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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline

« Who They? | Main | Roche Starts to Manage Things »

April 14, 2009

Dendreon's Revenge?

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Posted by Derek

Post updated below - DBL Dendreon is a company that's really been through it, as have their investors. Many will remember the upheaval back in 2007, when the company showed what they felt were impressive results for their autologous prostate cancer immunotherapy Provenge, got a favorable reception from the FDA's advisory panel, but were then hit with an "approvable" letter asking for more data. (Here are three posts on that: before, during, and after).

Well, the company is back with more data, in 512 patients. And initial reports are that the numbers look good. They're doing a conference call as I write, so we'll know more shortly, and I'll update this post as things become more clear.

Update: Hmmm. On the conference call, the company has declined to present any numbers, saying that it's bound by a blackout requirement for its presentation at the American Urological Association on April 28th. Their main statement seems to have been that the drug met its primary endpoint, reducing the risk of death compared to a placebo. There are a lot of other questions about Provenge - whether it slows the progression of prostate cancer or not, for example - but survival is presumably the bottom line. That was the main focus of the whole trial (as opposed to the cancer-progression endpoint of their smaller, earlier one).

So we'll see at the end of the month how impressive the statistics look. The market's reacting well to the news, although you could argue that the stock has pulled back a bit. It closed yesterday at 7 and change, traded over 21 during the morning, and is around 17 now. (Of course, some of that pullback could be from people giddily selling their shares on the news, just as some of the spike could well have been some people rather less giddily covering their short positions).

Comments (17) + TrackBacks (0) | Category: Business and Markets | Cancer | Regulatory Affairs


COMMENTS

1. Ty on April 14, 2009 9:47 AM writes...

this was an unnecessary trial. writing was on the wall 2 years ago. can DNDN sue FDA for the financial damage its questionable decision has caused? it should amount to hundreds of millions of dollars...

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2. Yt on April 14, 2009 10:39 AM writes...

They can of course try to sue the FDA, but the trial wouldn't get them anywhere. The FDA is fulfilling their role as a regulatory institution.

Unless they can show there was a motive in the ruling, other than validating statistically (and practically) significant clinical efficacy, then they don't have much of a case.

And just what writing on the wall are you talking about exactly? This drug has been one big roller coaster since its phase II trials.

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3. Ty on April 14, 2009 10:45 AM writes...

may be the joke sounded too serious..

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4. Yt on April 14, 2009 10:52 AM writes...

Hah, sorry. Hard to decipher what exactly is a joke after Wyeth v. Levine

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5. Andrew on April 14, 2009 11:53 AM writes...

wow the stock is up 150% percent!

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6. Muruga on April 14, 2009 12:47 PM writes...

Provenge would be the first cancer vaccine (cancer immunotherapy), if at all approved by FDA. It was not surprising that FDA was too cautious, issuing an approval letter, asking for more data two years ago for a first-in-class therapy. The concept, which is better understood now, seems to work. Hope to see a green signal from FDA for marketing!

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7. CMC Guy on April 14, 2009 2:32 PM writes...

Muruga may be partially correct that was some over caution by FDA for first in class/mode of therapy but there apparently are other considerations that reflect on how FDA operates. The earlier studies targeted progression endpoints as surrogates but unfortunately fell short to meet them as designed (from company perspective cheaper and faster and assume had suggestion it would work). If one fails to answer the question(s) experiment supposed to one usually expects to do more investigations but submitted anyway. Post-hoc analysis of combined data gave (strong?) suggestion of survival benefit which is ultimate goal but was not even secondary study endpoint so studies not powered to adequately demonstrate (so not question asked). Such statistical analysis are always "less secure", particularly with the stringent statistic dogma that FDA seems to follow, so again addition data not unanticipated. The "approvalable letter" at the time offered a pathway for gaining approval but was a clear set back.

Even with "failed trials" and statistical vagueness I wish FDA could have accepted the data based on "probable benefit" because the overwhelming need of the targeted patients and the excellent safety profile that was shown. With a bureaucratic mindset there does seem to be lack of focus on the patients who need new treatments and the US system has no "conditional approval" mechanism which would have allowed greater access while continuing to get the supporting data (not to be confused with drugs that are "approved with conditions" which typically involve P4 studies looking at AEs not efficacy).

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8. Damien Bove on April 15, 2009 2:53 AM writes...

I must admit when I hear of people suing the regualtors for a decision it makes me cringe, the regulators should and do pursue these issues with the nature of an academic institution, they should be removed from the markets, and focus on science and safety. They are answerable to the people not the pharma industry.

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9. Aloha on April 15, 2009 8:48 AM writes...

Roche has a music video out. Is this the greatest ad campaign ever or the worst?

http://roche.cnpg.com/video/flatfiles/843/index.aspx

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10. Don B. on April 15, 2009 9:14 AM writes...

How many patients died from prostate cancer that could have been treated in the last 2 years????

Before the PSA test came along, I lost many operating (compared to setting in an office) organic chemists/friends/colleagues to the disease.

With the PSA in place many are living after a high PSA result & resulting surgical intervention.

The robotic surgery of ISRG (no position in the stock) has been a tremendous advance.

Don B.

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11. jwint on April 15, 2009 10:13 AM writes...

The lawsuit "joked" about by Ty and "cringed" about by Damien, should have nothing to do with Pharma. The complaint should issue from those who suffered needlessly and were denied effective treatment: the same ones to whom the FDA is responsible. Clearly courage is needed both to approve new drugs as well as to disapprove drugs.

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12. qetzal on April 15, 2009 10:24 AM writes...

I think CMC Guy's point about conditional approval may be particularly relevant. As I understand it, FDA's accelerated approval program was supposed to fill that role. In practice, it doesn't seem to quite do that job.

I suspect one problem is that once a drug is granted accelerated approval, FDA has been unwilling (or perhaps politically unable?) to force drug co.s to do the agreed follow-up studies, or to pull a drug that didn't live up to expectations. (Does anyone know of any drug that was granted accelerated approval but was later pulled for failure to show efficacy in the non-surrogate endpoint?)

So maybe FDA feels that granting accelerated approval is de facto no different than regular approval, and is unwilling to use that in the conditional manner CMC Guy advocates.

Whatever the reason, I agree FDA should have a true conditional approval program that really works as intended. If accelerated approval isn't viable in that regard, they should set up something new.

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13. DrSnowboard on April 15, 2009 10:44 AM writes...

@12
http://www.accessdata.fda.gov/scripts/cder/onctools/Accel.cfm#SubpartH suggests 27:5 clinical benefit not established : established?

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14. Tim W. on April 15, 2009 3:04 PM writes...

It's good to see some powerful validation of the basic science -- autologous vaccine + cellular therapy. Now maybe fundraising will be a little easier for phase III companies like TVAX Biomedical.
http://www.tvaxbiomedical.com

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15. qetzal on April 15, 2009 9:22 PM writes...

DrSnowboard,

Nice link - thanks! Though I confess I'm not sure what point you're making (if any) beyond citing the raw numbers.

Interesting to note that only 2 accelerated approvals were granted after 2004. Also, what happened to the 25 where clinical benefit was never established? Looks to me that many (most? all?) still have approval despite not having proved benefit.

If so, it's not functioning as a true conditional approval system. There's no true condition - once you get accelerated approval, you apparently get to stay on the market regardless of whether you ever demonstrate clinical benefit.

I don't know why that is, but I can imagine that some at the FDA would see that as a failed approval system, and would not want it used any more.

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16. Dan on April 24, 2009 7:22 AM writes...

Published on: www.psa-rising.com
The Unreachable Unavailability of Provenge
*FDA’s mission statement: To promote and protect public health.
Terminal patients are those who are not expected to live due to usually illness such as advanced prostate cancer (cT3). If the patient has 6 months or less to live, those patients are considered terminally ill. Regardless, if a patient is terminal, they are without a cure or tolerable treatment for their illness presently. Since such patients will likely die in a short period of time, treatment options, even if they are not entirely unproven, are often desired by such patients.
This is understandable, because at such a severe stage of illness, such as prostate cancer, possible extension of their lives with comfort is worth it to them, regardless of lack of evidence of proof of whatever treatment that may be advantageous to them regarding these issues. The FDA, however, claims authority on the treatment options of such patients, although that administration has proven itself over the years to be rather inadequate with its frequent drug recalls and black box warnings, and they do these things only under pressure from the public, usually. Reform has to start somewhere at some time.
Prostate cancer is a rather frequent occurrence- with between 10 to 20 percent of men predicted to acquire the disease during their lifespan, resulting in about 30,000 deaths a year from this disease of the one million men. Furthermore, out of all cancer types more are dying from prostate cancer now than other cancer diagnoses.
For those unaware, there are different stages of prostate cancer, and the more severe the prostate cancer cases are which is determined by such methods as bone scans and Gleason’s scores, which is a score that assesses prostate tissue after it is biopsied and if it is determined that the stage of cancer is severe by this and to estimate proper treatment options if proven to be malignant.
Typically, the initial suspicion of prostate cancer is determined by the results of what is called a PSA blood test, as PSA is a protein produced by prostate cancer cells. If the PSA blood test is above normal limits, a prostate biopsy is performed to determine and confirm not only the presence of cancer, but also the severity of the disease on such a patient.
Yet fortunately, and as you will read, innovation still exists in medicine. A few years ago, a small Biotechnology company called Dendreon was working on a conceptually new treatment for the worst prostate cancer patients, and this treatment therapy created by Dendreon was named Provenge. Provenge is the first immunotherapy biologic treatment for the progressed prostate cancer patients, and has proven to be a very novel and innovative treatment option for advanced prostate cancer patients who are terminally ill.
Usually, these patients are unresponsive to usual treatment methods for prostate cancer, and are left with chemotherapy as their only treatment option at such a traumatic stage of prostate cancer. Understandably, most patients at this stage refuse treatment entirely, largely due to the brutal side effects of such chemotherapy treatments as taxotere. The immunotherapy method developed by Dendreon required the removal of white blood cells of the diseased patient and, after altered, are re-injected into this patient now designed to attack what is called PAP, which is on prostate cancer cells only.
This treatment required only three such injections in a period of six weeks. This resulted in life extension twice that of chemotherapy treated prostate cancer patients of this severity, and without the concerning side effects of chemotherapy. The medical community and survivors of prostate cancer were elated and waited with great anticipation for access to this treatment method.
Fortunately, as the years passed, Provenge, by 2007, had convinced others of its safety and efficacy in its benefit for severe prostate cancer patients. This caused great joy to such patients and their families. Perhaps greater elation was experienced by the caregivers and specialists of such a disease, such as Urologists and Oncologists who treat such patients.
While Provenge was on fast track status at this time at the FDA, the FDA panel thankfully recommended with clarity the approval of Provenge based on its proven and substantial efficacy and safety demonstrated in its performance in past trials. The FDA announced this to the public in the early Spring of 2007, I believe.
Now for the bad news: With great shock and surprise, the FDA agency rejected the approval of this great treatment for very sick patients due to, they said, ‘lack of data’ in May of 2007. This contradicts their favorable opinion of Provenge weeks before delivering this terrible news. Especially when one considers the FDA Commissioner is a prostate cancer survival himself!
Soon after this judgment was passed by the FDA, conflicts of interest were discovered by others. For example, a member of the FDA agency who was evaluating Provenge, Dr. Scher, was found to have a financial commitment to a future competitor of Provenge that was being produced by a company called Novacea, and this company had signed a co-promotion agreement with Schering with this similar prostate cancer drug being developed by this company. Dr. Scher never disclosed this conflict during the approval process of Provenge.
As it turns out, this anticipated prostate cancer drug made by Novacea was discovered to have serious flaws, and Schering pulled out of the agreement with Novacea. In addition to this incident and before May of 2007, baseless letters were anonymously delivered to the FDA stating negative qualities about Provenge that were without Merit and speculative claims about the treatment.
Yet overall, the disapproval by the FDA of Provenge angered many, and a newly formed advocacy group called Care to Live filed a lawsuit against the FDA for their clear lack of protocol or knowledge about such complex treatment agents as Provenge at the end of last year.
Terminal patients, I surmise, desire comfort during their progressive disease that has placed them in the last chapter of their lives, and certainly should have a right to choose any treatment that possibly could benefit them. At this stage of such a patient, one could argue, safety of any treatment option is not of concern to these patients, because they are going to die anyway. Yet the FDA, with reckless disregard and overt harshness for these very ill patients, ultimately harmed others more by not approving Provenge with deliberate intent.
The FDA does in fact presently have the ability to grant what is called conditional approval for such treatment methods as Provenge, and why they have not expanded this approval process to all terminally ill patients remains completely unknown.
What is known is that they are harming those they pledged to protect so long ago by depriving such patients in need of treatment, as no other options are viable presently that are as safe and effective with great tolerability associated with Provenge.
So now the FDA appears to be a bought, corrupt, and incompetent administration without loyalty and dedication to the public and its health. This needs to be corrected in any way possible for the lives of others.
A terminally ill patient has a personal right to obtain and access such treatments upon their own volition as well as the discretion of their doctor, just as a terminally ill patient is granted an individual right to die, if they choose to do so. It is an individual decision in such cases that should be void of interference from others.
“Politics is the systematic organization of hatreds.” --- Henry Adams
Dan Abshear
Author’s note: What has been written is based upon information and belief

Permalink to Comment

17. Bill on July 16, 2013 2:52 PM writes...

Wow, Time warp. Hey, wake up, it's 2013.

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