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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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« You Discover It, We Sell It. Deal? | Main | Incomprehension, Out For A Stroll »

July 30, 2007

Avandia's Latest Round

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Posted by Derek

I have to say, I think the FDA vote on Avandia (rosiglitazone) was well done. As those following the story know, David Graham at the agency had been pushing to have the drug removed from the market, but a panel just voted 22 to 1 to keep it, albeit with warning labels and stricter standards for use.

That's as it should be. As mentioned here before, we really don't have hard enough data on the compound's risks yet and whether or not they outweight its benefits. I think that this decision is a grown-up one: to say that yes, rosiglitazone appears as if it may have some cardiovascular risks, but since we're not sure about that, for now it appears that they're risks worth taking. It'll be up to patients and their physicians to make the call.

Would that it always worked this way! Drugs have side effects, how ever much we might wish that they didn't. Some are bad enough to wipe out any benefit, and some aren't. It's a judgement call every time, and I'm glad that the panel exercised some instead of going reflexively with the "no risk to anyone for any reason, ever" mindset.

Avandia may well be taken off the market when more data come in. And if that happens, then we'll know that it was the right decision. But we don't know that yet. How, I wonder, will this vote affect the lawsuits that are already being prepared? Can you sue for being (allegedly) harmed by a drug the FDA just re-reviewed and decided to keep?

Comments (19) + TrackBacks (0) | Category: Toxicology


COMMENTS

1. Jeff Bonwick on July 30, 2007 11:50 PM writes...

What's the drug called again? Rosy Litigation Zone?

Sorry, couldn't resist... ;-)

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2. Roger on July 31, 2007 12:00 AM writes...

Derek,

Are you on Glaxo's payroll. The number one cause of death seen in diabetes happenns to be heart disease. So, now prescribing a pill that could even carry a slight risk of a heart attack to a person already prone to having one makes no sense. These drug companies are pushing Dr's to prescribe these new blockbuster drugs. Glucaphage, Metformin and others are cheaper and don't carry the risk and in many cases work even better than Avandia. This has nothing to do with the safety of the drug. It has to do with GLAXO not being able to loose a 3 BILLION dollar a year drug. So go ahead Drs prescribe a drug that carrys a pretty high risk of heart problems. Who are you Derek?

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3. jesus on July 31, 2007 7:06 AM writes...

Derek,
I noticed are your profile you "worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes.." It is apparent you are on the payroll. Unfortunally people on the drug "avandia" have been mislead by companies, FDA and people like yourself. Are you taking the drug "avandia", if you were your opinon might be a little different.
js

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4. A-non-y-mous on July 31, 2007 7:19 AM writes...

Derek certainly doesn't need a nobody such as myself to defend him, but if one thinks he's on a "payroll", they are misguided and mistaken.

For those that do believe the FDA, doctors, pharma, and the media are in on an Avandia (or other drug) conspiracy, I just started a new medical device company that should put your fears at ease. I'd advise you all to purchase my #1 seller: Tin foil hats.

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5. Petros on July 31, 2007 7:36 AM writes...

Without sifting through all the evidence it is hard to be dogmatic about which is the correct outcome for Avandia. But it is easy for individuals to stoke up concerns about various drugs or treatments.

Note the imapct of Dr Andrew Wakefield's scaremongering over the safety of MMR vaccine in the UK based upon a poor,scientific study.

I concur with the Derek that the decision appears to be the right one, based upon the available evidence.

And it is interesting to note that in the UK concenrns have been raised about the caridovascular safety of Actos as well as Avandia. As one might expect if there are class effects, which the history of PPAR agonist development would sugegsts is probable.

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6. tom bartlett on July 31, 2007 7:49 AM writes...

Derek is right. The FDA is under enormous pressure from law-suit happy lawyers to pull all kinds of pretty safe stuff from the market. Remember Vioxx? Really, they should be more on the other side-- working to make it easier to get more new life-saving treatments out to patients.

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7. NJBiologist on July 31, 2007 7:59 AM writes...

Has anybody been able to figure out where Graham is getting his numbers this time? Is it yet another chart review?

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8. Palo on July 31, 2007 10:01 AM writes...

Almost every possible drug has some benefits and down sides. And that is the only reason the FDA exists. If it was as simple as "let the patients and doctors" decide, then why do we need the FDA? The reason we need the FDA is because patients and doctors, most often than not, cannot decide. The don't have the training and information to decide. I don't know the specifics here, but to have a drug that could create serious problems, and simply say that with labels we make it 'safer', is simply to shift the decision to the people that, most often than not, cannot make that decision.

As derek says:

Avandia may well be taken off the market when more data come in.

then why not wait for the 'more data' to come in before they make a decision?

This solutions simply says the FDA concludes it shouldn't do its job. Then let's get rid of the FDA and we are all free to take whatever pill they offer us. With the proper labels telling us that the pill could be great or could be terribly wrong, of course.

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9. Su on July 31, 2007 10:32 AM writes...

Recently Actos (competitor drug) has been linked to Cancer. Now what if the FDA pulled Avandia and 5 years down the road discovers that Actos has caused cancer in a large population of users who could have been using Avandia with no ill effects? There are some instances when jumping the gun is warranted and some when not.

Logically this is not...enough is not known.

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10. Wavefunction on July 31, 2007 11:01 AM writes...

I heard of a doctor who, outside his clinic, has pasted a printout of recent problems with the glitazones, and has also posted what GSK has to say about them. He tells the patients to make up their own mind if they want to take the drug or not.

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11. Jose on July 31, 2007 11:28 AM writes...

It is time for all prescriptions to come with a waiver that says, "There is no such thing as a damn free lunch. Every drug has risks, period. Suck it up if you want the benefits, and sign on the line."

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12. Devices R Us on July 31, 2007 12:15 PM writes...

If taking Avandia increases slightly your risk of heart attack, not taking it and living with T2 diabetes increases your risk by many more fold. The real question is what are the risks for taking it or not taking it.
There is a big, correctly designed study to ask the very question, lets wait for the results.

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13. Anonymous on July 31, 2007 2:50 PM writes...

A lot of the type 2 diabetics could have prevented their condition anyways, so no sympathy from me. The real problem with our healthcare system is not the safety/efficacy of our drugs, but the lazy Americans who sit around all day, eat potato chips, don't exercise, smoke 2 packs a day, and then want to live until they're 100 and not have to pay for any medication.

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14. Hap on July 31, 2007 5:05 PM writes...

Marketing to large audiences in search of profits leads to two relevant problems. First, advertising tries to promise the sun and moon but in ways for which the advertisers can't be held responsible. Second, the marketing tends to aim at expanding the market to new patients, many of whom may not benefit from it (and thus for whom any risk outweighs the (null) benefits). Further enhancing the problem is the cost of drugs - people are less likely to accept risks as the cost of treatment goes higher (unless there is no other treatment).

Desiring people to accept large risks for your benefit while paying large costs for drugs is a recipe for industry suicide, particularly if marketing money pilfers research dollars and prevents the industry from actually developing products to sell. Blaming your patients is just another line in the suicide note.

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15. Michael on July 31, 2007 8:16 PM writes...

The problem is that the FDA has only limited choices - to leave the drug on the market with warnings or withdraw the drug altogether. The system needs to be more flexible. The FDA needs to have a probationary system of registration for new drugs and those tagged with red flags, and should have the power to require companies to conduct post marketing surveillance studies.
As for the merits of rosi - well, I would be very circumspect about a drug that does great things for your glucose tolerance but increases your cardiovascular risk. The other glitazones may be a better bet. Why take a chance with a suspect drug like this?

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16. Walt on July 31, 2007 9:26 PM writes...


A bigger issue for avandia is actos. Since actos has the same safety profile, lowers TGs (avandia does not) and none of the unwarranted press that avandia gets, many physians are switching their patients to actos. The possible cancer link with actos has not affected the prescribing physians.

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17. Kareno on August 1, 2007 10:40 AM writes...

It sounds like nobody really cares if Pharma discloses all the risks, provided studies are carefully done which will eventually come to a conclusion, which may or may not have effected how docs prescribe. And that is why there is so much litigation today, because Pharma is hiding data to get the drug on the market as fast as they can to make the billions. If I'm a doc, I want them to tell me everything, especially that a drug whose main benefit is to control blood sugar which helps lower CV risk, actually increases CV risks by 50%. Takeda provided the 10% increase CV risk with Actos to the FDA pre-approval. GKS did not. I also want to know that if glycemic control is an issue, that Actos is a better glitizone. I don't give a rat's ass if GSK loses money as long as I save a few lives. I want to see how Avandia sales fare, and then ask the question, what does a little knowledge do? That is why GSK is pissed. It has nothing to do with statistical purity. I wonder if a vast majority of docs who prescribed Avandia before Nissen yelled are happy to have been given credit to make a rational decision. The doc who pasted up the media stuff is a cop out douche bag who would rather wallow in his/her criticism of the media than bask in the light of information. It's his/her job to help the patient sift through the crap, but don't hide your head in the sand by shirking your duty, which is to your patient and not to Pharma's desire to have the facts etched in stone, especially when the etching may be a tombstone

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18. Clark Kent on August 1, 2007 1:40 PM writes...

A few points from the FDA meta-analysis:

1) Avanida only raised the CV risk when compared against placebo. Against active controls it showed no increased risk. Meaning that Glyburide and Metformin must carry the same CV risk.

2) The risk was more pronounced in the short-term studies (6 months or less), as the studies ran longer (1-4 years) the magnitude of the risk decreased (maybe Avandia does reduce CV risk, but it may take awhile to reverse the effects of diabetes)

3) The risk was greatest when Avandia was co-dosed with other drugs, most notably nitrates and insulin. When given to drug naive patients, there was no increased CV risk. Maybe its a drug-drug interaction thats the problem, and just not dosing it in patients taking the other drugs will eliminate the problem.

4) The same meta-analysis that showed a 40% increase in heart attacks showed a 50% decrease in strokes for patients on Avandia. The doctor and patient should decide how to balance this risk/benefit.

5) In the ADOPT clinical study which compared Avandia, Metformin and Glyburide, Avandia had a slightly higher incidence of CV events than Glyburide, but a significantly lower incidence of death than Glyburide. Metaformin and Avandia were not significantly different on either risk. I don't know about you, but I'd trade a higher risk of heart attack for a lower risk of death.

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19. Robert Guetterman on April 9, 2010 9:21 AM writes...

i started on Avandia at a body weight of 333 and after avandia I acuired empachema im on oxygen 24/7 I am living proof Avandia needs to be taken off the market I now way 425 I was taken off Avandia in 2007 it has been a struggle after having gained 50 lbs of just water weight while on avandia

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