April 30, 2008
Merck Effort to Enter Supplement Biz Suffers Setback
Niacin or Vitamin B, commonly available as an over-the-counter supplement, works fairly well to lower bad cholesterol and raise good cholesterol with one major problem -- it causes severe flushing in many people. Merck thought combining it with an anti-flushing prescription drug, laropiprant, would solve that problem, and open a new vein in the anti-cholesterol gold mine for the faltering drug giant. It hoped to generate $2 billion from the drug, called Cordaptive.
The FDA's "not approvable" letter for Cordaptive, issued Monday, struck a blow to those hopes. Merck didn't say what the FDA's concerns were with Cordaptive, but they may center on laropiprant, the long-term effects of which have not been studied. "We plan to meet with the FDA and to submit additional information to enable the agency to further evaluate the benefit/risk profile of (Cordaptive)," Peter Kim, who runs Merck's research labs, said in a press release.
In October 2006, Merck launched a clinical trial in patients with inherited high cholesterol to study Cordaptive's effect on plaque buildup in the arteries. But the company suspended the trial after the unimpressive results of the Vytorin trial (ENHANCE, which also measured plaque) were announced.
Now Merck is studying Cordaptive in a trial called THRIVE, which plans to measure actual outcomes. However, that trial has been criticized on the grounds that it compares Cordaptive to placebo, not niacin (both arms get a generic statin). So clinicians will not be able to know the long-term effects of laropiprant.
That may explain why the FDA questioned this drug. Laropiprant binds to a receptor that some animal studies suggest may have neuroprotective effects, raising the need to evaluate its safety. -- PM
Posted by gooznews at April 30, 2008 06:48 AMFor the THRIVE study, I think it makes sense to compare to a placebo since it will be difficult to maintain blinding given niacin's side effects. So one is stuck with breaking the blinding and getting a biased estimate of the treatment effect or getting an unbiased estimate of the combined treatment effect of niacin and laropripant.
Posted by: Martin at April 30, 2008 07:00 AMGreat post, here, PM!
Now, to Martin's point -- his obervation makes sense to me, if one assumes it worthwhile to pursue this strategem, in the first place.
I may be reading too much into PM's post here, but I think one of the under- [un-]stated premises, in her piece, is that this idea of bundling-up old meds, with newer ones, and not fully-understanding the drugs' interactions -- one, with another -- by running true safety trials (in animal models, for example) with the combo's-delivery mechanism and effects. . . .
Is -- well, unwise, from a policy perspective.
[But perhaps that overstates her point, slightly.]
However, if one questions the Merck STARTING point, here -- and remember, we are not dealing with GRAS (Generally Recognized Aa Safe) compounds, in FDA-speak, here -- then we wouldn't really reach the question of "How (else) to [re-]design THIS study?", because we'd be doing entirely different, more basic, studies right now.
But the pill-poppin' public -- and their purveyor/pimps, particularly -- simply cannot wait THAT long (or spend THAT much, on basic research), right?
Right. [Well, now, perhaps mine is too-strongly stated, immediately above, but I doubt that anyone will miss the point of it.] Heh!
Again, cogent insights, here, PM!
With Gratitude,
-- the condor
Thanks for the comments. With respect to Martin's comment, my understanding is that laropiprant reduces flushing but does not eliminate it, so it would seem that some people will be aware that they are getting Cordaptive instead of placebo.
I agree with the condor that bundling an old drug with a new drug with an unknown safety profile does not seem like good public policy.
PM
Posted by: PM at April 30, 2008 05:06 PM There is an alternative to regular niacin that has been around for decades.......inositol hexanicotinate (non-flush niacin) and has a great deal of research behind it and a perfect track record of safety. Of course it's not a "drug."
That Merck would stoop to combining a B vitamin with an unsafe drug to make a "new" more worthless, unsafe cholesterol lowering drug indicates the depth of their depravity. The cholesterol-causes-heart disease theory has been throughly disproven.........how long before dumbed-down doctors and the American public awakens to this fiasco??
Statins have minimal effect on mortality rates in men only with CAD under age 65.......a 0.8%/year lower death rate over a 5 year period. That puny risk reduction is cause by a lowering of inflamation (nuclear Kappa beta), not cholesterol.
Therefore 96% of men who take them have no benefit and unknown long-term risks from Co Q 10 depletion (congestive heart failure and cancer risks), cholesterol depletion (neurologic diseases , cognitive dysfunction) as well as other unknown long-term risks.
The "benefits" clearly do not outweigh the risks. Heck, 15% of the patients I see cannot even tolerate statins for a short period of time due to muscle and joint aches alone. Statins have now also been shown to cause permanent mitochondrial damage in the muscle cell.
Randy Ice P.T., C.C.S.
Posted by: Randy Ice P.T. ,C.C.S. at May 3, 2008 12:30 PMBravo to Randy Ice! While the rest of the discussion is thoughtful and generally sophisticated, it ignores the most fundamental point, which is that the cholesterol HYPOTHESIS is at best unproven (and in fact almost certainly wrong). How can we ethically tolerate ANY study about "how best" to give a "treatment" (niacin) for which there is NO evidence of benefit -- when such study subjects its participants to substantial risk of harm?
Randy's other points about the marginal benefit of statins -- which is almost certainly unrelated to cholesterol modulation, as he notes -- are also powerful and important. But the issues around this attempt to add yet one more (old and cheap, but useless) drug to the hugely bloated patent-drug "cholesterol" market, by combining it with an expensive new "drug" whose only purported value is making the other one less noxious ... is stunning in its cynicism.
Posted by: Jerome Hoffman at May 3, 2008 01:07 PM