This quote below of Derek Lowe, is an analysis of what happened to Torcetrapib, the Pfizer wonder drug that was supposed to increase HDL and decrease arterial plaque. It did not work out that well when it was tested in combination with Lipitor, the statin drug that effectively reduces serum cholesterol whilst not increasing HDL levels significantly. (60% more deaths in the test group over the control)
Torcetrapib was withdrawn, sending shockwaves into the community of like-drug developers. However people should be reminded that not all statins worked out well either. Bayclor, a statin, was rolled out into general use and then appeared to have a problem with some deaths 60 associated with its usage. This "hard end" marker, of fatality, is hard to associate unreservedly with this kind of drug's usage, since these sort of drugs are often used on people whose health is extremely compromised in the first place.
The difficulty in assessing the reasons for certain perceived drug reactions in the general population is that they are never known finally. It would be nice if there were some way of knowing where a potentially beneficial drug to, say, 80% of the population can be safely used, and where it is dangerous to the other 20%, its effects can be seen early by some sort of *magic* test, and thus discontinued for just that minority group. In effect, all drugs have problems with some people, and just that sort of strategy is employed for most prescriptions. But where the only marker of problems is sudden death, it is hard to prescribe experimentally.
In the case of some drugs undergoing clinical trials, an early death of the run out happens, and prejudicial dismissal is often employed. The question raised here is to the fairness of that approach. In many cases we can say there is no point in continuing, as more tests may just reveal more problems.. we are the possibility of just beating a dead horse ... but still in any trial there are often more questions raised than answered.
The Torcetrapib Catastrophe
Posted by Derek Lowe
This is a complete clinical disaster: the world's largest drug company just ditched their potential biggest drug. And this comes two days after a press conference where they talked about how they were planning to submit it for approval within months. Development of torcetrapib, the cholesteryl-ester transfer protein inhibitor designed to raise HDL levels, has been halted. Last week, that sentence would have been the subject of nightmares at Pfizer, but now it's the top of the news. No alarm clock buzz will make it go away. If you're looking for an example of just how difficult drug development is, look no more.
The story broke on Saturday: the 15,000-patient trial that was underway (half on Lipitor, half on Lipitor plus torcetrapib) showed excess deaths in the combination group (82 versus 51). That figure's impossible to ignore or explain away, and now the problem will be to explain what caused it. There are other CETP inhibitors in development, such as JTT-705 (from Japan Tobacco and Roche) and one from Merck as well. Both these companies have just had a tremendous shock, since we don't know (yet) if the patient deaths were due to CETP inhibition itself, the combination of it with the HMG CoA reductase inhibition of the statin, an off-target effect of torcetrapib with the statin, or just an off-target effect of the drug on its own. I'm sure that intense reviews of all the clinical data are going on. Things just got much more complicated.
As for Pfizer, they now have a monstrous hole in their near-term pipeline. Looking back, they've had a terrible run the last couple of years, with a number of promising drugs dropping on them, but nothing compared to this. I don't think anyone's had one to compare with this, at least in terms of the expectations for a drug. I was just talking with some people from the company last week (along with many of my colleagues), looking into employment possibilities. After this, I think we may have to keep moving. I don't think that Pfizer's going to be in the mood for hiring.
Another article on the Pfizer drug.
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