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CORT shouldn't be considered a turnaround candidate. It's already tripled from a year ago.
There is no time limit on this trial. Every patient is followed until death, or until the 360th death.
Re trp-p8: I think the last bit of real good news on it was about five years ago. So, if you add up the days in five years, you get:
366 + (365 x 4) = 1826 days
Then, add 1/1826 for each day starting tomorrow, so the chance in the next month of any good news on trp-p8, by my calculations, would be 30/1826 or 1.6%.
<<Just to make sure that we are not talking past each other - in the post to which your post is a response I estimated the powering after CR (and assuming all the alpha is in the final) of a little less than 90% assuming an HR of 1.40.>>
I was aware of that, but I believe that the bone met factor was the single most important factor in the nomogram. We could see a similar % of surviving Provenge patients beyond 36 months to the previous two trials, which would be combined with a lower % of deaths in the Provenge arm than in the previous two trials due to the cutoff point of 360 deaths.
<<PS A limiting factor on the theory that those who live beyond 36 months will hugely drive the p value: the remaining patients of the placebo arm are such a small percentage of the total that even if as a group their HR is 3.0 they can't hugely effect the p value>>
On second thought after looking at these numbers, if the trial continues past the assumed interim look in November 2008, and Provenge is showing a clinical benefit but not yet stat sig, it will be more likely for the final look/360th death to occur at least a full year later. Not sure what I was thinking.
So, assuming the final look happens in November 2009, approximately 325 patients will have been enrolled for 45 to 77 months. Due to the more equitable stratification for bone mets than the previous two trials, we could see 40-50% of the ~217 patients in the Provenge arm of this cohort survive at least 36 months. That's 87 to 108 patients. We could also see 20-25% (43-54) of these 217 Provenge pts still alive at the 360th death/final unblinding, compared to only 2-10% (2-11) in the control arm. This assumes that Provenge works, of course.
For the next oldest cohort of approx 75 patients enrolled for 33 to 44 months, it's entirely possible that 20 pts out of the 50 in the Provenge arm are still alive if the 360th death occurs in 11/09.
For the 70 pts in the Provenge arm out of the approx 105 pts enrolled for 25 to 32 months, it's entirely possible that 35 to 45 are still alive. I do acknowledge that the median survival for the 35 pts in the control arm enrolled for 25 to 32 months might not be met by the time of the final unblinding. The other assumption I'm making here is 50% docetaxel usage in the Provenge arm and 67% in the control arm.
Yes, but I think the Cox regression p value will be better than the log rank p value, even with the equalizing effect of a much larger trial. Both arms should be stratified for Gleason score, Zometa use, and # of bone mets, but not LDH and PSA. I think the latter two factors, along with bone mets, will figure into the Cox exercise. If the trial is well balanced, I think it's plausible that the Cox regression p value could be half that of the log rank p value. From what we know of Provenge, if the final look happens in June 2009, approximately 325 patients will have been enrolled for 40 to 72 months, approx 75 patients for 28 to 39 months, and approx 105 patients for 20 to 27 months. I think that will be long enough, if Provenge does indeed have a clinical benefit, to hit stat sig on the Cox regression primary analysis, even if only 0.025 of the p value is reserved for the final look.
Yes, if Provenge works, the potential longer survival time of the early enrollees should have some sort of an offsetting effect. There were 179 patients enrolled as of 2/6/06. Nothing has been released about the enrollment rate before that date, although Nicole Provost presented data from 99 patients at the CTGTAC in February or March of 2006. I would estimate that there were about that many enrolled as of Feb 2005, meaning that approx 20% of the patients in the trial will have been enrolled for 45 to 65 months if the interim look happens in Nov 2008.
The company hinted earlier this year that they might request the p value figure from the DSMB, and if it's below 0.05 but misses the interim alpha, then refile the BLA based on 9902B being a second statistically significant randomized trial in overall survival. To me, that's the only logical reason for the supposed interim alpha to be in the 0.01 range. Otherwise, why not make it higher, like 0.02 or 0.025? If Provenge has a clinical benefit, then it should easily beat 0.025 or 0.03 at the final look with a large trial of over 500 patients and 360 death events. They can't keep so many personnel around doing nothing, they don't have an infinite supply of cash, and there are other competing treatments coming down the pike, like a new AZN drug and possibly Avastin and GVAX.
If this is the usual situation and the DSMB definitely won't give them any additional info beyond the continue, stop for efficacy, or stop for futility scenarios, then might as well designate the interim p value to be somewhere between 0.005 and 0.01.
I don't know if that would be allowable, and I haven't heard of it being done before. Not to say it hasn't been done before, of course.
9901 was a much smaller trial--only 127 patients. Your chances of hitting stat sig at the interim are much higher for 9902B, which has slightly more than 500 patients. However, if the interim look happens on 11/6/08 (probably around the 180th death), then only approx 60% of the patients in the trial will have been enrolled for over 24 months, and 75% enrolled for at least 20 months. The more recent enrollees tend to muck up the data, since the ones still alive at that point get tallied up for however many months they've been enrolled. So, it's tougher for the Provenge survival curve to gain separation from the control curve, as there usually is a bigger difference in the two curves from the 30-month point and on.
<<Just wondering if anyone subscribes to David Miller's BSR investment letter. Is it worth trying out? What do people think of David Miller. I listen to the DNDN conference calls and he always seems to ask the most intelligent and knowledgeable questions. I know he is a DNDN homer but he does seem to know DNDN inside and out.>>
A lot of us subscribe, and it's well worth it IMO for biotech education. Miller knows DNDN better than any of the brokerage analysts and financial reporters.
<<What are the chances that DNDN will still file at the interim if results show a trend toward improving survival but just misses statistical significance?>>
It depends on what the DSMB tells them. Most of us are assuming that the p value reserved for the interim alpha is very close to 0.01. If it's above 0.05, there's probably no way that they file. If it's between 0.01 and 0.05, I think it's a coin flip that they file.
<<Also would 9901 been statistically significant for survival at an interim analysis?>>
It was not, as it was unblinded a couple of times for interim peeks. The last interim unblinding was at the 30-month point, and it was barely stat sig for the Gleason 7 or less subgroup, but not stat sig overall.
In 1/04, DNDN released news that interim survival data was stat sig for the Gleason 7 or less subgroup in the 9901 trial. Then in 10/04, the final survival data came in and it was stat sig for the entire intent to treat group (p=0.01). There is a lot of info in the ReadMeFirst page for DNDN.
Turnaround stocks: ACHN, ADLR, AEZS, CGPI, CEGE, CVTX, ENCY, FVRL, IDIX, INSM, JAV, NABI, OPXA, PANC, PCYC, SCLN, and YMI.
I included revenue generators CGPI, CVTX, ENCY, and IDIX since you included VPHM, so I assume they're eligible. I didn't include DSCO because it's not down appreciably from January, but I think it could be considered a turnaround candidate because it's been down for a lot longer than one year, and has a shot at taking off if the FDA finally approves Surfaxin in Q1 2008. If you agree, then we can add DSCO to the above list.
Good find there, Biowatch. Thanks. eom
Jim, the link to that blog was posted yesterday by Catchnrel and commented on by me. Sramana Mitra is highly respected in the wireless and electronic gadget industries, in fact she's up there with Tero, or even above him in esteem. Any guest host who gets a chance to post frequently on her blog will know what they're talking about.
Catchnrel, here is Vijay's bio. Great find BTW. Sramana Mitra is up there with Tero in terms of credibility, so a guest author on her blog is going to be perceived as being important.
http://sramanamitra.com/guests/#nagarajanv
Vijay Nagarajan
As an engineer at Atheros, Vijay works to bring state-of-the-art wireless systems to the consumer. Previously, he was with Denver-based TensorComm, a start-up providing advanced receiver solutions for CDMA/WCDMA networks. Vijay has over 15 published patent applications and multiple technical papers/articles in mobile receiver design. His active engineering experience, along with his penchant for market research/analysis, helps provide unique perspectives and insider insights about wireless industry trends which he jots down in his analyst blog. Vijay holds an M.S(EE) degree from the University of Colorado, Boulder and a B.S degree from the College of Engineering, Guindy, India. Vijay writes regularly at his blog, Wireless Industry Analyst.
* QualComm: The Margins
* QualComm: The Aftermath
* QualComm: Legal Battles Galore
* QualComm: The 3G Goldmine
* QualComm: Digging Gold
DNDN-I think these questions are best left to the company. I do know that in late 2005, over two years after the start of the trial, the SPA was amended so that patients with mild pain could be admitted. This was due to slow enrollment. So for these patients, it's tough to know how pain measurement would contribute to progression and subsequent crossover.
I haven't yet seen any statistics on GVAX plus/minus Taxotere in randomized trials. Even with Provenge, the later Taxotere patients are merely a self-selected subgroup. So right now, it's only an interesting theory, albeit with much potential.
DNDN -- Doc, docetaxel had already been approved for breast cancer, so a lot of patients in both arms were able to take it off label. In the 9901 trial, 37% of the pts in the Provenge arm got docetaxel, while 49% of the control arm took it. Supposedly, the patients in the Provenge arm averaged fewer cycles of docetaxel than those in the control arm.
OT-The Euros must think this administration is full of standup comics. I wonder how many of them had to pull themselves off the floor after reading that quote.
Just imagine if Provenge doesn't hit stat sig on the interim look. We'll have to put up with this guy's crap for another three years. Even if it hits stat sig on the final look, he will play up other treatments and minimize the market potential. Once Provenge begins to dominate the marketplace, then he will go on and on about patent expiration and biogenerics.
Yes to the first question and not sure to the second. By late 2008, 50-60% of the patients will have been enrolled for two years or more, and about 30% for three years or more. The important additional stratification factor for 9902B's randomization is the number of bone mets, which was perhaps the greatest predictive factor for a given patient's survival in both 9901 and 9902A. It worked against the Provenge arm in both 9901 and 9902A, but in the latter trial to a greater extent. So that should help, along with the fact that Cox will be the primary analysis. It's still very far from a slam dunk on the interim.
If this is true for certain, it obviously lowers the odds of Provenge being approved on the interim survival data. I was thinking prior to today that Provenge in 9902B had about a 2/3 chance of an interim p value being 0.05 or better, and about a 1/3 chance of being 0.01 or better. I'm assuming that 0.01 is the interim alpha and 180 deaths is the cutoff point. If this is all they're going to get from the DSMB, then it's asinine IMO to only allocate 0.01 for the interim alpha. They should allocate 0.02 for the interim and 0.03 for the final, if all they're going to get from the DSMB is whether or not the interim has been met. By 2011, there could be another therapeutic agent on the market. What if they find out in 2010 that the interim was 0.015 and the final was something great like <0.0001? That's two years of lost revenue in a marketplace with only Taxotere as the relevant competition.............dumb.
OT-I wonder if Rudy agrees with Pat that 9/11 happened because God punished America for being secular.
OT-Thanks Steve. Just to let you know, the Giant Moron Magnet (aka the Creation Museum) is expanding its operations. They're taking donations, and hope to raise $500,000. I guess those dinosaur figures wearing saddles are expensive. As Lewis Black and Bill Maher have said, "Didn't we laugh at this when we were kids in the 1960s, watching The Flintstones? Now they want to teach this bull***t in schools!"
http://www.kentucky.com/news/state/story/228302.html
Sam, SPAs are privileged communications. We don't know what's in the 9902B SPA.
Nope...they are currently in preliminary negotiations with the EU, most likely about whether or not the EU would accept a statistically significant survival result in the ongoing 9902B trial for approval. If not, the company and its future partner would have to conduct another trial.
<<I see that the manipulators have managed to knock out the IV board today, no telling what they have up their sleeves while we are blinded, and not able to read Mings sage postings.>>
LOL, you're implicitly admitting that you read too many of casey's and crou's posts.
OT-It's a stockpicker's market, with rapid growth fueling the limited number of standouts. You have GOOG, RIMM, BIDU, and AAPL the leaders in high tech, FSLR and SPWR the leaders in solar energy, ONXX the biotech leader, and ISRG the leader in high tech medical devices, and then you have the natural resource stocks. Some favorable court decisions and IDCC could join the high tech leaders.
ONXX - I've been holding my entire ONXX position, because (a) I see it as a long-term successful cancer play, especially in increasingly prosperous Asia where liver cancer is so prevalent, (b) the potential, albeit unlikely, for a Bayer buyout--they should have bought it out in the 30's, and (c) it's a hot stockpicker's market and they love growth, and ONXX is to biotech what RIMM, GOOG, and AAPL are to high tech and ISRG is to medical devices.
OT-Yes, I spoke unscientifically with the term "cure," should have said what you said. The condition can also be reversed to a certain extent, before it gets too severe.
OT-Right, who needs it, but that illustrates my point. He probably picked it up via repeated exposures (bites) over a 3-yr period, and it's easily treatable with cheap drugs. Bancroftian filiariasis, schistosomiasis (bilharzia), and onchocerciasis (river blindness), are all diseases primarily of extreme poverty. The first two develop via repeated exposures to Culex mosquitos and blackflies, respectively, while schisto is contracted via one exposure (but is also easily treated by cheap medication). The problem is, especially in sub-Saharan Africa, 50 cents a pill to cure the disease is not so cheap.
OT-filiariasis from the Culex mosquito usually happens due to repeated bites and multiple exposures. Dengue can happen from just one exposure. I had forgotten that Thomas was in the Phils...in urban areas there, you usually don't need to worry about malaria. However, dengue thrives in urban areas, especially during the rainy season. As dengue has been recently spreading to the SE USA and Texas, a dengue vaccine could be lucrative for its developer.
OT-Thomas, you must reside in Texas or the Southeast. Best of luck with your case, and yes, I know that dengue has made a foothold recently in the USA.
I did see the piece on the Celebes Sea expedition. I've dived that area a few times. You'll see more species of coral (sometimes 20+) on one dive in that region than exist in the entire Caribbean. Bunaken Island off North Sulawesi and all of Sipadan off Borneo have perfect wall dives...you start by going down to 100' depth, swim along the wall, with the wall side having reef fish and the open ocean side having pelagics. Then you swim back in the other direction at 60', and spend the last 20 minutes of your dive off-gassing above the wall and over the reef.
At the end of my last dive at 15' depth at Bunaken's Lekuan II, I saw a highly venomous banded sea krait (fortunately it's not aggressive), and five or six species of damselfish that were living inside the same number of species of sea anemone. Along the wall, we saw two spotted eagle rays, huge schools of Moorish Idols (you never see these in schools), and a manta ray. We had well over 200 feet of visibility...it seemed like you could see all the way to the bottom, but of course one can't, it's too deep. This was back in early 1999, when you could stay in a guest house on Bunaken for $5 a day, including three meals.
Agree wholeheartedly with both this post and your next about two of our long-term longs. Last week I increased a decent position in IDCC that I had reinitiated in the low 20's, and I'll be looking to add some more this quarter depending on how some of my other positions do.
Yes, and I wonder/suspect if it was his advice that led NOVC to change ONLY the control arm to the once per three week Taxotere regimen. An absolutely stunning (and obvious at the time) miscalculation.
I'll be one of the first recipients of any approved dengue vaccine. I travel a lot to the tropics and the two biggest risks for me are dengue and road accidents...but if you already have dengue, then getting it again is a HUGE risk, as DHF is extremely dangerous and affects those who get infected for the second time.
I would have to agree, especially when one checks out NOVC's chart from the day it signed the SGP partnership to the end of last week. It had already dropped 10 bucks (~60%) before yesterday's sledgehammer.
Your post implied that you wanted DNDN to have a special unblinding for TTP. That's what's crazy. The TTP metric, if stat sig, could provide additional supportive evidence if the interim survival p value is between 0.01 and 0.05...but it would be crazy to do a special unblinding for TTP instead of waiting six more months for the ~180th death and looking at TTP at that time.
I don't know...I imagine a lot of negotiation with the FDA would have gone on when they amended the SPA...but they did amend the SPA in order to de-emphasize TTP.
Dooooood, that's some crazy sh*t...apply for approval on 9901/9902A survival while minimizing the importance of TTP, then go outside the SPA for 9902B AND go outside the original premise for the 9901/9902A filing by going for approval on 9902B TTP, which has suddenly become important again.