Researchers theorize that medically elevated HDL may not be as effective as natural HDL at whisking away bad cholesterol.
Novartis is testing a drinkable form of HDL (invented by UCLA's Fogelman) that doesn't aim to raise HDL levels.
This causes dramatic boosts in HDL. Torcetrapib boosts levels of HDL by 70%, and Merck's drug boosts HDL by 130%.
But he concedes that there are good HDL particles and bad HDL particles, and the bad ones might increase artery inflammation.
In 19 patients with low levels of HDL (high-density lipoprotein), the Pfizer combo raised HDL counts by 61%, with few side effects.
Although clinical trials of HDL-boosting CETP inhibitors have so far failed to produce positive results, many other avenues of HDL-related research remain active.
FORBES: Early Look: New Methods To Enhance Cholesterol Efflux
This created an environment where researchers talked about HDL levels as all-important, ignoring the fact that HDL was much more poorly understood than bad cholesterol.
They're trying to figure out whether the problems with torcetrapib come from lowering HDL cholesterol, lowering a particular type of HDL cholesterol, or from some unique characteristic of the torcetrapib molecule itself.
Researchers speculating about what went wrong thought perhaps torcetrapib made HDL that didn't work, or that HDL itself (short for high-density lipoprotein, and often called "good cholesterol") was less powerful than they thought.
Another potential beneficiary is Kos Pharmaceuticals, which makes a preparation of niacin to raise good cholesterol, or HDL. Patients on Crestor in this trial had a surprisingly big jump in HDL. The big question is how much doctors will embrace this single study.
In the study where it helped patients lose weight, the drug also raised good cholesterol, or high-density lipoprotein (HDL), by 23%, almost as much as Niaspan, the sustained-release niacin drug made by Kos Pharmaceuticals (nasdaq: KOSP - news - people ) that is the main currently available treatment for raising HDL. Rimonabont also cut triglycerides, another risk factor for heart disease, by 16%.
But Tall has gone back and forth over the years over whether raising HDL will work.
It's difficult to know, but there are signs an HDL-raising pill might be marketable.
In these people, the combination of torcetrapib and Lipitor raised HDL 57% more than Lipitor alone.
High-density lipoprotein, better known as HDL or "good cholesterol, " has become a medical mainstay.
Last November Pfizer announced the failure of torcetrapib, a drug to boost good cholesterol (HDL).
Merck unveiled another kind of HDL-raiser, a drug to inhibit the cholesterol ester transfer protein (CETP).
Indeed, research has long shown that people with high HDL levels face fewer heart attacks.
As expected, mipomersen also resulted in significant reductions in app B, total cholesterol, and non-HDL cholesterol.
The promise of niacin, which can raise HDL by as much as 26%, is long established.
Meanwhile, other firms are seeking to use modified versions of the HDL protein itself.
Pfizer, Novartis and others are working on synthetic HDL that can be injected or even swallowed.
Even if all those drugs fail, other methods of raising HDL might prove effective.
Some even argue that focusing on HDL exclusively may have been a scientific wrong turn.
But the relationship between HDL and heart disease turned out to be maddeningly complex.
The mysterious HDL is thought to unclog arteries gunked up by too many french fries.
Pfizer's torcetrapib drug may have produced large amounts of dysfunctional HDL and just worsened the problem.
Every one point rise in HDL decreased heart disease risk by 2%, the Framingham researchers concluded.
Complicating matters further, HDL contains a constantly shifting array of 50 or more associated proteins.
Apo A-1 is thought to be the key HDL component that removes cholesterol from cells.
FORBES: Early Look: New Methods To Enhance Cholesterol Efflux
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