| March
26, 2007--Eagerly
awaited results from a study of Pfizer’s now-abandoned
atherosclerosis therapy — torcetrapib — were released
this week, shedding some light on why the drug failed.
Torcetrapib
was once one of Pfizer’s brightest stars.
A bold new class of drug called a cholesteryl ester
transfer protein (CETP) inhibitor, this compound was a
prime contender for a lead spot in the lipid-regulation
market -- currently the biggest therapeutic class
worldwide, with sales of over $32 billion dollars.
But in a pivotal, $800-million trial, the drug
failed to slow progression of coronary atherosclerosis and
was linked to raised blood pressure.
Those
results sent a shockwave through Pfizer, which abandoned
the drug and promptly laid off 10,000 staffers. The
findings also raised worries about other CETP inhibitors
in development.
The
new report, published by the ILLUSTRATE trial group in
The New England Journal of Medicine this week, does not provide a thorough explanation for why the compound
failed to have its intended medical effect.
However, the study shows that the combination of
torcetrapib with Pfizer’s blockbuster
cholesterol-lowering drug, Lipitor (atorvastatin) was
having the intended effect:
Blood HDL levels (the good cholesterol) were going
up while LDL levels (the bad cholesterol) were going down.
This
trial used imaging tools — coronary intravascular
ultrasonography and carotid ultrasonography — to measure
physical effects in patients.
Writing in an editorial
that accompanied the study results, Alan R. Tall said the
imaging studies were “disappointing,” but it still
seems likely the compound’s side effects were
“…caused by nonmechanism-related toxicity
of this particular drug.”
Tall
also pointed out that there were no signs that the drug
worsened disease, and there appeared to be “…some
improvement in a secondary measure of plaque
volume.” Finally,
he wrote: “This finding suggests modest regression of
plaque and provides a glimmer of hope for the
future development of this class of drugs.”
For
more, see articles in Forbes,
The
Wall Street Journal, NEJM
editorial, and
NEJM
ILLUSTRATE study report. |
