So why is Merck's stock dropping - again?
The FDA just unexpectedly handed them a "not approvable" letter for their latest drug, Cordaptive. Actually, we should stop calling it that, since they also told the company that they're not going to approve that name, either. What Merck's going to do with all their promotional freebies now, I can't imagine.
What's Cordaptive, or whatever it's called, anyway?
That's Merck's newest cardiovascular drug - although the active ingredient isn't new. It's niacin, also known as vitamin B3. It's been known for many years that niacin can both lower LDL cholesterol and raise HDL, as well as lowering triglycerides - in fact, it's probably one of the only things that can do all of those significantly at the same time.
So this is a rip-off, then? Merck's trying to sell vitamin B for $20 a pill?
No, it actually isn't, at least not to the extent you're thinking. The problem with niacin as a cholesterol therapy is that you have to take whopping amounts of it to see an effect. And there's a side effect - flushing of the face, which is basically uncontrollable blushing that can last for hours in some cases. That may not sound like much, but the great majority of people who take niacin at these levels have a problem with it, and a lot of people discontinue the therapy rather than put up with it. If the drug is taken for a few weeks, the flushing reportedly eases off some, but not everyone makes it to that point. By all reports, it's very irritating - and since patients can't feel their cholesterol being high, but can feel their faces burning and turning red, they solve the problem by not taking the niacin.
So why doesn't Cordaptive do the same thing?
A lot of people have tried to find a way to keep the lipid effects of niacin and get rid of the flushing. Merck added a prostaglandin receptor antagonist, laropiprant, to try to block the pathway that leads to the vascular effects. And it seems to help quite a bit, which made the combination a potential winner. Abbott already has Niaspan, a slow-release version of niacin, which also has reduced flushing problems and does about $600 million of sales a year. Niacin therapy itself seems to be pretty safe, although you do want to make sure that liver and kidney function are normal before you start, so the only big question has been what blocking that DP1 receptor might do on the side: can you take that pathway out without causing more trouble?
Well, can you?
Apparently not. Actually, that should be "apparently there isn't enough evidence to say yet" - that's probably more in the spirit of the FDA's letter. They want to see more information about the drug. Problem is, the FDA treats this (properly) as a matter between the agency and the drug company, so they aren't saying what the problem is. And Merck, for its part, isn't saying, either. Investors feel rather left out in these situations - perhaps the most striking one in recent years was Sanofi-Aventis's absolute wall of silence for months about why the FDA wasn't approving their potential blockbuster Acomplia (rimonabant).
Why's this so unexpected, if there wasn't enough evidence given to the FDA?
Well, there seems to have been enough evidence in the same pile of data for the European Union, whose regulators approved recommended the drug for approval a few days ago. Merck must have felt reasonably confident that they'd get the same treatment here. No such luck. And as just mentioned, we don't know if the problem is not enough evidence of efficacy, not enough evidence of safety, or a bit of each.
Why don't you people just make cholesterol-lowering drugs that work better, then, so there's no doubt about efficacy?
Would that we could. Statins basically only lower LDL - they don't raise your HDL. And if you push the statins too hard, patients start coming down with rhabdomyolysis, and you don't want that - ask Bayer. Raising HDL has proven to be a real challenge, too. There are a lot of ideas about how to do it, but the most obvious ones aren't working out too well - ask Pfizer.
OK, then, why don't you just make safer versions of what you already have?
Would that we could. But in almost every case, we have no idea of how to do that. For the most part, either the safety concerns are tied up with the beneficial mechanism of the drug, or they're occurring through side pathways that we don't understand well and don't know how to avoid. And some of those are things that you don't even get a read on until your drug gets out into the market, which is no way to do things, either.
So, why is the drug business considered such a safe bet?
Now, that one I don't have an answer for. Unless it's the conviction that people are always going to get sick, which I guess is a pretty safe bet. And that's coupled with a conviction, apparently, that we're always going to be able to do something profitable about that. And some days, I have to wonder. . .
1. LNT on April 29, 2008 10:28 AM writes...
I'm not sure that very many people few the pharmaceutical buisness as a "safe bet" anymore. That used to be the investment advice of the past: invenst in utilities and pharmaceuticals in times of economic uncertanty. But I sure haven't seen evidence that pharmaceuticals have fared any better than the general market in this latest economic downturn.
Permalink to Comment2. The Pharmacoepidemiologist on April 29, 2008 10:54 AM writes...
There were some problems not mentioned--like elevated liver enzymes--that's a major no-no at FDA these days (ever since Rezulin and Exanta). Also, there were no mortality data submitted--ever since the decline of Pfizer's HDL-blockbuster-to-be with elevated mortality, it's a given FDA's going to want mortality outcomes data. Merck didn't provide that. Seems to me FDA's on the job, and Merck wasn't. Maybe someone at Merck needs to review their job description and get to work on getting the data needed to get drugs approved?
Permalink to Comment3. SRC on April 29, 2008 12:08 PM writes...
Why don't you people just make cholesterol-lowering drugs that work better, then, so there's no doubt about efficacy?
Am I the only person whose blood pressure rises (topical, yes?) on being asked silly, juvenile questions such as this?
I feel like slapping my forehead and saying, "My God, why didn't I think of that?" just to check the reaction.
Permalink to Comment4. milkshake on April 29, 2008 1:35 PM writes...
SRC: you are either very naive or you must be a stooge in pay of these evil corporations (who just want everybody to stay sick and die because if people knew about the amazing 100% natural cures and intestinal clensing and revitalising methods, everybody would stay healthy and the pharma companies would be out of business). Read some book from Kevin Trudeau and you will see the light.
Permalink to Comment5. SRC on April 29, 2008 1:44 PM writes...
Thanks for the tip, Milkshake. I am in fact both very naive and diabolically cunning, as we stooges in the pay of corporations (evil is understood) must be. It's a difficult balancing act. We stooges just hope "the people" don't find out about the magical cures effected by yam suppositories. Cheap, cures everything, no side effects. Shhh. Mum's the word. Pass it on.
Permalink to Comment6. arby on April 29, 2008 7:08 PM writes...
Yam suppositories, you say? A diabolically cunning stunt. rb
Permalink to Comment7. Derek Lowe on April 29, 2008 8:09 PM writes...
I must have a pretty broad sense of humor, because I enjoyed that one a lot. . .
Permalink to Comment8. milkshake on April 29, 2008 8:26 PM writes...
your enjoyment was 100% natural - yams are long-known to be good for the body
Permalink to Comment9. anon on April 30, 2008 6:13 AM writes...
Derek, you're mistaken that the drug was approved in the EU. It was recommended for approval by an advisory committee.
Permalink to Comment10. Jonadab the Unsightly One on April 30, 2008 7:24 AM writes...
Yam suppositories are only really effective if used in combination with the proper diet and exercise regimen. Research regarding the ideal diet for this is still ongoing, but early indicators point to yellow raisins and habanero peppers every morning for breakfast. For information about the exercise regimen, send $49.99 to me...
Permalink to Comment11. burt on April 30, 2008 7:45 AM writes...
"Yam suppositories" um--How long does it take the yam to dissolve? I guess you'd want one of those long, skinny ones?
Permalink to Comment12. Milton on April 30, 2008 4:46 PM writes...
You're making fun of Kevin Trudeau ? Have you naive scientists ever talked with a drug rep or witnessed their hard-ball tactics? Like finding out how many times a physician prescribes a particular drug then withdrawing free samples if they didnt prescribe the 'quota' amount? Or paying physicians to give bogus seminars?
Jeeze, you guys really lose your objectivity when it comes to the Drug lords.
Merck's other antics have already been commented upon by Derek.
I'll take yams to poorly studied pseudo poisons anyday.
Permalink to Comment13. ChemSpiderMan on May 1, 2008 11:41 AM writes...
Re. the approval letter in Europe. The combination is supposed to be called "Tredaptive".
From Wikipedia: On April 24, 2008, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of the combination, to be marketed in Europe as Tredaptive.
The structure of Laropiprant is on ChemSpider here: http://www.chemspider.com/Chemical-Structure.8043333.html
Permalink to Comment14. Sili on May 1, 2008 11:45 AM writes...
I fail to see how the less than fortunate methods of salespeople has any bearing on the efficacy of yams.
And call me silly, but I'd rather have a nice, shiny, newfangled, clean 'suppository' up my derriere.
Permalink to Comment15. SRC on May 1, 2008 12:46 PM writes...
You left out "diabolically cunning." That's very important.
Congratulations, my friend, on seeing through the drug company/FDA conspiracy.
And as luck would have it, I just happen to have a special on yams today, $49.95 for a bushel of yams organically-grown on mountainsides in Peru, where everyone knows the very best medicinal yams come from.
Order now and I'll throw in a year's subscription to my newsletter "Yam Recipes THEY don't want you to know about (and you probably don't want to know about either)," a $29.95 value.
Hurry! Order now!
Permalink to Comment16. JohnKRPH on May 5, 2008 10:49 AM writes...
http://www.endocrinetoday.com/view.aspx?rid=27231
http://endocrinetoday.com/view.aspx?rid=26549
If you think yams are any more natural than horses there is misperception in the air. Try reading these articles. Estrogens are estrogen. Estradiol in Estrace is estradiol in Biest or Triest.
Permalink to Comment17. James on May 8, 2008 8:51 AM writes...
Vitamin B, yams, et cetera aren't the only 'natural' items that help with cholesterol. There's a number of vitamins and supplements, many that should be part of a normal diet, that can enhance or supplant a drug like Cordaptive. See the reference list over at the Dietary Supplement Information Bureau.
Permalink to Commenthttp://www.dsib.org/cholesterol
18. Nancy on May 10, 2008 11:22 PM writes...
How high a dose of niacin is in Cordaptive? And, why couldn't a person use flush free niacin such as is available at Walmart?
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