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I would imagine we saw massive short covering in the early hours, then more shorting as it went up into the low teens, and more shorting on the way down. If the company does not price their secondary ASAP, then they don't deserve to hit stat sig on the interim look. Raising ~$50mm now means that you won't be hammered down immediately before the interim data release. Raising >150mm now means you can restart the pipeline.
re ONXX and BAY: we have already known for several months that the Nexavar liver cancer results were stat sig. I think that qualifies as compelling, so nothing new in this quote.
That has to be what happened today. Massive short covering. The shorts must have been expecting that the FDA would either require stat sig on the 9902B IMPACT final look, or stat sig in a fourth trial...absolutely amazing, and I hope some of the long-time longs were able to lighten up on that spike into the low teens. Did it really go up to $13 this morning? I just woke up 20 minutes ago. One more thing, if Mitch and Greg are smart, they price that offering and sell those shares right away.
re CYPB: iwfal's argument is that the drug gets approved for the pain indication on the two previous Phase 3 trials, not the fibro indication. To expand into the fibro indication, there is the ongoing Phase 3.
Novacea and Schering-Plough Enter Into Worldwide Development and Commercialization Agreement for Asentar, a Novel Treatment for Prostate Cancer
Wednesday May 30, 9:55 am ET
http://biz.yahoo.com/iw/070530/0259129.html
SOUTH SAN FRANCISCO, CA and KENILWORTH, NJ--(MARKET WIRE)--May 30, 2007 -- Novacea, Inc. (NasdaqGM:NOVC - News) and Schering-Plough Corporation (NYSE:SGP - News) today announced that they have entered into an exclusive worldwide license agreement for the development and commercialization of Asentar(TM) (DN-101). Novacea is currently conducting a large international Phase 3 trial (ASCENT-2) evaluating Asentar in 900 patients with androgen-independent prostate cancer (AIPC). Asentar is a novel, proprietary, high-dose oral formulation of calcitriol, a potent hormone that exerts its effects through the vitamin D receptor (VDR).
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Under the terms of the agreement, Novacea will receive an upfront payment of $60 million, including $35 million as reimbursement for past research and development expenses, a license fee of $25 million, as well as a commitment by Schering-Plough to purchase $12 million of Novacea common stock at a predetermined price within ten days of the closing. Additionally, the agreement provides Novacea with potential pre-commercial milestone payments of up to $380 million, and tiered royalties on worldwide sales of Asentar. Closing of the transaction is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act (HSR) and is anticipated to occur following HSR clearance.
Schering-Plough will be responsible for all forward development costs in exploring indications for earlier stages of prostate cancer, such as androgen-dependent prostate cancer (ADPC) and adjuvant therapy and will lead all global commercialization efforts for Asentar. Novacea will provide medical support to Schering-Plough's commercial operations for Asentar in the United States, including deployment of their Medical Science Liaisons, which will be funded by Schering-Plough.
"A corporate partnership has been a significant corporate goal for 2007, and we are proud to be co-developing Asentar with a highly-respected pharmaceutical company such as Schering-Plough. The partnership leverages Novacea's existing capabilities with Schering-Plough's experienced development, regulatory and commercial teams and will provide Novacea with an opportunity to support the commercialization of Asentar in the United States. Additionally, this agreement provides us with substantial funding for the continued development of our operations," said John P. Walker, Novacea's chairman and interim chief executive officer.
"This agreement with Novacea allows us the potential opportunity to extend our oncology pipeline into a tumor with significant unmet need," said Thomas P. Koestler, Ph.D. executive vice president and president of Schering-Plough Research Institute. "Asentar represents an innovative research development and reinforces our continual commitment to patients."
About Asentar
Asentar is currently being developed as an oral treatment in combination with Taxotere® (docetaxel) for the treatment of AIPC. Prostate cancer is the second leading cause of cancer death in men with approximately 232,000 new cases and 30,000 deaths in the U.S. in 2005. AIPC is an advanced disease state of prostate cancer. Based on results of Novacea's completed Phase 2 clinical trial, known as ASCENT, the use of weekly Asentar in combination with weekly Taxotere may provide AIPC patients with an innovative cancer therapy that may prolong survival with the potential in reducing some of the toxicities and complications normally associated with chemotherapy. Novacea is now evaluating the benefits of Asentar in a 900-patient Phase 3 trial, known as ASCENT-2, which uses overall survival as the primary endpoint and compares weekly Asentar plus Taxotere to the current standard of care in the treatment of AIPC.
The exact wording of the question after it was changed was, "Is there substantial evidence of efficacy?"
OT-My apologies to the board for my one off-topic post here in the past two months. Badgerkid, I know you were horribly inconvenienced by it...I hope you can recover enough to have a good weekend.
OT-Slight correction...the Provenge vote was 17-0 for safety and 13-4 for efficacy. However, the two most vocal opponents of Provenge on the panel were the same two who wrote letters to the FDA afterward urging the agency not to approve, and were the only two voters who had to file conflict of interest waivers because of grant money accepted from Provenge's potential competitors.
Bob...just wondering...do you do a lot of texting?
There is a very well-known example that has been discussed on this board in the past, for a drug that would compete with Tracleer.
Without looking at those posts, I would find it hard to believe that approval on a stat sig 9902B interim look is not written into the SPA. Not sure where Duncan is coming from. Why would 9902B be different from every other pivotal trial that has survival as the primary endpoint?
I think the company miscalculated, or the agency misled them, regarding the close TTP miss. I do agree that the company should have fought for the 0.052 p value at the panel meeting. However, the basis of the BLA was survival, and the company wanted to focus on that endpoint. I, along with several others, believed that the company's presentation at the panel meeting could have been a lot better. OTOH, I think in the end it wouldn't have made any difference if they had been able to persuade the committee members that the TTP p value should have been 0.052. Scher, Fleming, Hussain, and Pazdur still would have been opposed to approval.
I think Fleming would have still insisted that the 9901 TTP was a miss. Pazdur, Hussain, and Scher would have directed their argument more toward 9902A and the relatively small number of patients in the two trials...Scher's motivation being different than the others, because he is on NOVC's scientific advisory board as lead investigator of the Asentar Phase III in HRPC. It's still amazing to me that he was able to get the conflict of interest waiver.
They can't use longer-term data than the specified three years for 9901/9902A because it wasn't in the protocol.
Correct me if I'm wrong, but I thought that you yourself mentioned that similar log rank results to the combined 9901/9902A dataset would have something like a 50-50 shot of hitting stat sig on the interim look if the reserved alpha was 0.01. I think that's assuming an HR of about 1.45, right? Assuming that the final unblinding occurs after Q1 2010, and considering (1) the larger trial size and (2) this would take place over three years after the 400th patient enrolled, then if Provenge is effective, it should easily beat p=0.03. So if that is the case then why not reserve more than what you normally would at the first interim?
Steve, it's possible that they could set the alpha as high as 0.02 for the interim look. That's what I would do.
I do tend to disagree slightly with his opinion on satra...progression of pain was encompassed within the SPA's time to progression endpoint, so there is some, albeit limited, clinical significance. However, I completely agree with him that the convening of ODAC is Pazdur's dog and pony show to let PCa patients know that he is really a good guy. This NDA never would have had to go up before ODAC if he wasn't getting heat over the Provenge decision. The Phase III was right up Pazdur's alley: 950 patients, high degree of stat sig on a surrogate endpoint. In addition, the drug is right up Pazdur's alley as well: it's a platinum chemo drug with all sorts of nasty side effects, but not as nasty as Taxotere or even possibly other platinum chemos.
Yes, but at least that bone mets factor won't be working against Provenge.
Let's say the 180th event takes place in July 2008, and enrollment is completed in Sept 2007. There will be a lot of survivors in both arms who enrolled 10-15 months prior to 7/08. These patients still need to be counted in the overall intent to treat survival analysis...so there won't be much of a difference in the survival curves for these recent enrollees...thus hurting the overall p value.
Yep...although we haven't been able to figure out what exactly has been changed from the old guidelines. If the new guidelines are more lenient, then I think there could be some significance in the fact that the FDA said no to approval six days before the guideline change. Also, it's possible that the FDA just got around to posting these guidelines, and they've already been in effect for some time.
Well, we do know for a fact that 179 patients were enrolled as of 2/6/06, and 294 as of 11/6/06. I'm guessing that the numbers from Dr. Provost's Feb 2006 meeting before CTGTAC in which she discussed the CD54 data for 99 patients, if those 99 did indeed represent an accurate full enrollment figure, were from early Feb 2005. If the 180th event does in fact take place in 2H 2008, perhaps 30% of the patients will have been followed for at least three years.
I'm pretty sure that Clark was comparing the trial size of 9902A to the trial size of 9901 in his analysis, not the small trial size of 9902A per se.
I would be very confident of the final look coming back stat sig.
Let's assume that the 180th event occurs on July 1, 2008 and the DSMB unblinds for the first interim look. Let's also assume that 120 patients had enrolled by July 1, 2005, approximately two years after the first patient enrolled. Let's further assume that enrollment for the first year was linear, at 4 patients per month. The second year enrollment assumption is 6 patients per month. I wonder how much the extra time beyond three years the long-term survivors are followed would help the p value.
Looking at some of the simulations, I'm starting to wonder if it would be better for the company if the interim unblinding occurs in the 210-240 event range instead, and reserved alpha is 0.02...
9902B Q & A:
Q: What factors led to the relatively poor results of 9902A?
A: Main reason was strong # of bone metastases factor favoring the placebo arm...secondary reason was smaller trial size.
Q: Why should the results of 9902B look much more like 9901 than 9902A at the interim and final?
A: One of the stratification factors in 9902B will be # of bone metastases...this and the much larger size of the trial should help balance out the likelihood of a higher % of placebo crossovers.
Q: Could the results of a few patients sway the results one way or the other if we roughly mirrored the combined 9901 and 9902A results?
A: This would be more possible at the interim look, which probably will occur around the 180-death point...and yes, there is a possibility of this happening if the results of the Provenge arm are moderately successful.
Q: How might the relatively sicker patient population affect the results?
A: It's hard to say...I think a bigger factor could be how balanced the followup Taxotere usage is.
Q: How might slow ramp up on enrollment of 9902B affect the results at the interim and final for an event given trial?
A: There will be a greater effect at the interim look. There will be a lot more censored patients who are more recent enrollees, and this will be a confounding factor.
Q: How do long-term survivors factor into the results of an event driven trial?
A: This is one of the most promising factors for the Provenge arm. In 9901/9902A, the 36-month survivors had to be censored at the 36-month point. In other words, the Provenge arm got no p-value bonus beyond 36 months for Mr. Garcia, who is a 7-year survivor. In 9901, we know that 28/82 survived 36 months, and that eight more deaths were reported in the BLA for those 36-month survivors. Does that mean that 20/82 were alive at the time of the panel meeting? Possibly, but it may just mean that we lost contact with the other 19 besides Mr. Garcia.
Agreed...unless a partnership is close, no time is better than now to raise money.
Thanks, but no thanks. This tactic by INVESTORS is probably not going to do any good, and smacks of financial self-interest. We made our play already, prior to the decision, and even provided the PCa advocacy groups with some factual background on Provenge, and on Scher and Hussain's prior statements that contradicted their actions regarding Provenge. I personally called a number of Congressional offices and PCa advocates in April. The other side has bigger guns (especially Pazdur and Fleming), and the philosophy of the FDA is not going to change. There is currently widespread support on Capitol Hill for reining in Big Pharma and Big Bio due to drug safety issues. Even though this has nothing to do with Provenge, Capitol Hill will lumped it in together with the drug safety issue and the renewal of the PDUFA. As much as I hate to say it, FDA reversal is not going to happen without stat sig survival data from 9902B. Hopefully this happens at the interim look next year.
Until P-11 comes back with great results, it's out as a potential factor in getting the FDA to change its mind.
I thought the company had said, prior to the cc, that they would meet with the FDA in June...but then on the cc they didn't specify. I can't see it taking any longer than that to meet with the agency.
Survival isn't as important as the time to distant metastases endpoint. However, the PSA velocity endpoint needs to be followed longer for it to become stat sig. Hopefully, there will be a few more patients in the Provenge arm taking a little longer to hit the 3.0 level to bring the primary endpoint under 0.05. So far, these results aren't stellar.
Just an amendment to the BLA...probably take anywhere from two to four months after the trial results for the company to compile everything. Then the FDA would have six months to respond.
I'm not sure that there is much to the conversations, if any, going on between DNDN and FDA. I think the substantial conversation will be in June at the meeting about which DNDN has informed us.
Additional clinical data means additional clinical data. That means 9902B, and almost surely means survival data from 9902B. Interim survival data probably won't be available until 2008, and likely 2H 2008.
DNDN Read Me First
Edit: transcript of 5/10 complete response letter conference call, courtesy of froggmister:
http://www1.investorvillage.com/smbd.asp?mb=971&pt=msg&mid=2141290
Edits: Froggmister's April research link on I-Village
http://tinyurl.com/yqw9oo
recap of pivotal moments of panel meeting as relayed by posts on I-Village board...requested by rkcrules
http://tinyurl.com/3a89k2
http://tinyurl.com/2nfe5p
finally, scroll down to corrected link to K-M survival curves for 9901 and 9902A
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Full presentation with slides of Dr. Petrylak's presentation of Provenge plus Taxotere patients, directions to presentation courtesy of stuck_holder
http://www.investorshub.com/boards/read_msg.asp?message_id=18179649
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From I-Village, a good summary of DNDN/Provenge story to date, with an opinion at the end
http://tinyurl.com/2kv2t4
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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-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/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
I think we could get final data on the primary endpoint of PSA velocity anytime after EOY 2007. Final data for the time to distant metastases endpoint could be available in 2009 at the very earliest.
I think that can be interpreted either way.
I think the guidelines published today are quite similar to the old guidelines, although before I hadn't noticed the language about trial success in a different stage of the same disease.
Witchhollow, see the edit to my previous post.
I noticed on Page 4 or 5 of the new guidelines that data from a trial for a different stage of the targeted disease can be used to support approval...hmmm...I know it's a long shot, but it would be interesting to see if they unblind PROTECT again in Q4, and look specifically at the time to distant metastases endpoint.
Edit: of course, this assumes that the agency isn't just paying lip service to its own new guidelines.
re Acorda: any chance of finding out who the brokerage and analyst are who released that report?
The Taxotere pivotal Phase III that got its approval had a median survival of 18.9 months in the intent to treat, once per three weeks, Taxotere arm and 16.5 months in the control arm. The once per week Taxotere arm had ~17.0 months MS and was not stat sig. There were ~300 patients in each of the three arms.
However, the TAX327 trial enrollment was split 50-50 between asymptomatic patients and symptomatic patients (bone pain). At the ASCO Prostate Symposium in Feb 07, Sanofi released the subgroup results for the stat sig arm. There were ~150 asymptomatic pts in this arm vs ~150 asymptomatics in the control arm. The MS breakdown for these pts was 23.0 months Tax vs 19.8 months control.
Any CEGE investor not aware of this fact has invested in the stock without knowing the single most important piece of information in CEGE's history as a company.