Expect Lawsuits

The anti Provenge JNCI article written by an ex hedge fund employee was debunked by Ocyan and other knowledgeable people in yesterdays issue of Pharmalot.

Here is Ocyan's take on the so called Immunodepletion theory that is being promoted by one of the hedge funds who are short Dendreon.

"The Immunodepletion theory in Huber’s paper has no merit. The survival analysis for the subgroup division at 65 was likely biased and spurious. Randomization even failed to balance the numbers of patients on the two trial arms of this partition so there was little hope that other crucial diagnostic factors would be balanced. Using this statistically spurious result to launch a hypothesis that Provenge did not work was naive from mathematical point of view.

Nonetheless, that naivete quickly became a pernicious scientific deception when Huber et al proposed an elaborate immunological theory to explain the abnormal results without vetting the truth of some of its obvious predictions.

For example, if about 90% of the immune cells of a patient on the control arm of the trials were indeed depleted by the leukapheresis procedure as Huber et al asserted, those patients should have become rather sick quickly compared to patients on the treatment arm. Yet, the safety database showed no such imbalance. Indeed, the fact is that most immune cells are sequestered in various tissues so that less than 2% of them would be taken in a leukapheresis procedure. The human body produces more than this cell count daily.

Next, consider the conclusion that Provenge was just a placebo treatment so that the survival benefits seen in the trials were merely from harm done to patients on the control arm. First, if that was the case, patients on the control arm should have died en masse early. Yet the survival curves showed that the two populations performed about the same for several months before separating in Provenge’s favor. Then, a recent analysis of the data showed that patients on the control arm who received a weak form of Provenge made from salvaged blood (ie, the colloquial Frovenge) after disease progression (often months after randomization) lived far longer than those who did not get it. If Provenge was a placebo, Frovenge must be even worse. Why did these Frovenge patients on the control arm of the trials perform so well when receiving it only after months of lacking treatment?

When a scientist proposes a theory, it is incumbent upon her/him to at least vet simple predictions to see if they hold up. Huber et al did none of that. Instead, they published a theory indicting Provenge, then ask others to prove them wrong. This is arrogant and pernicious! These authors should be ashamed of themselves.

Huber et al should also think about the harm that they might have done to doctors and patients without the statistical and immunological background to understand the shortcomings of their Immunodepletion theory. If those patients and doctors end up avoiding a treatment that may extend their life, such harm will be attributed directly to their work.

Lastly, I’d like to quickly address this statement: “There has also been debate about effectiveness because Provenge does not shrink tumors.” This is an oft-repeated misconception about statistics. The Provenge trials did not demonstrate statistical significance results on Time to Progression. That is not the same as “Provenge does not shrink tumors”. Unlike a chemotherapy that delivers a toxin to tumors (and other parts of the body too), an immunotherapy often takes months to ramp up the immune system. During that time, some tumors may get larger and some new ones may develop. Too frequent radiographical assessments might catch these cases and showed that disease has progressed while, in fact, the immune system was just getting started to exert its protection. So, the lack of a statistical significant result on Time to Progression is far more likely due to the measurement methodology than because of the efficacy of Provenge. Indeed, with three separate phase-3 trials showing survival benefits, it should be clear that Provenge did arrest the disease at some point.

There is a need to develop new measuring methods to see how Provenge and, indeed, other immunotherapies help stopping or slowing down cancers. That’s what the various Cancer Vaccine Workshops organized by the FDA tried to do. See the references in the Wikipedia page on Provenge (Sipuleucel-t) for details."

 

Gold et al should think about the harm they have done to employees, shareholders and cancer patients before they go to sleep every night. He is a greedy psychopath who put his own greedy interests above all else. Hopefully his next few years will be spent in prison.

 

Boo-Yah. Thats how you do it. You need a medical and preferably an immunology background to make the assertions Huber et al has made. This was brilliantly written by someone who clearly has MEDICAL training. Is is not totally transparent that Huber et el have a fiscal incentive in all things DNDN? I hope the Huber authors are sleeping well at night... Shame on you, there are people Dying with this disease! Ask your self this, if your father, brother or YOU have mCRPC would you want Provenge???

 

Shame on Investors Village/Care to Live people cluttering a lawsuit thread with their own slimy agenda about Provenge. These people were victims of Gold too and hold on to some notion they have a chance to get their money back. This thread is not about the merits or lack of merits of Provenge or how you can get your money back. Your best chance at that is the class action suits. This thread is about employee victims of this company. Start a thread about Provenge if you like but stop deflecting in posts about DNDN. Provenge and DNDN are separate issues.

 

Writing in the March 2012 issue of AUA News (p. 42), Dr. Carl A. Olsson had this to say about the paper published by Huber et al. in the JNCI:

“The authors missed the report by Hall et al that “there was no evidence that leukapheresis led to immunodepletion,” citing literature proving that each apheresis removed less than 1% of the total body pool of 1012 lymphocytes and reporting a normal measured cell count after the third apheresis in all men.3

“Finally, we are all used to the values of interdisciplinary conferences, which usually combine the experiential qualities of urology, clinical oncology, immunology and other disciplines. However, “healthcare analyst” and “investment management” are talents that appear unseemly in major publications.”

3. Hall SJ, Klotz L, Pantuck AJ et al: Integrated safety data from 4 randomized, double-blind, controlled trials of autologous cellular immunotherapy with sipuleucel-T in patients with prostate cancer. J Urol 2011; 186: 877.

 

3. Hall SJ, Klotz L, Pantuck AJ et al: Integrated safety data from 4 randomized, double-blind, controlled trials of autologous cellular immunotherapy with sipuleucel-T in patients with prostate cancer. J Urol 2011; 186: 877.

This was written by Dendreon publication team, this is an example of ghost writing. Hall and others just put their name in order to have more publication. Perhaps they need to be more cautious. Needless to say that Simon, Larry and Alan are all great and respectable Urologists.

Urologists for most are surgeons first and scientists next. There are some exceptions but in general, Urology journals are not comparable to Oncology and or JNCI when it comes to scientific discussions.

There are so many unknowns about Provenge that makes it hard to defend the therapy. Unfortunately, it's leadership are bad too and have a very bad reputation, therefore, can not be trusted. Not communicating the HLA typing data from their trials is only one example of why we can not trust Provenge data and it's leadership.

 

Well Said!

 

Well said!!

 

Another interesting editorial..

"Ms. Huber’s background is financial work for hedgefunds. She is not at all qualified to “approach European regulators”. She has never worked in medical research or ever treated a patient. Prostate cancer patients and doctors that prescribe Provenge think it is great and beneficial treatment. The FDA and Center for Medicare Services completely vetted the Provenge data. Does she think her medical knowledge and medical testing knowledge is better than the FDA or CMS? World renowned oncologists like Dr. Kantoff of Harvard and Dr. Drake of Johns Hopkins have said that Ms. Huber’s immune system depletion theory has no merit at all. I guess she also thinks that her medical knowledge is superior to the collective medical knowledge of over one thousand oncologists and urologists that have signed up to treat patients with provenge. Has Ms. Huber even spoken to one prostate cancer patient that received provenge or one physician that prescribes provenge? Of course not, because she is not at all interested in the truth, she is instead interested in the financial benefit of her former hedge fund co-workers. Ms. Huber’s anti-provenge crusade is harmful to cancer patients."

 

those 35k short shares may not know much about provenge but they must know about the law.

 

35M

 

Phil Kantoff, very nice man, does not know much about immunology, he had less than 5 patients in IMPACT trial and was brought in last minutes to be the first author.
Chuck Drake, good scientist who is advocate of immune therapy not Provenge. Ms. Huber has a right as an EU citizen to approach EMA and other regulatory and or reimbursement agencies and ask valid scientific questions. If there is nothing to hide, no one should be afraid.

 

If that is you who is finally out of here I am happy for you. You are the most knowledgable poster here about what happened in DNDN.

 

Side by side comparison of increase in Overall Survival:

1. Provenge has a medium increase in survival of 4.1 months. Probably (but not officially) 8 months if factoring placebo crossovers to frozen Provenge.

2. Zytiga has a zero increase in overall survival pre-chemo.

3. Taxotere has a 2.4 month increase in overall survival plus serious side effects.

4. MDV3100: The "PREVAIL" study for pre-chemo (the space that Provenge competes in) is still enrolling. Probably 2+ years away from results and approval in that label.

The future for Provenge looks very good indeed!!

 

i have no opinion one way or the other but when someone who is vouching for provenge does not know the word median it does not say much for that persons credibility.

 

In the case of Provenge median means that half the patients got more than a 4.1 month increase in their life expectancy compared to placebo and/or frozen Provenge. In some cases they lived for many years longer than they were expected to.

For all we know Provenge might be a cure for Prostate cancer if given early enough with boosters given periodically.

 

we already know it is not a cure. stop spreading lies. it does not shrink tumors. everyone knows that.

 

“it does not shrink tumors” should be qualified with “as being measured in the IMPACT trial”.

Failure to be detected in an experiment does not equate to effect not existing.

 

it does not shrink tumors. no qualifiers needed idiot. even froehlich would tell you that with no qualifiers.

 

Theodore, you and your care to live cronies are going to lose everything. You have already lost almost everything. Keep riding this company down to 2.