Panaceia or Hygeia

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Posts Tagged ‘sanofi-aventis’

Pfizer and Sanofi Join Merck in Abandoning Obesity Drugs

Posted by Colin Rose on November 9, 2008

Pfizer and Sanofi Join Merck in Abandoning Obesity Drugs

By Jim Edwards

November 5th, 2008 @ 6:25 pm

For those of you hoping that America’s obesity crisis could be solved with a pill, think again. Pfizer announced late Wednesday that it is scrapping its anti-fat drug, the as-yet unnamed “CP-945,598,” for essentially political reasons. Sanofi-Aventis today also announced that it was ending its trials on Acomplia/Zimulti, an obesity pill that was approved and then yanked in Europe. And Merck a couple of weeks ago pulled its fat pill taranabant, from its pipeline.

Pfizer’s statement contained an interesting mystery. It said there was nothing wrong with the compound, but they were booting it from the pipeline because they couldn’t be bothered to navigate the bureaucracy required to bring it to market:

Pfizer believes that the CP-945,598 compound has the potential to be a safe and effective treatment for weight management. However, the Company has decided to discontinue the development program based on changing regulatory perspectives on the risk/benefit profile of the CB1 class and likely new regulatory requirements for approval.

“While confident in the safety of the compound, we believe that this is the appropriate decision based on all available information regarding this class of agents, as well as recent discussions with regulatory authorities,” said Martin Mackay, president, Pfizer Global Research and Development.

Really? The company has an effective drug but won’t attempt to sell it — clearly we’re lacking some important details.

Sanofi was more forthright. Acomplia was pulled from shelves because Euro regulators thought the pill was too dangerous for sale; and the same authorities asked Sanofi to stop its ongoing trials for the same reason. Merck stopped its version because it had similar side effects seen in Sanofi’s — weird mood changes and depression.

Interestingly, all three drugs acted on cannabinoid receptors. So how likely is it that Merck and Sanofi’s drugs were riddled with side effects while Pfizer’s was just fine? Hmmm.

None of this news is surprising to BNET readers. Back in July we noted that “Drug companies have been down this route many times before, and always failed to find success. A safe and effective weight-loss pill is like Big Pharma’s El Dorado — a lost city of gold that no one can find.”

It’s worth repeating the explanation for why these pills tend to fail, provided by Derek Lowe of In the Pipeline:

Evolutionary pressures have been too strong — our metabolisms try to make absolutely sure that we have plenty of reserves against the lean times, because over most of the history of our species, it’s been nothing but lean times….

So many of the weight loss drug attempts have been in the area of appetite suppression — stop the problem before it develops. But you run into those multiple pathways there, too — any animals whose feeding behaviors can be easily shut down are long dead. We’re the descendants of the opposite population: the ones that scrambled for food no matter what.

Posted in diet, drugs, obesity | Tagged: , , , , , | Leave a Comment »

Drug Marketing by Acronym. ACCORD and the Power of Myth

Posted by Colin Rose on July 14, 2008

CHRISTMAS, COURAGE, DIAMOND, DREAM, ILLUMINATE, ILLUSTRATE, REACH, PARAGON, PRAISE, PREVENT, ONTARGET, PROVE IT, ENHANCE, ACT, BEST, ADVANCE, HOPE, LIFE, PROSPER, CALIPSO, ASTEROID, ACCORD, CASHMERE, MIRACL, SYMPHONY, all names of recent drug studies that are carefully constructed pseudo acronyms invented by highly-paid marketers, implying that the drug studied has wonderful properties to prolong your life make it much more pleasant and worry-free. The marketers have learned that the name of the trial is more important than the results of the trial. Who would be attracted to older trials named WOSCOPS or LRC-CPPT? Would it really matter what the results of DREAM were? The acronyms imply that regardless of the result of the study the drug must be good for something. If one fiddles the statistics one can always find a sub-group in which the drug had some effect. You will never see a drug trials with the acronyms, DISEASE or DEATH but many of them do result in more of either of both.

To take one example, just the association of a drug with a trial like ACCORD (Action to COntrol Cardiovascular Risk in Diabetes) will give it cachet. But the results of the drug “action” in ACCORD was that  adding more expensive drugs to the usual cocktail to markedly lower blood glucose to an arbitrary “target” in type 2 diabetics with known vascular disease caused more deaths than not meeting the “target”. The latest expensive drugs for DM2 were supplied by the usual suspects: Abbot Laboratories, Amylin, AstraZeneca, Bayer Healthcare, GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Sanofi-Avenis, Schering-Plough. Seven of the lead authors have received drug money from multiple companies. But will the results of this study made a dent in the sales of the latest heavily-marketed, expensive drugs like Diamicron, Prandase (Precose), Amaryl, Avandia (Actos), and Byetta? Not likely. As an apologist for the drug industry who receives money from Amylin and Merck, stated in an editorial in the New England Journal of Medicine, this study “…[does] not provide a definitive answer to the problem of glycemic control and cardiovascular disease. Other ongoing clinical trials will provide additional clarification.” More dead people when taking more drugs is not clear? One of the studies we are to await is, wait for it, ORIGIN. Reminds one of the Garden of Eden. So, the myth of the necessity to “normalize” symptoms or metabolic self-abuse that might even be protective will persist and these unproven drugs will continue to be prescribed for many more years costing the medical systems of the world many $billions and making huge profits for their makers, in spite of the total absence of proof that anyone is better off or living longer swallowing these drugs.

Legal Addictions

The ACCORD-type subject

These drugs were approved for sale purely on basis of their ability to lower blood glucose, a symptom of a self-abusive, atherogenic lifestyle. Look at the baseline characteristics of participants in ACCORD. Average BMI was 32. Obese is defined as BMI greater than 30. So almost all participants were obese. Is it not unethical to perform a drug study in such a group before they have all reduced their BMIs to under 25? Normalizing their weights, by far the most important “action”, would probably cure the diabetes in many of them and they wouldn’t even be in a study on diabetes. But one cannot sell drugs to healthy people. So why would any investigator receiving money from drug dealers insist that people with self-abusive lifestyles change their lifestyles before doing a drug trial? After all, no investigator wants to risk dying of old age before he or she can collect enough “events” (i.e. deaths) to write a paper whatever the conclusion might be.

Results from ACCORD. More deaths on “intensive” (more expensive drugs) therapy

Drs Krumholz and Lee, both with no ties to drug dealers write in a Perspective article in the same issue of the NEJM. “Clearly the way in which risk factors [blood cholesterol, blood glucose, high blood pressure] are modified does matter. Lifestyle interventions may [sic] have few risks, but we cannot assume the same for drugs…”  “…ultimately we need to understand a strategy’s effects on people, not just on surrogate end points.” But even they refuse to recognize the absolute need for lifestyle change before starting drugs in patients with diseases of lifestyle. What risks could lifestyle change possibly have?

Posted in atherosclerosis, coronary artery disease, diabetes, Type 2, diet, drugs, obesity, professionalism | Tagged: , , , , , , , , , , , , , , , , , , , , , , , , , | Leave a Comment »

REACH, “atherothrombosis”, and the marketing of Plavix

Posted by Colin Rose on June 23, 2007

An example of a “free” paper in a prominent medical journal reporting a study funded by industry.

Let’s examine what is behind this beneficence.

Disney World

The REACH type subject

REACH is an an acronym for REduction of Atherothrombosis for Continued Health. The term “atherothrombosis” was concocted by “industry” to market Plavix and has now infiltrated into the literature. This is a classic example of marketers inventing a disease for which their drug is the cure. The first and most lucrative was the invention of the disease,”dyslipidemia”, to market statins.

The web site, http://www.atherothrombosis.org, is funded by sanofi-aventis and Bristol-Myers Squibb who sell Plavix. Dr. Bhatt, an author of REACH, is prominent on the site. Here is a quote from the site by a Dr. Cannon:
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Atherothrombosis vs atherosclerosis: Different diseases?

The patients were divided into those who had had a prior event versus those who had not. Interestingly, the patients who’d had a prior event each had about a 20% reduction in death, MI, stroke over the subsequent 2 ½ years in this otherwise pretty stable outpatient population. On the other hand, there was no benefit whatsoever in those who had coronary disease without a prior MI, or cerebrovasculardisease without prior stroke. So, in thinking about this, the question comes up: ‘Does this mean that the patients with a prior event are different?’ They’ve had a thrombotic event as part of their course of vascular disease. The question popped into my head: ‘Would this mean, potentially, that atherothrombosis might be a different disease than atherosclerosis?’

If we circle back to thinking clinically, there are a lot of patients we see who are 80 years old who finally come in with evidence of angina and have diffuse atherosclerotic disease, but who have never had an MI or stroke; then there are other patients who come in at age 40 with a large anterior MI and just one atherosclerotic lesion on their cath. Those would seem to be two extremes: the atherosclerotic patient (the 80-year-old with diffuse disease) and the atherothrombotic patient (the person who comes in with an acute event). And, the difference in the benefit of dual antiplatelet therapy for the atherothrombotic patient makes perfect sense: you’re treating a thrombotic disease with an antithrombotic agent. This may give us insight into subcategorizing a little bit the disease process itself and targeting long-term therapies.
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Readers should be made aware of the disclosure of Dr. McDermott, the editorialist:
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Financial Disclosures: Dr McDermott reports that she has received honoraria from Bristol-Myers Squibb, Sanofi-Aventis, NicOx, and Otsuka Pharmaceutical, has served as a consultant for Hutchinson Technology, and is currently receiving support from research grants from the National Heart, Lung, and Blood Institute.
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Why couldn’t JAMA find an editorialist with no connection to “industry”, particularly the company funding the study which was editorialized?

If you wonder why this is a “free” publication just look at the disclosures and funding:
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Financial Disclosures: Dr Bhatt reports that he has received honoraria for consulting on scientific advisory boards from AstraZeneca, Bristol-Myers Squibb, Centocor, Eisai, Eli Lilly, GlaxoSmithKline, Millennium, Otsuka, Paringenix, PDL, Sanofi-Aventis, Schering Plough, The Medicines Company; honoraria for lectures from Bristol-Myers Squibb, Sanofi-Aventis, and The Medicines Company; and provided expert testimony regarding clopidogrel (the compensation was donated to a nonprofit organization). Dr Röther reports that he has received honoraria from Bristol-Myers Squibb and Sanofi-Aventis. Dr Steg reports that he has received honoraria from Bristol-Myers Squibb and Sanofi-Aventis and has received research grants from Sanofi-Aventis. Dr Steg reports having served as a member of the speakers’ bureau for Boehringer Ingelheim, Servier, GlaxoSmithKline, Merck, Sharp & Dohme, and Nycomed and also on a consultant ad board for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Sharp & Dohme, Sanofi-Aventis, Servier, and Takeda. Dr Ohman reports that he has received research grants from Berlex, Sanofi-Aventis, Schering-Plough, Eli Lilly, Bristol-Myers Squibb, and Millennium. Dr Ohman reports that he has stock ownership in Medtronic, Savacor, and Response Biomedical and is a consultant for Invoise, Response Biomedical, Savacor, and Liposcience. Dr Hirsch reports that he has received research grants from Bristol-Myers Squibb and Sanofi-Aventis; honoraria from Sanofi-Aventis; and speaker’s bureau fees for Sanofi-Aventis. Dr Wilson reports that he has received a grant from Sanofi-Aventis. None of the other authors reported disclosures.

Funding/Support: The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan), who assisted with the design and conduct of the study and data collection.
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Call me paranoid but I have a suspicion that the conclusion of the next paper from REACH will be that “dual anti-platelet” therapy (read ASA and Plavix) is underused. Thus the “reduction” in REACH.

But the sponsors may have shot themselves in their feet. The REACH data shows that in Japan the use of statins is about two-thirds and hypertensives one-half of the world average but Japanese all-cause mortality is 40% less than the world average. Also the Japanese used about the same “dual anti-platelet therapy” as the world average. So, total mortality has no relation to drug use of all types. This glaring paradox is nowhere mentioned in the paper or the editorial and I doubt most readers will look at the data themselves.

In the final analysis, what is the point in studying atherosclerosis in a population in which 80% are overweight or obese, 44% are diabetic, 82% are hypertensive and 16% are smoking? The causes of their atherosclerosis are obvious, food and/or tobacco addictions as we have known for many years.

If sanofi-aventis and Bristol-Myers Squibb really want to reduce “atherothrombosis” and improve health they should fund programs for fighting these addictions instead of doing more surveys to try to justify more drug sales. From their own data it is clear that drugs do not increase life expectancy.

Posted in atherosclerosis, coronary artery disease, diet, professionalism, Uncategorized | Tagged: , , , , , , , , , , , , , , , , , , | Leave a Comment »

Get With The Guidelines – Do as the drug salesmen say

Posted by Colin Rose on May 4, 2007

Here is a classic example of drug dealers influencing the prescribing habits of doctors. If you read this GWTG-CAD carefully you will find a litany of insinuations WITHOUT PROOF. The data presented here are only observational. There is no control group. What were the lipids of the population that didn’t have a heart attack? The main insinuation is that the only cause of atherosclerosis is “dyslipidemia” and if the whole population of the world achieved “ideal” lipid levels by taking enough statins to lower their LDL to less than 70 mg/DL and somehow managed to also get their HDL higher than 60 mg/DL, there would be no heart attacks. There is NO PROOF for this hypothesis. 21% of the heart attack patients were on statins before their heart attack but still had one!

Now, if you want to know how such stupidity gets into print and gets the backing of the AHA, just look at the disclosures which are in small print at the bottom left. Enough said.

Posted in cholesterol, coronary artery disease, drugs, professionalism, statins | Tagged: , , , , , , , , , , , , , , , , , , , , , , , , , | Leave a Comment »

COURAGE demolishes the myth of the “widow maker” and the “time bomb” but does not use optimal medical therapy

Posted by Colin Rose on March 26, 2007

For 30 years since the development of a balloon-tipped catheter to dilate coronary arteries, now known as PCI (percutaneous coronary intervention), it has been revealed truth from “experts”, most of whom paid their mortgages by doing PCI’s, that all significant coronary narrowings should be dilated to prevent a heart attack. In spite of overwhelming evidence that heart attacks are caused by rupture or early, unstable, non-obstructive plaques, most cardiologists still believe that heart attacks (sudden complete blockage of a coronary artery) occur at the site of the largest plaques. Patients are shown angiograms and told they have a “widow maker” or are “sitting on a time bomb”. I refused to do angioplasties until there was some proof for this superficial but very lucrative theory. Again, it turns out I was right. Even in patients with major narrowings and symptoms, PCI does not prolong life or prevent heart attacks. Chronic symptoms were slightly more improved in the PCI group but most medically-treated patients had symptom improvement just with pills.

 

Legal Addictions

The COURAGE type subject

All cardiologists give lip service to the necessity for lifestyle change as the ultimate cure for atherosclerosis, but in this study there was no attempt at lifestyle change. Most patients were overweight or obese, gained weight over the five year study. 20% smoked and did not stop. While the authors claim to using “optimal” medical therapy, they did not even try significantly changing lifestyle, the obvious cause of the patients’ atherosclerosis. No doubt even better results that could have been obtained with just lifestyle change, without pills or PCI, as Dean Ornish showed many years ago.

If you want an explanation for why, except for a feeble attempt to raise HDL by exercise, NO attempt was made to change lifestyle meaningfully before using statins or PCI you need look no further than the source of funding and the disclosure statements of the authors. Those who recieve substantial income from drug dealers are not keen on proving that cost-free lifestyle change alone will do the same or better than expensive drugs.

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Now, why has it taken 30 years to finally prove the futility of PCI in patients with stable or stabilized coronary disease? Unlike new drugs, there are no rules and no government agency mandating that surgical procedures have to undergo clinical trials before being done on the general population. Any surgeon can develop some operation that seems superfically rational and he and his colleagues can do many thousands of those operations, costing millions or billions of dollars and risking many lives until someone gets around to actually testing it to see if the outcome is really as advertised.

Doctors profess to want to practice “evidence-based medicine” but when change negatively affects bank accounts habits change very slowly if at all. Angioplasty in stable CAD can always be rationalized by the classic, “my patient is different than those in the controlled trial”. We can predict that angioplasties in patients with stable CAD will not decline significantly until most of those trained in the procedure have retired. The system could save a lot of money by giving each of them $one million and a house in Mexico to retire to.

Posted in angioplasty, atherosclerosis, coronary artery disease, diet, drugs, professionalism, statins | Tagged: , , , , , , , , , , , , , , , , , , , , , , , , , , , , | 1 Comment »

 
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