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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline

« Now With the Great Taste of Fish! | Main | Memo to the Public Relations Department »

July 5, 2006

More Statin Skirmishing

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Posted by Derek

The word today is that AstraZeneca and Abbott are going to combine two of their cardiovascular therapies. Crestor, AZ's statin, and a new fibrate, the successor to Abbott's TriCor, will be sold as a single pill. Its name will, I feel sure, end in "-or". This is part of the next wave of cholesterol drugs (and drug mixtures), which are aiming to simultaneously lower LDL (via the statin) and raise HDL (the fibrate's contribution, in this case). A number of other "statin-plus-something-to-raise-HDL" projects are in the works (including a bet-hedging one from AstraZeneca with a totally different drug candidate from a small company called Atherogeneix).

As for these two components, Crestor is a powerful statin indeed, bordering perhaps on too powerful, and if it's possible to describe a billion-dollar drug has having disappointing sales, this is the one. (After all, if you listened to the analysts back before it was introduced, it was supposed to be selling three times that amount by now). And TriCor is a fibrate, one of a mechanistically baffling class of lipid-modifying drugs which have been in use for quite a while now. If you look through the literature, particularly in patent claims, you can see that the idea of combining statins and fibrates has been proposed many times before. It's a sensible combination, although (as with many of these ideas) it's something that you could probably also achieve by taking two separate medications. It would be interesting to know how many people are doing just that at present.

Another thing that would be worth knowing is how well this idea works with Abbott's next-generation fibrate compared to generic fenofibrate, and how well either one would work when combined with, say, generic simvastatin (Zocor) instead of (on-patent) Crestor. That's the flip side of these combination therapies - the insurance companies start to wonder if they can assemble the same sort of thing for a much lower price, and who can blame them? Of course, all this has already occurred to the various companies involved, who will be working hard to show that a single pill is better - that the dosing schedule makes a difference, that patient compliance is better, and so on. Everyone in this field is making sure not to miss any tricks.

AstraZeneca, for example, has been watching Merck and Schering-Plough do well with Vytorin, the combination of Zocor and the cholesterol absorption blocker Zetia, so they ran a trial of their own - Crestor and Zetia. That seems to have done very well indeed, although (as that Matthew Herper Forbes article points out), this was an open-label trial in patients with very high cholesterol numbers to start with.

But A-Z might find themselves arguing that patients should definitely go with a single pill when it's Crestor and the Abbott drug, oh yes, but to feel free to mix and match Crestor with Zetia. That'll be an interesting pitch. And things are just going to get more complicated as time goes on in this area. (Money will do that). But don't forget, the reason that there's so much money involved is that there are a lot of therapies that seem to have value. So it's nerve-wracking (but profitable) to be a drug company in this area, and it's tough to be an insurance company. But if you're a patient, well, it's not as bad as it used to be. . .

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Comments (5) + TrackBacks (0) | Category: Cardiovascular Disease


COMMENTS

1. RKN on July 7, 2006 10:05 AM writes...

I recently began taking Niacin (Niaspan) to raise my HDL and, possibly, lower my LDL. It would be swell if I could accomplish both with one pill. And there's some evidence that niacin lowers triglycerides, too, which would be triply good since mine are far too high. Tho, speaking of PPARs, I've been on fish oil for about a year, a known agonist of PPAR-gamma (alpha?), and that alone (p=0.5 ;-)) has cut my triglycerides in half!

Over-the-counter niacin and omega-3 are vastly cheaper than statins, tho Niaspan being a prescription grade niacin isn't.

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2. Novice Chemist on July 7, 2006 10:08 AM writes...

What's the difference between prescription-grade niacin and not? Is it dose?

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3. Northern Doc on July 7, 2006 10:13 AM writes...

RKN: In their studies, and it's not clear why the marketers of Niaspan (it's Oryx in Canada, I think Kos in the US) had to admit that the HDL and TG effect was less dramatic than crystalline niacin. The only benefit to Niaspan is the tolerability.

You can, however, get the same benefit with crystalline niacin if you build up slowly, and do it properly. The key is to start at 100mg per day, bump to 100mg twice daily after a week, then three times daily after another week. Thereafter, gradual increases of 100-200mg per day on a weekly
basis. Side effects can be minimized by taking ASA 81mg before each dose (45min before, to be exact) and taking each dose on an empty stomach, with a low fat snack (I suggest 4-5 unsalted soda crackers).

I have managed to get a few patients up to 1000mg three times daily, one even doesn't need the ASA. Of course, liver monitoring is imperative (like with Niaspan).

The difference between the two is that Niaspan (here in Canada anyhow) is limited to 2000mg per day, whereas crystalline niacin has been tested to doses as high as 2000 mg three times per day. The Niaspan is a delayed release formulation but is not like the prior slow-release formulations, which have a much higher risk of hepatitis. All three formulations of niacin will, to some degree, cause flushing, itching, and a sensation of raised body temperature (women liken it to menopause). Tolerability ranges (real world numbers) at about 20% for crystalline niacin and 50% for Niaspan (we don't have slow-release available around here so I can't comment on that.)

In terms of the fish oil, have you pushed it up to 3000mg per day? Or were you limited by the dreaded "fish burps"? Just curious because I have not found anyone who has managed to get up to the recommended dosing without GI intolerance.

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4. Insider on July 7, 2006 10:22 AM writes...

Ryan K - on that regimen you are guaranteed to live forever!

I, on the other hand, smoke 20 a day, drink Irish whiskey religiously and the only exercise I take is to walk behind the coffins of my friends who exerciesd every day.

This regimen is based upon an observational study of my parents who started this regimen in their twenties and continued it upto their deaths ( aged 84 and 88)!

Pip pip!

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5. Curious on July 9, 2006 9:06 AM writes...

In a somewhat related case, I'm sure everyone has heard that Merck is going to price Zocor at or below the generic competition (for example see http://marketplace.publicradio.org/shows/2006/06/23/AM200606231.html), now that it's off patent.

Can someone explain why this is considered such a 'novel' concept? Why haven't companies done this before, especially given the fact that the founding company (in this case Merck) already has a production process in place, which should be operating efficiently? Are the statins a special case due to the large market or will this trend continue as other drugs come off patent?

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