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PHARMA: Wall Street, Cancer, and the FDA: A Cautionary Tale by Maggie Mahar

Maggie Mahar  writes on healthcare, economics and public policy. Her work has appeared in The New York Times, Barrons, Institutional Investor and may other publications. A regular contributor for THCB, her most recent book is "Money-Driven Medicine: The Real Reason Healthcare Costs So Much." She was recently named a fellow at The Century Foundation.

Only in America do physicians
who evaluate new drugs need bodyguards.

You may have read about the
brouhaha surrounding Provenge, a vaccine designed to extend the lives
of men suffering from late-stage prostate cancer. In March, a Food and
Drug Administration (FDA) advisory panel voted 13 to 4 to recommend
approval. The next day, shares of Dendreon, the drug’s sponsor, doubled.

But shareholders did not celebrate
for long. Two of the dissenting votes were cast by the panel’s two
prostate cancer specialists: Sloan-Kettering’s Howard Scher and the
University of Michigan’s Maha Hussain. And they did not just vote
“no”—following the hearing, both wrote to the FDA arguing that
Dendreon offered no solid evidence that Provenge works.

The FDA listened. And in May
it told the company it wouldn’t approve the drug until it had   more
data. That is when the two oncologists began receiving threatening e-mails,
phone calls, and letters. Many were anonymous.

No doubt much of the hate mail
came from investors who had watched Dendreon’s shares climb from $5
in early January to $25.25 in late March—before plunging to $3 and
change. One Alabama shareholder expressed his feelings on his MySpace
page, where he asks “Hey, Hey, FDA, How Many Dads Did You Kill Today?”
while images of Hussain and Scher flash across a backdrop of crooked
crosses. Mozart’s “Requiem” plays in the background.

The response illustrates how,
in a money-driven health care system, those who view health care as
a profit center strive to dictate social policy. From their point of
view, the FDA should approve any product that Wall Street finds attractive—and
then let the market decide whether or not the drug is both safe and
effective. What they ignore is that, unlike other consumers, sick patients
are not in a good position to comparison-shop. They must rely on the
doctors and scientists who serve on FDA panels to sort through the hundreds
of offerings that drug makers hope to bring to market. For even if a
drug makes it to Phase III trials, this is no assurance that it is safe—or
that it will work. Indeed, a recent study shows that fully 40 percent
of new drugs fail in that final stage of testing
.

So far, the FDA has not bowed
to investor pressure regarding Provenge, but the e-mails and phone calls
were too menacing to be ignored. When Hussain and Scher attended the
conference of the American Society of Clinical Oncology last month,
both asked for extra security guards. At that point, Hussain began wondering
whether she should continue as an FDA adviser.

Patients also protested the
FDA’s decision. Many had pinned their hopes on Provenge because it
is one of a group of new cancer drugs under development that uses the
patient’s own cells to create a vaccine designed to mobilize the patient’s
immune system to attack the cancer. The notion that the body might “heal
itself” is enormously seductive. For more than a century, oncologists
have dreamed of such a solution. But thus far, as Dr. Steven A. Rosenberg
of the National Cancer Institute confirmed in an e-mail to me last week,
“there are no therapeutic vaccines that have been shown to be effective.”

This is not what patients want
to hear. But while many were crushed by the FDA’s decision, patient
advocates such as PSA Rising disown the hate mail. "Folks, this is not grassroots
cancer patient activity, it’s . . . naked grassroots investor activity,”
wrote Jaqueline Strax, the editor of PSA Rising, in her newsletter for
prostate cancer survivors. “Ironically, some investors have whined
that prostate cancer patients are not helping THEM on behalf of Dendreon.” Roman">

Meanwhile, shareholders charged
that Sloane-Kettering’s Scher nixed the drug because he is the lead
investigator for a rival product. To drive this point home, earlier
this month Provenge activists
raised $24,000 on the Dendreon message
board at Investor Village to buy a half-page ad in the Washington
Post
headlined
“Prostate Cancer Victims Face Needless Suffering and Premature Death.”

Could this be true? Knowing
how much misinformation swirls around any new cancer drug, I decided
to take a close look at the transcript of the FDA hearing and find out
more about the scientific evidence
behind Provenge. 

This is when my skepticism
turned to shock. First, I learned that Dendreon has done two clinical
trials attempting to show that Provenge slows the progress of the cancer.
And that both failed. That’s right—the studies offered absolutely
no proof that the drug put a brake on the disease.

“It’s not clear why the
FDA panel was even voting on the drug—Provenge had already been check-mated,”
says Paul Goldberg, who broke the story by printing Scher’s letter
to the FDA in The Cancer Letter, a weekly newsletter about the
politics of cancer. . . .

In the meantime, “the stock
has become the momentum trading vehicle of 2007,” TheStreet.com’s
Adam Feuerstein wrote earlier this month. “A stock that will be pumped
and dumped based on the flimsiest of rumors and lowest-common denominator
reporting.” 

Inevitably, the Wall Street
hype spills over into the mainstream media, where dying patients, willing
to grab at any thread of hope, read about a drug and begin to believe
that, if they could just get access to the “newest new thing,” it
might save their lives. (In fact, even the company claims only that
the average patient might win an extra 4½ months.) Those who
“pump” the stock do patients a cruel disservice.

Ultimately, Scher and Hussain
were not the only ones who would be  intimidated by the Wall Street community.

I’ve written the full story of Provenge, discussing how it passed
the FDA panel, and whether individual patients should have the right
to gamble their lives on an unproven drug at http://www.tcf.org

Read the extended version of the story at http://www.tcf.org/Publications/HealthCare/healthbeat.pdfPlease return here to comment

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Carey D.
Guest
Carey D.

Any more comments? You got shut down with your silly article and lack of factual data to back up your position. IMO I did not mean for a “personal attack” on you. If I had, I would have said: you “were” rather than “I think” as I was trying to realize and understand why you would take such a position without being educated on the statistics. I however think Walldiver summed it all up fairly well why you psotion yourself as you did.(see below) I would seriously like to see an intelligent rebuttal to the real facts such as those… Read more »

bev M.D.
Guest
bev M.D.

Uh, Maggie; I wouldn’t want to be called a cold lonely woman either (wtf??!!), but in the name of using precise terminology, there is no cure for prostate cancer with distant metastasis – not all prostate cancer. I know you know this. Interestingly, Lance Armstrong had practically the only solid cancer that CAN be cured when widely metastatic – testicular – but he is still a lucky man.

biker88
Guest
biker88
Maggie Mahar
Guest
Maggie Mahar

Bev M.D.– Thanks–you make the best point about why investors are inevitably biased, like anyone else with a financial interest in the outcome of a FDA decision. I’d urge everyone to look at http://www.aamc.org/research/coi/science.htm on conflict of interest. I also think that FDA reform is coming, and that ultimately physicians and scientists with a financial interest will no longer be sitting on panels. The piece on hospital architecture (on the same site) also is interesting. I can see the argument that private rooms make medication mix-ups less likely. But I’m still concerned that too much money is being spent on… Read more »

bev M.D.
Guest
bev M.D.

Carey D.; The reason why investors should have no say in this process, among other reasons, is found in the American Association of Medical Colleges link I cited above: “The (scientific) evidence suggests that self interest has a tendency to bias independent judgement in unconscious ways.” You may fairly argue that the two docs are in no better position than investors due to their own purported conflicts of interest. But don’t set investors up as people with a right to sit at the FDA’s conference table. Much less threaten the people who do sit there. I agree the FDA has… Read more »

Carey D.
Guest
Carey D.

Maggie, You seem to be a great writer. You are so wonderful. However you seem to only be trying to prove the only reason people are actively trying to change the “non-approval” of provenge is because they are all bitter investors. “I’d also note that once again, it turns out that many of the most vociferous critics of the FDA decision are not patients, but investors” M.Mahar So what? Investors are more informed than any other group when it comes to the many aspects of Provenge and it CR letter. The investors are not just investors, they are among others… Read more »

bev M.D.
Guest
bev M.D.

Maggie;
I found a link to the American Association of Medical Colleges which cited a symposium on the “science of conflict of interest”. It won’t solve everyone’s assertions on this particular issue, but it does indicate the profession is taking notice. Change will no doubt follow, after a lot of kicking and screaming.
http://www.aamc.org/research/coi/science.htm
In addition, Maggie, regarding the issue of private rooms, which you and I both thought wasteful, here is information from the same organization that has changed my mind:
http://www.aamc.org/newsroom/reporter/june06/patients.htm
Data is everything; not just throwing around opinions.

tallwhenhorizontal
Guest
tallwhenhorizontal

Here are the main points that Maggie can’t address inteligenly. 1)Missed end points have nothing to do with Provenge’s FDA review. The FDA knew about the failed end points but still encouraged DNDN to file the NDA and gave it fast track priority. Provenge was to be judged on survival data. 2)The FDA appointed a panel of expert with great expertise in oncology, immunology, statistics etc… voted overwhelmingly to approve Provenge 13-4 efficacy for survival and 17-0 safety. 3)This is the first time in its history that the FDA went against the apointed panel recommendation for a drug adressing terminaly… Read more »

tallwhenhorizontal
Guest
tallwhenhorizontal

Hang it up Maggie, you are on the wrong side of the argument. You have no conterpoints to the very reasoned arguments that a few of the posters have put in front of you. My total investment in DNDN at the height of the PPS was less the 1% of my portfolio. I explained to you my interest in Provenge, but of course you chose to ignore that and again you refuse to respond to my main question / point. It is apparent that you have no interest in intelligent debate. Wall, Thank you for your contributions to this discussion.… Read more »

walldiver
Guest
walldiver

Maggie, from your last couple of posts it appears that this subject is starting to push your emotional buttons. Perhaps the oncologists in the thread who weighed in on the side of Provenge were the tipping point. To address a couple of your points: when Dr. Fleming strongly came out against Iressa approval for third-line non small-cell lung cancer (NSCLC) back in 2002/03, he did have a strong biostatistical case. The ODAC panel had recommended approval based on the 10% objective response rate (ORR) surrogate endpoint in one or two single-arm trials. The ORR was much lower than Astra Zeneca… Read more »

Maggiemahar
Guest
Maggiemahar

Let’s start with The Cancer Letter. No, it’s not Barron’s or The New York Times. Barron’s and The New York Times turn to The Cancer Letter as an expert source. See for example, the Times quoting The Cancer Letter in this story: ANDREW POLLACK, “Studies Show Anemia Drugs May Harm Cancer Patients”, New York Times, February 27, 2007, Link: http://www.nytimes.com/2007/02/27/health/27drug.html?em&ex=1172725200&en=b255f2891d666d3c&ei=5087. I’d also note that once again, it turns out that many of the most vociferous critics of the FDA decision are not patients, but investors (tallwhenhorizontal). To be fair, some physicians also feel that FDA was mistaken. (Though most haven’t… Read more »

tallwhenhorizontal
Guest
tallwhenhorizontal

Maggie, As expected you didn’t answer my main question. Why I should beleive you rather then 17 people that are far more skilled then you are in imunotherapy, oncology and statistics that voted 13-4 for efficacy and 17-0 for safety??? I even add flemings and make it 13-5…Why? You say that the panel composition was to blame for the positive vote. Who would be more expert on judging an imunology drug, imunologist or oncologist with an agenda to protect their turf? Here is an article from the NY times that illustrate the foolishness of your argument. **** 2 potent cancer… Read more »

Tony F
Guest
Tony F

1. AIPC patients are typically elderly TERMINAL cancer victims with an approximate 18 month expected life-span and often other compounding illnesses. 2. SURVIVAL trumps all surrogate endpoints in clinical trials as several oncology meetings this year have espoused which is a substantial CHANGE from the “old” ways of looking at cancer treatments (chemo) and their results such as TTP. 3. IMMUNOTHERAPY cancer treatment signs and symptoms appear to be significantly different from CHEMOTHERAPY treatments. Our nations best and brightest–including Federal government physicians and researchers–are currently recommending that IMMUNOTHERAPY be assessed differently from Chemo… something that is NOT being done presently.… Read more »

Chuck Bennett
Guest
Chuck Bennett

Maggie, I wanted to respond to several flaws in your logic that exemplifies the problem with provenge. I am not a shareholder in the maker of provenge. I am a physician and the MD’s I know who are familiar with provenge feel, like those on the FDA panel, that it is safe and effective. Benign immunotherapy like provenge, as a part of combination therapy is almost certain to become the next dramatic evolution in standard of care treatment for cancer patients. Regardless of what the good Dr. Rosenberg emailed you I would suggest you peek at the dramatic data presented… Read more »

Maggiemahar
Guest
Maggiemahar

Thanks for the comments. Tall when horizontal points out that Spike and I are not statisticians. I have studied statistics, and it’s obvious that Spike also has real knowledge of the subject. But let’s go back to what Fleming, a biostatistician with a national reputation says. (See my long response to Walldiver on July 25–Fleming also wrote a long letter to the FDA saying that it should not approve Provenge without further evidence.) What is signifiant, I think is that Fleming actually Has Prostate Cancer–which gives him quite a bit of credibilty in my mind. One would expect that, as… Read more »