Sunday, December 03, 2006

Pfizer's torcetrapib: Who Knew What, When?

Reported today in the Wall Street Journal:
"Pfizer Inc. halted development of a drug to boost good cholesterol that was the most important medicine in its pipeline, after more patients than expected died during a large clinical test. Half the people in the study, which was supposed to last three more years, took a combination of torcetrapib and Lipitor. The other half took only Lipitor. The company said that 82 patients taking a combination of torcetrapib and Lipitor died, compared with only 51 deaths among those taking Lipitor alone. Pfizer said the study cast no doubt on the safety and effectiveness of Lipitor." (see "Deaths Halt Development Of Pfizer Cholesterol Drug").
The unanticipated deaths became known Saturday after a board of independent experts reviewed the latest data from the 800 million dollar study, according to the report.

Who Should Know What, When?
I think this story is ripe for conspiracy analysis concerning who knew what, when. But it is also a story about what the public should know about drug risks and when. Here's my take on this.


Back in mid-October, Pfizer Chief Executive Jeffrey Kindler, at a Wall Street analyst meeting, softened Pfizer's message on torcetrapib's chances for early and resounding success. At that time, everyone was focused on the worry was over the discovery that torcetrapib raised systolic blood pressure an average of three to four millimeters of mercury (see "Pfizer's Top Experimental Drug Is Clouded by Blood-Pressure Rise").

Would a few millimeters prevent the risk-adverse FDA from approving the drug no matter what the benefits or did Mr. Kindler know something his medical consultants and chief medical officer did not know?

At the time, experts were divided as to how much they should worry over a few millimeters of mercury. The argument went straight to the issue of balancing risks vs. benefits. Defenders of the industry pooh-poohed the flap over the rise in blood pressure and suggested that the risk will be "far outweighed" by the benefit. This was the view of Alan Tall, a Columbia University professor and pioneer in research on good cholesterol who consults with Pfizer.
"We're still very positive about the drug," said Joseph Feczko, Pfizer's chief medical officer, in an interview. He acknowledged the blood-pressure increase but said scientists at the company still think the drug will have a positive "net impact" for patients by raising their good cholesterol and improving their clogged arteries. He said the company won't know for sure until completion of additional studies that will show, using ultrasound, the effect of the drug on arteries. (WSJ)
Death certain disrupted that plan to collect more evidence!

Pfizer should be commended for taking action, even it was a suspiciously-timed Saturday night massacre designed to attract as little media attention as possible on a weekend.

Role of AHA
One other side note involves the American Heart Association (AHA). The AHA prevented Pfizer from reporting on the latest clinical trial data at a meeting of heart specialists:

"Pfizer scientists were supposed to present the latest data on tests of an experimental drug to boost so-called 'good' cholesterol at a meeting of heart specialists in Chicago on Wednesday.

"Late last week the American Heart Association pulled the plug on that plan, ruling that Pfizer had violated the group's embargo by issuing a press release at the end of October that went into too much detail on the closely watched medicine, called torcetrapib.

"The upshot: Doctors and researchers did not get the chance to review data on the drug in detail and to question the Pfizer scientists responsible for them. Instead, Pfizer plans to make a presentation during the company's review of its research pipeline Nov. 30 in Groton, Conn., where the audience will be investors, not outside scientists and heart specialists. " (See "A Look Behind the Recent Flap Over a Pfizer Press Release")

AHA is obviously more concerned with upholding its "nondisclosure" policies than ensuring that important drug safety information reach key physicians. Fortunately for the US public -- but not so fortunately for some people in the study -- death occurred and further development of torcetrapib is a dead issue also. Otherwise, torcetrapib could have been another Vioxx!

The drug industry and physicians are always reminding patients that all drugs have risks and those risks have to be balanced against the benefits. Sounds good in theory, but if in practice the risks are not communicated early and widely, we do not have the information we need to make an informed decision.

For more discussion of acceptable risk, listen to the latest Pharma Marketing Talk podcast, which also covers legislation that may be in store for the pharmaceutical industry and new powers that may be granted to the FDA to increase the amount of risk information available to the public.


With regard to protecting the public from potential harm, I'd give Pfizer a B and AHA a D!

5 comments:

  1. I think the "informed decision" that you speak of should be made by experts--specifically FDA reviewers who are given all the information about a drug.

    The blood pressure data is important because blood pressure increases are correlated with mortality in high-risk populations. The fact that the Data Safety Monitoring (DSM) committee stopped the trial means that the expected risk was probably realized. The timing of the report is probably linked to the DSM meeting. DSM members typically have other jobs, so having a Friday meeting is not out of the question. It is not Pfizer who stopped the trial, but rather the DSM. That probably would not spin so well in the media...

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  2. A few mm of mercury.

    Remember, Big Pharma have sold antihypetensives on the basis that they significantly REDUCE risk when lowering BP by a few mm of mercury.

    So - why should the opposite not have been true.....that an increase of a few mm of mercury significantly raised the risk?

    What goes around....

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  3. Anonymous9:44 PM

    Torcetrapib was a good strategy for saving Lipitor. Too bad it increased all cause mortality (ACM). Pfizer would be wise to choose a statin enhancer that reduces ACM like that described at www.audaxinc.blogspot.com over two years ago.

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  4. Anonymous8:19 PM

    Everyone who fancies themselves as well informed: Pharma stock analysts, MD's, etc., might do well to Google the following:
    Bradley Bale Video
    Once there download & save or watch online the 26 minute clip.
    3880 CAD patients, 25% were secondary prevention [already had PTCA`s, CABG`s, MI`s, strokes] the remaining 75% were 2+ risk factors for CAD. Dr Bale nmanaged them "globally" for 10 years using an advanced lipid panel & CIMT scans and an innovative use of currently available pharmacotherapy:
    89% statins, 66% Niaspan. Treat the "bad' AND the "good".

    ONE MI & zero CV deaths in 10 years: A benchmark by any standard. HDL is the future & niacin has been proven for over 50 years to be safe & efficacious. Denying that the "flush" is managable is largely the observation of those who haven`t learned enough about the drug and never successfully kept >30% of their dyslipidemic patients on niacin beyond 3 months, as all of the following routinely do. Ask Dr Wm Castelli, Brad Bale, Varveris, Ziajka, et al.
    The future has "already been here" for quite some time,.. and now,.. there will be NO more available options [HDL] until 2010.
    All the rhetoric in the world can`t overcome the fact,.. Dr Bale is doing the "impossible",.. everyone else it seems, is denying that it can be done. Eventually everyone was forced to agree that the Sun did NOT revolve around the Earth,..rather the opposite was/is true. LDL will soon be eclipsed by the treatment of HDL. Increasing HDL2 by a mere 7 mg/dL, via niacin therapy, eclipses ANY benefit seen in any mono-therapy statin trial, but the real benefit is in COMBINING the 2 classes to reach event reductions in excess of 80%. Twice that seen in ANY statin-mono-therapy trial. This will be a proven concept within 5 years.
    CDP, CDP 15 year folow up, CDP NIDDM subnalysis, CLAS-I, CLAS-II, FATS, FATS follow-up, HATS, AFREGS, ARBITERS 1 & 2. All but the last 2 were NIH funded. Let`s watch closely the AIM-HIGH study [2010].
    SDMc

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  5. Statins and torcetrapib are both biochemical inhibitors that have not shown to save lives when compared with placebo unless you believe (regarding simvastatin only) in the sanctity of only 2 studies: 4S in men only and HPS in men only. The first study was run by Merck, the second one has not reported the mortality curves in their 4 groups, men, women, diabetic and not.

    The one study with statin in over 70 year olds, PROSPER, saved nobody but proved an increase in 'new' cancer with a study probability of 98%.

    Niacin is a mega-dose vitamin [B3] that has a heart attack benefit and a post study mortality benefit study to its name [Cor Drug Proj].

    My take on cholesterol is here http://www.health-heart.org/cholesterol.htm
    my take on the real cause of heart disease is here: http://www.health-heart.org/why.htm

    If it is a lack of micro-nutients [mainly B-vitaimins, omega-3 fatty acids and likely magnesium], drug approaches clearly cannot help much in primary prevention.
    vos@health-heart.org

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