Saturday, July 13, 2013

The Latest Breakthrough Cholesterol Drugs--More Deja Vu?

Gina Kolata wrote in the New York Times:
--about the search for a new drug that has the pharmaceutical industry all pumped up, and that indeed represents an exciting tale of medical progress.

I already don’t like the way this post is going to sound, so I’ll start backpedalling right off. I don’t want to sound like I am hoping that a promising new drug possibility ends up going bust. I don’t want to sound like I am hoping that people at risk for serious heart disease, who might be aided by this new drug, won’t be helped. But…

The exciting part of this story is that the promise of new therapies from mapping the human genome has thus far not produced anything like what it was hyped, but proponents have all along been saying, “Just wait.” And it does seem like this story depends on recent discoveries that allow a large number of people’s genomes to be put on the web and searched quickly with sophisticated software. Scientists became aware of a rare gene mutation that causes a very low level of LDL (bad) cholesterol. We know the higher your LDL, the greater your risk of having a heart attack or stroke, and vice versa.

Three drug companies, Amgen, Pfizer, and Sanofi, have been able to develop new drugs that appear to mimic the effects of this gene mutation. People taking the drugs in early tests have seen plummeting levels of LDL to points nearly undetectable—leading to concerns that some harm might even be caused as no physician sees such low levels in actual practice. The new drugs are not chemical but biological agents, monoclonal antibodies that have to be manufactured in living cells. The companies are betting on their success and developing new factory facilities that can produce unprecedented quantities of monoclonal antibodies.

So what could possibly be wrong with this picture?

Kolata fingers one fairly obvious concern. In today’s drug market, monoclonal antibody-type drugs are hugely expensive—such as some anticancer drugs. So are we talking about a new class of designer drugs that only the Warren Buffets of the world will be able to afford? Presumably the drug companies are trying to answer that concern precisely by touting the huge quantities of drug their new facilities are planned to produce. If on the other hand they marketed any such drug at a truly affordable price—instead of trying to milk the market for every last buck they could squeeze—it would really be a first.

If you read far enough into the article, another concern arises. Kolata does not mention this case specifically, but has everyone already forgotten ezetimibe?

Readers of this blog have not forgotten, of course, because y’all recall posts like this:

Ezetimibe was the drug contained in the brand-name products Zetia and Vytorin, and was highly touted in its day because it had a new mechanism of action. While one way to avoid heart disease is to have a low LDL, the other is to have a high HDL (“good cholesterol”), which is basically the same thing as all the cholesterol in your body is pretty much divided up into the LDL and HDL fractions. Ezetimibe was the wonder drug of its day because it seemed uniquely able to raise patients’ HDL, and in clinical trials, it did so quite successfully.

Only it did nothing at all to prevent heart disease and stroke.

So the lesson from everything we know so far about ezetimibe is that just because a new drug has an effect on various body measurements that mimic stuff which, when it happens naturally, is associated with lower risk of heart disease, doesn’t mean that the drug automatically prevents heart disease. You have to do longer-range trials to look and see whether it actually has such an effect. In the case of ezetimibe, I suggested in this other post:
--that the real take-home message might better be to have doubts about the whole theory that lowering cholesterol prevents heart disease—that statin drugs, for example, if they work to reduce the risk of a second heart attack after you’ve had a first (as they seem to), might well do so by reducing inflammation or something else, not by lowering cholesterol.

So maybe when they test out these new monoclonal-antibody drugs, they will be shown to really reduce the risk of heart attack, stroke, and death, and not merely to make one’s lab numbers look pretty. And maybe then the new drugs will also prove to be safe and not have nasty side effects. And maybe also the companies will actually manufacture them at a reasonable cost so that regular folks can afford them.

Maybe. But you can see why some would not be willing to put money on it.

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