Wednesday, September 16, 2009

Interesting NYT Cancer-Candidates Story. . . .


Do go read it all, right here, but Gardiner Harris has an excellent piece in The New York Times this morning. It asks whether big pharma is just not coming up with enough "good" new cancer drugs, or whether the FDA's cancer-candidate czar is being a too-tough grader:

. . . ."The industry is not producing that many good drugs, so now they’re looking for scapegoats in Rick Pazdur and the F.D.A.," said Ira S. Loss, who follows the drug industry for Washington Analysis, a service for investors.

In 10 years at the Food and Drug Administration, Dr. Pazdur, 57, has helped to loosen approval standards for cancer medicines and made it easier for dying patients to get experimental drugs. But he demands that drug makers prove with near certainty that their products are beneficial, a requirement that he repeated at a public advisory hearing on Sept. 1 in the slow, loud tones of someone disciplining a dog. After he spoke, the committee of experts voted to reject both drugs. . . .

"You can’t win in this job," Dr. Pazdur said in an interview in his office. "If you approve a drug, they accuse you of lowering standards. And if you don’t approve it, you’re the worst thing since the Nazi death camps and should be killed. . . ."

What do you think? [An image of Schering-Plough's ten-year old cancer drug Temodar, appears at right.]

3 comments:

Anonymous said...

Totally off target but, did you see this old CafePharma note:

Here is the story so far http://www.brandweek.com/bw/news/spo..._id=1002199768

Now, this letter has been published in BrandWeek:

"March 27, 2006

Regarding the article "Bad Medicine" (Brandweek, March 20), your story does great injustice to our CEO and chairman, Fred Hassan.The story unfairly suggests that during his time leading the former Pharmacia Corp., Fred may have been aware of or even encouraged the improper promotion of a growth hormone product by others in the company. The story also makes the baseless insinuation that Fred may have been motivated in encouraging such promotion to increase the value of the company in advance of the acquisition of Pharmacia Corp. by Pfizer in 2003.

Much of this is apparently based on a few words scribbled by Fred at the top of an unsolicited letter from a "Longevity Center" in which Fred requests colleagues to follow up and acknowledge the correspondence.

I can say from my personal experience that Fred routinely puts this kind of notation on dozens of documents each day. He is diligent in striving to assure that every piece of external communications to him gets an appropriate response. It is preposterous to me that this routine action by a diligent and honorable CEO should be framed as some signal to others to do something inappropriate.

I am especially disturbed by the story and its insinuations because Fred Hassan is a CEO who works to embed business integrity into the DNA of every organization he leads. I have seen this first hand at Schering-Plough, where Fred has been deeply engaged in driving a compliance and business integrity program that has become a model for other organizations. Fred is relentless in impressing upon his colleagues that long-term success must be based on doing the right thing for stakeholders, and he leads by his actions and example. The idea that Fred would tolerate, much less encourage, inappropriate promotion of medicines is implausible, as is the idea that he would in any fashion seek to artificially inflate the value of a company that he leads.

By publishing such unfounded insinuations and allegations about a person of such demonstrated integrity, Brandweek does damage to its own reputation.

Brent Saunders svp, Global Compliance and Business Practices Schering-Plough Corp.

Editor's note: The story was not "based on a few words scribbled by Fred," as the writer suggests. Rather, it was based on four lawsuits, several hundred internal documents from Pharmacia, and interviews with eyewitnesses. It was also based on the account of Pfizer, which has admitted in court that Pharmacia distributed Genotropin for anti-aging purposes. Pfizer's own 10-K filing of March 1, 2006, states that those sales are now under investigation by federal authorities. The story made no claims regarding Hassan's personal knowledge of these events. Hassan and his representatives were invited on nine separate occasions, beginning in January, to tell their side of the story. They declined to do so, citing a confidentiality agreement. "

This story is "a grower"!

Anonymous said...

Yes and No.

I agree that it's likely that in regulating cancer drugs you are in a no win situation. I think that industry commonly attacks the FDA as being too cautious whenever drugs don't get approved. I've seen it happen multiple times. For example I remember modafinil, a drug approved for narcolepsy which was studied for ADHD and there was an FDA advisory committee where it was turned down because it was causing Stevens Johnson Syndrome in children, (multiple possible and a probable case in only I think 900 children). Likely because children formed 16 times as much of a potentially toxic metabolite as adults. SJS causes skin and mucus membranes such as in the mouth, GI, tract, inner eyelids, vagina, and urethra to die and is incredibly painful with a 10% death rate. Plus it didn't even work that well in ADHD whereas stimulants work very well. Now there's a BIG HUGE BOLDED WARNING in the labeling not to use in children due to SJS, (Do read how strongly worded it is - find the labeling say at Drugs@FDA and search on Warnings) but afterwards there were articles on the FDA being too stringent with quotes from the company in the NY Times saying it was just a rash.

Now modafinil is prescribed off label for many things including ADHD, Cognitive Enhancement, Parkinson's Dz, and Jet Lag; and the company has been fined over $400 Million for off-label promotion.

As for cancer drugs if you approve something that doesn't work you may deny people the chance at something that does. Plus you may prevent development of drugs that work in the future as patients say why should I take the chance of a placebo or an inactive drug when there's something approved.

In the last few years however there have been approvals based not on survival, which is the sine quo non for CA drugs, but there have been drugs approved based on surrogate markers such as shrinkage of tumor size without showing that it actually extends life or improves quality of life (which they might actually make worse). Plus for CA drugs that have been approved under fast track approvals where confirmatory evidence is supposed to be provided in phase IV trials post approval we have seen based on Congressional inquiries that they are almost never done.

Salmon

Anonymous said...

Speaking of interesting news stories yesterday there was a story on NPR regarding a woman who was the first patient in the US to have a type of eye surgury to correct her blindness.

Her corneas were so scarred that they wouldn't let any light through. What they did is removed her canine (eye) tooth and extracted the nerve. They then cut open her eye and placed a tube through the cornea to let light through. The reason for the tooth nerve is because they used it as an anchor to prevent the loss of the tube. It seems this takes much better than other types of tissue. It worked and they described the tube darting around as she would look at different things.

The reason I mention this is because the blindness was due to Stevens Johnson's Syndrome. When the inside of the eyelids are scarred from an episode they scratch the cornea as you constantly blink to wet your eyes. This results in incredible pain and eventually blindness. I had decided to not mention this type of complication when I wrote the previous post but considering the temporaneous nature of the article reconsidered.

I think that it's important to remember that drugs that kill people (SJS, pulmonary arterial hypertension, cardiomyopathy, hepatotoxicity, cardiac valve disease) not only kill people but hurt and permanantly maim many more people.

For years at work I heard that drugs that kill people are not appropropriate for illnesses that don't kill people. I no longer believe that as I think it's likely many drugs kill people and if we used this standard we wouldn't have drugs (e.g. aspirin or Tylenol and fever). I now think that rare deaths or serious complications (e.g. > 1:25,000 are inevitable and must be lived with, although compensation and care must somehow be provided.)

What I have problems with is things that may not be so rare and that are extremely serious that are covered up and there is misleading labeling and advertising not only to cover things up (and I include in covering up intentionally inadequate and misleading labeling so that damages cannot be mitigated) but also to induce purchases of drugs that are marginally or completely ineffective in the diseases they're being pushed in.

Salmon