I'm pretty sure it's there in a transcript someplace, though.
They said this back in late 2005, after ECCO. I believe it was Urdal, but don't quote me on that.
I should clarify, PGS, because I partially misread your post, that the first step that Higano did in the Cox analysis of 9902A she presented at ECCO 2005 was to take the exact same five stat sig final covariates from 9901's Cox regression and apply them to 9902A. There is no question about this. It is the unequivocal truth. The resulting p value was improved from 0.33 to 0.023. In addition to your references in the paragraph below, Higano also did what io_io said and what I said in my quotes in the last paragraph below.
-----------------------------------------------------------------------------------------------------------
PGS: ...The backwards and forwards / any which way reference by Gold was referring to the fact that if they took the 5 distilled covariates from 01 and applied them to the 01 dataset, then the p value was stat sig; or if they took the 5 distilled covariates from 01 and applied them to the combined 01+02A dataset, then it was stat sig again.>>
Walldiver: Correct, they ran the equations both of the ways you cite above.
PGS: Although DNDN may have started with the 20 prognostic factors and used the data from 02A to distill them, they did not present that data to the public (that I'm aware of). They only presented this outcome for 01, not 02A.>>
Walldiver: Correct, they did not present the 20 prog factor data to the public. However, I am taking DNDN mgmt at their word when they said that they also performed the Cox regression for 9902A by beginning with the same 20 prognostic factors as 9901, then running through the same steps in the exercise as they did in 9901, and then arriving finally with a stat sig p value. I think our differences over this issue are rooted in how much each of us believes in the veracity of DNDN mgmt.
<<...The backwards and forwards / any which way reference by Gold was referring to the fact that if they took the 5 distilled covariates from 01 and applied them to the 01 dataset, then the p value was stat sig; or if they took the 5 distilled covariates from 01 and applied them to the combined 01+02A dataset, then it was stat sig again.>>
Correct, they ran the equations both of the ways you cite above.
<<Although DNDN may have started with the 20 prognostic factors and used the data from 02A to distill them, they did not present that data to the public (that I'm aware of). They only presented this outcome for 01, not 02A.>>
Correct, they did not present the 20 prog factor data to the public. However, I am taking DNDN mgmt at their word when they said that they also performed the Cox regression for 9902A by beginning with the same 20 prognostic factors as 9901, then running through the same steps in the exercise as they did in 9901, and then arriving finally with a stat sig p value. I think our differences over this issue are rooted in how much each of us believes in the veracity of DNDN mgmt.
Looks like Sanofi is taking REGN's VEGF-Trap into five Phase III oncology trials, all in combination with chemo. You have to scroll down about halfway to get to the 2007 oncology program excerpt. I pasted the relevant section below the link.
http://biz.yahoo.com/prnews/070213/nytu067.html?.v=77
Oncology:
S-1 (agreement with Taiho) is a novel oral 5-FU derivative which delivers improvements on current fluoropyrimidine-based cancer therapies. In collaboration with Taiho, sanofi-aventis is conducting a registration seeking Phase III study, the FLAGS study, in first line advanced gastric cancer. Recruitment of the 1,050-patient targeted population is expected to complete in Q2 2007. Sanofi-aventis is also evaluating further development activities of S-1 in colorectal cancer, breast cancer and other 5-FU sensitive tumors.
Larotaxel (XRP9881) is a new taxane derivative. In a phase II study, larotaxel in monotherapy has proved to be active in metastatic breast cancer progressing after anthracycline/taxane, but did not reach superiority in a phase III study versus capecitabine in the same population. Following these results showing potential better efficacy and safety than Taxotere, a large phase III program in association with other cytotoxic agents is being implemented in breast and pancreas cancer.
XRP6258 is another new taxane derivative. It entered phase III development in the treatment of hormone refractory metastatic prostate cancer previously treated with a Taxotere containing regimen.
VEGF Trap (AVE0005) (agreement with Regeneron) is a new antiangiogenic agent to prevent neo-vascularization processes in tumors. Five Phase III studies in combination with chemotherapy in patients with several solid tumors are scheduled to start in 2007.
The first potential regulatory submission is planned in 2008.
GTOP and FVRL are trialing competing immunotherapy products, both in Phase III, for the same indication (NHL after Rituxan primary therapy), although FVRL's trial protocol might be different. I can't recall if there is more of a concurrent Rituxan component to the FVRL Phase III. Anyway, the setbacks you recall are related to the trials continuing after DSMB reviewed the interim data, with accompanying drops in the stock prices.
<<ingn. wht do sooooooo many short it.incredible bash from the street.com today as well.the stock to me has great potential. thoughts anyone>>
Here's one. TheStreet.com is correct.
Correct on both counts. BMY's CEO was heavily criticized for not doing the due diligence on Erbitux prior to signing the huge deal with IMCL a few months before the RTF.
The FDA has three options at the 45-60 day deadline for acceptance of the BLA:
Accept with Priority Review
Accept with Standard Review
RTF Notice (no acceptance)
OT-Yes, here at Alona Beach now. Seaquest Divers. Phils diving is pretty good, but Indonesia has the same type of diving, only more pristine.
Anyway, don't want to clutter up the board any more, so good luck and good dives!
OT-Thomas...Coron Bay wrecks...did you dive them and what did you think? I've been in Bohol and Boracay for the past week.
I sure hope your predictions come true Warren...but I would be overjoyed with a thumbs-up panel vote in March, Provenge approval in May, and a year-end price of $20.
Both the ODAC and the CTGTAC would have to be moved...it ain't gonna happen. Either 3/29 or 3/30 will be date.
re mitoxantrone trial in ADPC:
I cannot EVEN believe that this trial happened. A chemo drug + Lupron for ADPC? Downright irresponsible.
Well, I certainly believe DORB should be over a buck. What if the FDA says yes? What if it does $50mm sales in year 2?
io_io
I confess that I have owned Dor Biopharma for over a year in my Roth account. I've always considered it extremely speculative, so I rarely, if ever publicized my ownership. However, I wouldn't consider any attempt by CTIC to take over DORB as validation of DORB's product, or a harbinger of the FDA's decision. All it is, IMO, is a desperate attempt to acquire a product that has a decent chance of getting approved. CTIC has probably only seen the same data that DORB has released publically. I'd say that an accurate analogy for this attempted takeover would be:
CTIC, slowly sinking in quicksand, desperately reaching out to grasp a swinging vine that may or may not be in reach, and may or may not be sturdy enough to support CTIC's bloated, dying weight.
Wow, that's one of the worst insults I've ever seen on this board. Them's fightin' words!
That's probably a better summary of what I meant to say than my own summary was. Anyway, I believe that the positive effect on the stock price from the priority review decision will occur over the next couple months...perhaps all the way up to the day before the briefing docs are released.
<<-- First, why do you think the priority-vs-standard decision will be a positive/negative harbinger? I saw IV posts referencing statistical analyses of first round approval rates for priority and standard, but there was nothing really definitive in those posts. It seems to me the criteria for priority review do not necessarily predict anything about the criteria for approval, right? Or wrong?>>
Sorry, I didn't say whether or not the priority decision would be a positive or negative harbinger. I think you misquoted me. I said "incrementally positive or incrementally negative." Big difference. I think if the FDA had some issues, they would have granted standard review status to Provenge to give them more time, instead of an RTF.
<<-- Not sure how to interpret your "larger than incremental effect on the stock price" comment. Are you saying that whatever is announced(standard or priority) we may see an unjustifiably significant fall or rise? Given how impervious the stock has been to "good" news for the past year or so, my pessimistic side thinks standard may indeed result in a fall, but priority will likely only result in more sideways drifting.>>
Not sure where you come up with the phrase "unjustifiably significant fall or rise." That's not what "larger than incremental effect on the stock price" refers to. Now that priority has been granted, I can see the stock price gradually rising as more and more people realize that CBER appears to have a larger say in the approval question than CDER/ODAC. I also think there will be some short covering before the briefing doc release/advisory panel meeting occurs.
Yes, it happens sometimes. However, I do believe that the priority review or standard review decision will be an incrementally positive or incrementally negative harbinger of Provenge's chances at the FDA, and will have a larger than incremental effect on the stock price.
Nope. Not possible. Virtually every company over the past couple years that has submitted an NDA/BLA to the FDA has done so electronically.
Cash, no debt, increased buyback, oil dropping. Have to agree. eom
Yawn......EOM
Sorry, but that, again, is a lot of sound and fury signifying nothing. Yes, they will look for consistency across subgroups, but they're not going to care one whit about proof of the exact MOA, and I doubt they will place much emphasis on PK/PD. It's all about whether or not 9902A can be considered supportive, and if the survival dataset is sufficiently large.
<<How far in advance do we know who is going to be on the AC? 1 day or is it a surprise on the day of the event? Would be interesting to handicap based upon the committee members.>>
http://www.fda.gov/cber/advisory/ctgt/ctgtmembers.htm
I sure don't know how far in advance it will be. I think we can predict that Mule, Chappell, Kwak, Terry, and Urba from CTGTAC will be on it, with at least Hussain from ODAC if it is to be a hybrid committee. Gunter might have some participation as a non-voting member.
Based on his engineering prowess, I wonder why Tilden didn't immediately get hired by another wireless company...
That scenario could be possible. Another possible scenario for the briefing document is a favorable clinical review from the urologist/reviewer, but a questionable review from the biostatistician.
I do believe that the avg price of the stock will be higher from mid-January to late March than it is now if Provenge is granted priority review. IMO, there have to be some shorts who would at least partially cover their short position. I think the absence of an experienced CEO since Simonetti left in mid-2005 really hurt the stock price. Simonetti would have waited until January 2006 to do the secondary a year ago, instead of doing it in the teeth of tax-loss selling during the stock price's worst year on the market. The fact that the company could only get $4.50 per share at a time when the stock was in the low 6's absolutely put the kibosh on any sort of institutional support. In addition, there have been so many biotech blowups since early 2005 that most investors familiar with the DNDN story and looking to go long have probably decided to wait on the panel meeting or the briefing doc day before jumping in.
There will be more attempts to hold the price back even if the briefing documents are not negative for Provenge. I think there will be some more letup upon positive panel news. I would expect the stock to open in the teens when it resumes trading after a thumbs up from the panel. However, I think that there will always be a contingent of short-sellers around the stock until a couple of decent quarters of product sales.
I'm not sure if you were long during the period of late 2004 to early 2005. If you were, it was obvious that there was a concerted attempt by Brean Murray, UBS, and their hedge fund clients to keep the stock price down, especially around the time of the ASCO Prostate Symposium. This is a big factor in some of the more rabid DNDN longs taking their paranoia to absurd heights. Basically, after it was announced that 9901 had achieved stat sig overall survival in late Oct 2004, there was quite a big price spike from the 7s to the 13s. The short position doubled soon afterward. In 11/04, Brean Murray downgraded from a buy or strong buy with a price target in the 20s to a sell with a price target of $6...with no stop in between at a hold.
The analyst, Jonathan Aschoff, stated flat-out that DNDN mgmt was not telling the truth when it said the survival benefit was seen across all Gleason scores, and he further stated that the p value was entirely driven by an imbalance favoring the Provenge arm for Gleason scores less than or equal to 7, that the Provenge arm received more chemo during the 3-yr followup, and that the p value was likely just barely under 0.05. UBS jumped on the bandwagon in 1/05 after the announcement of the ttp endpoint miss in the 9902A trial, also citing the supposed Gleason score and post-Provenge chemo imbalances and a barely significant p value. DNDN mgmt had been saying all along that there were no imbalances in post-Provenge chemo, but Aschoff stated in his rpt that he did not believe mgmt.
Anyway, DNDN had been saying for months that they would not release full details about the 9901 trial survival results until the ASCO Prostate Symposium in 2/05. On 2/16, the day before the conference, the stock price climbed from the high 6s to the low 8s due to ABC-Chicago coming out with a story of this new prostate vaccine extending survival. When DNDN released the PR the next morning 2/17 detailing the 0.01 p value, the 34% vs 11% three-yr survival numbers, and the reiteration that a similar survival benefit for Provenge also occurred in pts with Gleason scores 8 and above, the price spiked very quickly in premarket to the mid-9's. Almost immediately, and still two days before DNDN was to present on 2/19 with full data details, UBS released a downgrade from hold to sell, again citing the supposed Gleason imbalance, and Brean again released a sell reiteration. The price dropped throughout the day, down into the high 7's. In addition, the price dropped almost exclusively on 100-share trades that machine-gunned the Bid down a penny at a time. Something like 18 million shares traded that day, approx 25 times the avg daily volume. There was definitely some deliberate capping going on. Anyway, neither analyst acknowledged in their rpt their mistaken assumptions that the p value would be barely under 0.05. It was clear that both brokerages had a ready-made report prepped for release, no matter what the data turned out to be, and these reports were clearly timed to help cap the price before options expiration the next day.
The presentation was on Saturday 2/19, and it was clear from the slides that the survival benefit was across all Gleason scores, so UBS and Brean were again wrong. However, they both released additional reports the following week reiterating their hatchet jobs from the previous Thursday, and neither acknowledged their previous accusations that DNDN mgmt was lying to investors about the Gleason score issue. Instead, they both cited 9901's missed primary endpoint of ttp (even though the p value was 0.061), and belittled DNDN's contention that survival was more important to the FDA than time to progression. However, their biggest argument now became the post-treatment chemo imbalance during followup, and there remained plenty of verbal accusations going around (this time not in writing), that BOTH DNDN mgmt and Dr. Small were promoting fraudulent data.
The funniest aspect of this story was the fact that the UBS analyst thought he found another imbalance favoring Provenge, this one being fewer patients with only soft tissue metastases (no bone mets) in the Provenge arm. Wow! Everyone knows that the major organs are classified under soft tissue for this purpose, so fewer visceral mets in the Provenge arm is huge! He was rather smug on the conference call the next week when he "ambushed" DNDN mgmt with this issue, even stating that soft tissue mets indicate a worse prognosis than bone mets. You could actually hear laughter in the background from Urdal and Gold when they explained to him that patients with visceral mets were denied enrollment in the trial, and that advanced prostate cancer pts with only soft tissue mets in the lymph actually have a BETTER prognosis than pts with bone mets. Needless to say, this particular "imbalance" didn't merit mention in that week's UBS rpt on DNDN.
A few months later, at the main ASCO conference, Dr. Small presented some slides showing that 37% of the Provenge arm got Taxotere after progression and 49% of the control arm did the same. A higher % of control arm pts also received any taxane in general, and the same for any other chemos. Again, no acknowledgement of this by UBS or Brean in their reports. Instead, they said that the Provenge pts received earlier chemo, and this drove the survival benefit.
Brean and UBS derive a hefty chunk of their revenue from their trading desks, with hedge funds being the primary contributors. There are articles on record citing certain powerful hedge fund managers demanding favorable treatment from the brokerage trading desks. I have no doubt that both of these brokerages will release reports criticizing the company upon news of the BLA's acceptance for review.
Priority review would indicate to me that if it is approved, the FDA understands that Provenge would be a significant improvement over the stand of care. I think that any price spike would be met by capping attempts by the short-sellers.
The immune assay to which you are referring is, I assume, the CD54 upregulation. This was prespecified in the trial design as a measurement of the patient's immune response/Provenge potency in the body. It turned out that the better the upregulation level, the longer the survival. Since DNDN can measure the CD54 upregulation in a patient's body immediately after reinfusion with the Provenge cassette, they can repeat the leukapheresis process for that particular visit if the upregulation level doesn't reach a certain threshold. This is an example of a metric that the FDA usually likes.
Yes, in DNDN's case, always have at least two backups for that software counting program that counts survivors in a drug trial:
Backup #1: an abacus
Backup #2: a calculator
OT-"I'll take 50 sliders, 5 fries, and 5 cherry cokes...." "Make mine the same except I'll have diet coke..."
I'm going to guess either "Harold and Kumar Go To White Castle"....or "Supersize Me."
In fact, it's probably the latter
Shire and/or New River will get swallowed up by big pharma, as will Sepracor, Neurocrine, Regeneron, and Repros, with Medarex taken over by either BP or Big Bio.