Molecules: You'd better learn to live with them.
Pfizer's Lipitor is the highest-grossing drug out there right now. This single molecule sells over $10B/year. As discussed in the allopurinol entry, this is another example of a small molecule enzyme inhibitor. The class to which it belongs, the statins, works on one key step of the steroid biosynthesis cycle. They do a good job lowering LDL cholesterol, but aren't so great at raising HDL cholesterol.
That's one reason drug companies have been after a different class of anticholesterol drug. Another reason for Pfizer to be worried is that in just a few years, Lipitor goes off patent.
One protein responsible for processing HDL-C is called cholesteryl transfer protein (CETP). Lacking a functional CETP gene, one will exhibit elevated HDL-C levels. The idea here to design a small molecule that inhibits CETP, elevating HDL-C, thereby targeting another part of the cholesterol equation.
Torcetrapib is just such a molecule. It was getting close to making it to market. Just on Saturday, the plug was pulled because it was found that a group of patients taking both torcetrapib and Lipitor had a slightly elevated rate of death and heart problems versus a group just taking Lipitor - which is just the opposite effect you'd hope for.
Torcetrapib wasn't the only in-pipeline CETP inhibitor (in fact, Pfizer has others), but this is going to make everyone take a long, hard look at the class.
Comments
Yes, one financial ramification of torcetrapib in the toilet is the loss of potential sales for a company whose near-term pipeline is not exactly brimming over with new drugs. The other is that nearly 1 billion dollars have already been spent by Pfizer R&D on a compound that went south at a late stage. This highlights the risk of drug discovery & development. Derek Lowe has a good article on the news of what is a nightmarish scenario for a drug R&D organization.
Strictly speaking, CETP is not an enzyme but is more akin to a transport or carrier protein.
Posted by: Doc Bushwell | December 4, 2006 1:31 PM
OK, fixed.
Posted by: MoTD | December 4, 2006 2:16 PM
The dose is 120 mg twice daily. Sheeeit that's a lot of crap down the ol' pie hole! Uncle Al sees two chiral centers. Sepracor could save them.
"headache, asthenia, pain, dyspepsia, herpes simplex, herpes zoster, sweating, amnesia and abnormal thinking." "Abnormal thinking?"
http://www.jbc.org/cgi/content/full/280/15/14918
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Posted by: Uncle Al | December 4, 2006 2:30 PM
Yikes! That is one big, painful crash. But on the good side, I will get incorporated into my drug development lectures next year!
Posted by: Ian Musgrave | December 4, 2006 8:42 PM