HDL Cholesterol May Not Help The Heart After All
9 CommentsBy Ed Silverman // June 3rd, 2008 // 7:08 pm
The good cholesterol that scientists have thought helped unclog arteries had no effect on heart disease in a study published today in the Journal of the American Medical Association, casting doubt on a theory drugmakers have spent more than $1 billion pursuing, Bloomberg News writes.
Researchers studied people who have a genetic condition that causes them to produce very low levels of HDL cholesterol, expecting they’d be about twice as likely to have heart disease. Instead, they had no greater risk, throwing into question the notion that raising HDL helps reduce plaque in arteries, a theory Pfizer, Merck and Roche have all pursued at various times, the wire notes.
“There is really no evidence that this method is going to work,” Anne Tybjaerg-Hansen, a study and clinical biochemistry researcher at Copenhagen University Hospital, tells Bloomberg. “This theory has been around for a long time, but this study just doesn’t support it.” The reason may be that other HDL research examined patients with high levels of triglycerides, not low HDL levels, may have caused their increased heart risk, she adds. Here is the abstract.
This may explain why torcetrapib, which Pfizer spent more than $1 billion developing, raised HDL levels without providing heart benefits, according to the study. Analysts had expected torcetrapib would have more than $14 billion in annual sales, but Pfizer halted development in 2006 due to increased deaths. Meanwhile, Merck and Roche continue to develop drugs that raise HDL.
Yale Mitchel, Merck’s vp of cardiovascular disease research, says the study, which was small and in a rare patient population, won’t persuade the drugmaker to change its plans, given the large body of data suggesting HDL provides a benefit. Merck has spent five years developing a drug called anacetrapib, which raises HDL by blocking the cholesterol ester transfer protein, Bloomberg writes, adding that the drug is in the third and final stage of testing necessary to gain regulatory approval.
“The hypothesis on whether CETP inhibition is a benefit or not hasn’t been tested and it is too attractive a mechanism to disregard right now,” Mitchel tells Bloomberg. “We have to be careful about not over interpreting it at this point. There is a large contextual database that suggests low HDL levels are associated with an increased risk.”
Pfizer’s HDL research is temporarily on hold, while Roche’s drug is in the final stages of testing and it will file for FDA approval after 2011. “We haven’t had an opportunity to evaluate this study yet, but epidemiological data does show there is a strong inverse relationship between HDL and cardiovascular risk,” a Roche spokesman tells Bloomberg.
The idea that HDL helps purge artery plaque is based mostly on animal studies, which Tybjaerg-Hansen said are sometimes difficult to understand and apply to humans. The study looked at data collected from almost 57,000 Danish patients between 1976 and 2007, of which 148 had a rare genetic condition called Tangier disease that caused them to produce very low levels of HDL cholesterol.
Nathan
More than $1 billion spent pursuing something that may not even produce a viable drug… That should give everyone a clue why drugs are so expensive.
Laurie
One billion dollars spent on a drug to treat something that “may” not be a pathological problem. Common sense would tell one to confirm the negative effect of a condition before making a drug to treat it.
CMC guy
Laurie this is just the scientific method in the real world IMO. Everything starts as an idea then assumptions/connections get built and tested with often limited real solid/complete evidence and correlations so always on the edge of unknown. Don’t know full story yet does seems could have been questioned sooner. Here it seems that had animal models where translation to humans not holding up which is regular part of pharma (cancer cures in mice). Common sense may suggest most scientists should have gone to business or law school rather than pursue careers of continual frustration and infrequent successes that most endure.
Marilyn Mann
Aren’t there studies of the effect of HDL levels that control for trigs and remnant lipoproteins? Anyway, the questions of whether low HDL due to a particular type of mutation is linked to heart disease, and whether a drug that raises HDL by some other mechanism prevents heart disease seem like quite separate issues.
Lipid Doc
I think that this is an extrapolation that goes too far. Just because low HDL-C levels in this population do not confer increased risk for CVD eveents, doesn’t mean that low HDL-C in patients with high LDL-C and TG or high CV risk will not be of benefit. Either way, we need evidence to decide. Epidemiologic results sometimes yield strange results.
Condor
Ding! Marilyn Mann hit that nail on the head.
It may be a three-or four step (or more) chain — low HDL, tied to ?, tied to mutations(?), tied to increased risks, tied(?) to the MECHANISM used to raise HDL levels — as opposed to any simple one-for-one cause and effect.
And Nathan — this level of spending (north of $1 billion!) probably tells us more about the relative competencies of management at some drug companies — than it does, about what such drugs really cost. [Or SHOULD cost.]
Nathan
Condor,
Cardiovascular disease is the #1 killer in the US and accounts for 30% of ALL deaths in the US every year. Is that $1 billion in research really due to incompetent management? We spend about $40-$50 billion EVERY YEAR in pharma research. This $1 billion was a drop in the bucket.
In spite of what many of you think, big pharma money won’t buy anything at the FDA - only good science will get a drug approved.
Condor
Hi Nathan — I guess I missed the part of anyone’s post where it was insinuated that the FDA can be “bought” — I know just the opposite to be true. Odd, though, that you’d phrase it in that way, when no one suggested it.
Now, actually — over 41,000 people die in car crashes in America each year, far outstripping death by CVD — that, in fact, is the No. 1 preventible cause of death in America, Nathan. See the Federal Department of Transportation report:
http://hazmat.dot.gov/riskmgmt/riskcompare.htm
But of direct concern to pharma, here, according to the CDC’s 2006 report, of the 220,267,000 Americans over the age of 18, 15,820,000 had one or more forms of cancer, while a slightly larger number, or 24,107,000 had some form of heart disease. See this PDF:
http://www.cdc.gov/nchs/data/series/sr_10/sr10_235.pdf
So, if I were to accept your figures as generally accurate — $40 to $50 billion spent, annually, in pharma research — I guess I’d ask why are we spending ONLY $1 billion on R & D in the field of heart disease?
How much is spent in R & D in the field of cancer?
Where is the other 98 percent going? [And I KNOW it doesn't go to payola for FDA or EU authoriites, to be silly, but also abundantly clear.]
So, I guess I do see a fair basis to question competencies of pharma management — IF your R & D figures are accurate.
Nathan
Condor,
$1 Billion was spent on a single CV mechanism of actions. Far, far more than that is being spent on the entire field of CV research. If I had to take a stab at it based on my company’s expenditures, I would say that about 15% of research budgets are spent on CV research. At my company, about 20-25% is spent on cancer research.
I realize that in this comment thread no one has suggested we can buy off the FDA. It has, however, been suggested many times that big pharma can simply get nearly anything approved given enough money. The failure of this $1 billion to generate a single drug (so far) clearly illustrates that cold, hard science is really behind drug approval — not behind the scenes payoffs. That was my point. (I realize you weren’t suggesting this, but I know full-well many commenters on this site believe that to be true)