Today’s NY times gets very excited about the ability of statins to lower cholesterol and therefore reduce the risk of heart disease. In particular they cite the improvement you get from getting LDL below the consensus "normal" levels. Of course as the article called Just how low can you go? points out, this is great news for the statin makers.  Only around 10% of those who seem to be indicated for statins are actually taking them.  On the other hand scaremongers (i.e. this blog and others) keep pointing out that there can be side-effects from statins, which include severe muscle pain and some say long-term amnesia.  While it’s OK for the NY Times to act as Pfizer’s PR company on occasion (and this may actually be one of them), and to correctly point out that the incidence of side-effects is very, very low, they might have noted another study out yesterday.  That study, in the British Medical Journal suggested that a new blockbuster drug you may have heard of called aspirin was found equally efficacious and far more cost-effective in preventing heart disease than statins. And not just a little more, but by a factor of 20.

The full paper admits that aspirin use does have side-effects (usually stomach bleeding), but obviously, as in the case of the Cox-2 inhibitors, the patients could be started on that regimen and switched to statins if they can’t handle the aspirin.  Overall this study should give pause to the statin manufacturers.  In the UK where the government already concedes that its paying too much for statins and is trying to move them OTC, this could be the start of a movement to replace them with a rather more mature and much cheaper product! In the US where cost-effectiveness is not a recognized concept, don’t expect too much attention to be paid. But as we eventually (i.e in ten years time) move into an era where the government and public starts to expect value for money from drug companies as well as miracle cures, this type of analysis will become more common and more important.

As you probably know by now, the UK has a national health service (NHS) which pays for prescription drugs. Most Brits pay a small (or if they are over 60 no) co-payment when they get their drugs and the real cost of the drugs are absorbed by the government. The government does indeed bargain down the price of the drugs, but there is still a real cost involved. Just like health plans in the  US, where Wellpoint led the battle to get Claritin forcibly moved to the OTC market, the UK is interested in moving drugs OTC–where of course the cost is absorbed directly by the consumer. 

Now, one of the most significant categories is moving in that direction. Currently the NHS is spending roughly $625 per year for each of the 1.5 million Brits on statins–more proof as if you needed it that we Brits eat too much greasy food!  At over $900m a year, that’s a tempting morsel to get off the government’s budget, and consequently the health minister is looking to move statins to OTC in the UK within 6 months.

Merck is thrilled about this as its main statin Zocor lost its patent in the UK earlier this year–it has patent protection in the US until 2006.  Pfizer has less to worry about in the US as Lipitor is patented until 2010. However, in the UK presumably if Lipitor comes out of the NHS’ (and in some cases out of fundholding GPs’ budgets), and Zocor is availble OTC, this is bad news for Lipitor as physicians there will stop prescribing it, and instead tell patients to get Zocor at the local chemist. Of course, Merck and its OTC competitors will meet stiff price resistance there. At Drugstore.com Liptor is about $1100 a year in the US, but less than half that in Canada, and obviously will cost much less OTC in the UK. So this might be a fore-runner of what happens in the US when Zocor goes off patent in 2 years. And of course if Zocor is operating successfully OTC in the UK by then, why wouldn’t US health plans want to move it and Lipitor OTC here too–just as they did with Claritin?

Crestor Update.  The newest statin Crestor from Astra-Zeneca has had a somewhat rocky start.  In this post I noted that the  research group Friedman, Billings, Ramsey & Co had suggested Crestor wasn’t selling too well and that there were some adverse events being reported in the UK.  Now that same group has reported that according to:

The Canadian Adverse Drug Reaction Monitoring Program, a database maintained by the Therapeutic Products Directorate of Health Canada (the drug regulatory agency in Canada), between February 1st and September 30th, 30 adverse drug reactions have been reported with Crestor, 24 of which were considered serious. In addition to 10 reports of muscle-related side effects (eight at the 10mg strength and two at 20mg, with eight patients below the age of 60) and one death (myocardial infarction in a 22-year-old patient), we find it notable that kidney-related adverse events have been associated with the drug at lower dosages. Events associated with kidney issues were observed in five patients in Canada and are as follows:

? one report of acute renal failure at the 40mg strength;
? one report of nephropathy at the 10mg strength;
? two reports of proteinuria at 10mg;
? three reports of hematuria, one at 10mg and two at the 20mg strength;
? two reports of increased blood creatinine, one at 10mg and one at the 40mg strength.

Of course it’s still very early days for Crestor, but between these reports and the suggestions of rushing the research in The Lancet last month, it may be that the FDA starts to consider some action.

So I can’t quite stay away from the Bill….

In a reminder of how hardball politics is played in the USA these days, there’s a report out today (hat tip to California Healthline) that shows that in the first 6 months of 2003 the healthcare industry spent over $139m on lobbying in the run-up to Medicare bill. $37.7m came from the pharma industry. This number probably includes standard costs associated with keeping Washington offices, etc. so it’s not all "new" money. But obviously much more has been spent in the last four months, and there’s no doubt that, as in its successful attempt to defeat certain House Democrats who were in favor of price controls in the run-up to the 2000 elections, targeted contributions and lobbying have had a definitive pay-off for the pharma industry in this Bill.

This is no secret in health care.  The AHA, for-profit hospital groups and the AMA have been doing this forever in order to influence the Medicare and Medicaid reimbursement schedules.  The drug companies have too, of course, but as they were previously opposed to drug coverage, their contributions weren’t quite so targeted.  Now that the industry has decided to buy the best bill it can, you can see the results in the text of the bill–especially the import ban from Canada.  The ongoing federalization of the health care system continues.  It’s starting to look more and more like the Defense department and the military industrial complex–you can expect the lobbying/business techniques in that industry to become more common in health care.

This post is not meant as criticism of PhRMA.  Their fiduciary interest is to their shareholders, and once they saw that politically drug coverage was unavoidable, that interest means to get as much money as possible out of the government. And the way to do that in the USA is by using money to buy influence. In the light of the even more pork-laden energy bill coming out the same week–and you know that there was equal lobbying weight on that one too–more disinterested observers may believe that campaign finance reform needs a little strengthening. But that’s in a parallel universe and we and PhRMA live in this one.

In my recent post about Cox-2 inhibitors, I suggested that pharma companies had been successful in getting them widely adopted, and that conversely PBMs and payers had done a bad job in counter-detailing. One doctor emailed me suggesting that I had overlooked the importance of defensive medicine–the desire of the doctor to avoid a law-suit. I challenged him to show me a lawsuit for prescribing ibuprofen and here it is, and the suit came from only one dose of ibuprofen.

You may feel that this overly stresses legal pressures on doctors’ prescribing. However, while the patient lost the lawsuit, and it was a pretty extreme case, there is clear evidence that some other medications have been marketed this way.  Genentech marketed TPA for heart attack victims by stressing that if a marginally less effective but much cheaper drug (Streptokinase) was used instead, legal ramifications would follow from patients’ families if the patient died. A large clinical trial had shown that there was a slightly better chance of patient survival if TPA was used.  TPA use became the norm very quickly. This might explain some of the COX-2 "over"-prescribing.  Of course, DTC advertising and poor formulary enforcement helped too

Arnold Relman, former editor of the NEJM and long term opponent of for-profit health care, has an op-ed piece in the NY Times complaining about the  impact of pharma companies sponsoring CME. Relman suggests getting pharma companies out of CME.  This is an old chestnut from Relman and I wouldn’t usually link to this other than to note that while the pharmas throw alot of mud at the CME wall, they’re not too sure whether it’ll stick–and it’s done as much as part of a competitive arms race than based on  too much pure marketing science.

But Donald Johnson, who’s really getting into his stride after a few quiet weeks at The Business Word has a more interesting, free-market suggestion: Have the payers pay doctors to attend counter-detailing CME sessions!

While the PBM stocks have been going up, the same thing is happening to the big pharma stocks, as you can see in this chart of a pharma stock index , and in the performance of Merck’s near 10% surge in the last 3 days. There’s more in this Forbes article.

However, the legislation may have been sent out from the conference committee, but it has three major pieces undecided. These include the issues of competition, long-term cost control and Health Savings Accounts.  If they couldn’t get a solution out of the two moderate Democrats on the committee, is there really a chance that this will get past Ted Kennedy? Lefty economist Paul Krugman explains why not.

So I’m still pondering shorting the PBMs…..

When I first saw this headline: Pfizer’s Lipitor Stops The Plaque, I misread it and thought that it said Lipitor stops "plauge"–now that would be a hell of an off-label use!

Remember the movie Trading Places when two rich old men put Dan Akroyd into the gutter and take Eddie Murphy out of it to figure out whether it’s nature or nurture that affects people’s outcomes?  Well there’s an equivalent going on in the Pharma industry right now. In this article, Fred Hassan’s Clean House, Forbes reports that almost all Schering-Plough’s management team have now followed him over from Pharmacia.  You may recall that Hassan went to Schering when he had a bit of free time on his hands, having very successfully sold Pharmacia to Pfizer for $58 billion in 2001. But you might also recall that at Pharmacia, Hassan had good drugs like the blockbuster Celebrex, Bextra , and some strong  therapeutic franchise’s elsewhere.

Now the whole team is over at Schering they’ll see whether they can make a success of going from the penthouse to the gutter (relatively speaking of course!).  Schering isn’t quite out of revenue or products but it will be nowhere near as easy a management job for this team as they had at Pharmacia. It reminds me a little of the Dilbert cartoon when the pointy haired boss announces to Dilbert and colleagues that "We always say that people are our most valuable asset, but I just did an audit and found that money is our most valuable asset–people came in 9th." Now Hassan and his team can prove that it is people not blockbuster product that can move the stock price.

Oh, and in Trading Places Eddie Murphy shone in the penthouse and Dan Akroyd (initially) fell to pieces in the gutter, showing that nurture or environment or, in pharma terms, product was the determining factor!

There’s a little more info about the adverse events with Crestor, in a report called What’s the Matter with Crestor? from Friedman, Billings, Ramsey & Co Research. (I couldn’t find a way to get the report without opening a brokerage account!).

The research suggests so far that Crestor is not doing as well in the marketplace as was expected, and is being outpaced by Schering & Merck’s non-statin, LDL-lowering drug Zetia, which can be taken in addition to statins or by itself, and is useful for at least the 5% of population that cannot tolerate statins. The report says

Translation for non-pharma folks is that Crestor hasn’t taken up as well as it might have done. Meanwhile the report also goes onto to confirm some of the issues around safety. You’ll recall that Public Citizen, and The Lancet have been bringing this issue to the forefront.

I repeat that I am not a scientist or physician and have little understanding of the seriousness of these findings.  However, 35 of 45 muscle problems were reported on the 10mg dose– 1/4 of the dose that concerned The Lancet, and there were three reports of increased Creatine Phosphokinase which is a precursor to rhabdomyolysis. The question is whether the medical community views this as minor or whether they perceive that these very initial results are indicators of more trouble to come.