Q & A on Merck's Newest Cardiovascular Drug

So why is Merck's (MRK) 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 (ABT) 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 functions 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 (SNY) 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 the drug 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 (BAY). 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 (PFE).

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 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...

Comments

[Michael Lofrano]

Though I understand the reasons why the FDA would remain silent on the reasons for the non approval letter, I am pressed to figure out Merck's reticence. If the felt the FDA's issues were manageable and Merck could comply, why then hasn't Merck let investors know that?

Same logic applies if the issues questioned by the FDA were a deal breaker for the drug? Shouldn't Merck let the public know the likely outcome and simply state the drug is not likely to be approved? Is there a good reason, one that makes sense, for Merck's silence?
Anyone know? Unless, of course, Merck's scientists don't know themselves if the issues are addressable.

[Lipid Clinic Nurse]

Niaspan is NOT slow release niacin. It's extended release which clears in about 10 hours, and is very safe for the liver. Slow release takes 24 hours to clear, and is metabolized down a pathway that is NOT safe for the liver. Big difference.