Click image to enlarge.Have you seen this new Crestor print ad from AstraZeneca? Crestor is one of the newer anti-cholesterol drugs that recently gained the right from FDA to claim it slows the progression of atherosclerosis (plaque buildup in arteries). That new indication is clearly the focus of these ads, a sample of which -- taken from the February 4, 2008, issue of Time Magazine -- is shown above.
Recall that with all the hullabaloo over Vytorin/Zetia and the failure of the ENHANCE clinical trial (see "Should I Stop Taking Zetia?"), Merck and Schering-Plough have pulled direct-to-consumer (DTC) ads for these products from TV. I haven't seen any Crestor ads on TV lately either.
As I suggested previously, I believe these ads will be back on TV after Merck/Schering figure out how to spin the benefits of Vytorin/Zetia in light of the failure to demonstrate any effect on plaque. Clearly. they will have to make a case that LDL cholesterol is the leading cause of plaque buildup in arteries even though this wasn't proven by the ENHANCE study.
But NEW Crestor TV ads -- like the print ads -- will be able to bypass the cholesterol-lowering message, which consumers now suspect is the lesser benefit compared to lessening plaque buildup (see "Cholesterol Drug Users Discuss Their Medication").
The basis of Crestor's FDA-approved claim that it "slows" plaque buildup is data from 876 patients in the "METEOR" -- Measuring Effects on Intima Thickness: An Evaluation Of Rosuvastatin 40 mg -- study (see excerpt for the Crestor PI below).
Click on image to enlarge and read.The interesting difference between this study and the Vytorin Enhance study is that it compares Crestor to NOTHING (placebo) whereas the ENHANCE study compared Vytorin to simvastatin, the generic version of Zocor, which is the non-Zetia component of Vytorin.
See, folks, this is why the drug industry doesn't like to do "head-to-head" clinical trials that some critics say need to be done to justify the extra expense of newer drugs compared to older ones.
Note the IronyThe take-away message from the METEOR study is this: 52.1 % of the Crestor-treated patients in the study demonstrated an "absence of disease progression," compared to 37.7% of patients in the placebo group. That's a net difference of 14.4%. So, of the 876 patients studied, 126 more were helped by Crestor than by placebo. Or, to use the number needed to treat (or NNT) statistic (see "The Statin Lottery: Number Needed to Treat Statistic"), for one person to benefit from Crestor, about 7 people have to be treated (NNT=6.95). Still, we're only talking about "absence" of progression of plaque buildup, not prevention of heart attacks, which is the ultimate endpoint.
The ENHANCE and METEOR studies are similar in one respect: each studied only a few hundred people over a limited time period. Merck and Schering-Plough are trying to say we shouldn't place too much emphasis on a clinical trial involving only a few hundred people. Yet, a clinical trial involving only a few hundred people was good enough for the FDA to approve a new Crestor indication worth hundred of millions of dollars to AstraZeneca!
Love it John!
ReplyDeleteThe irony is perfect.
Simvastatin is generic Zocor. Lovastatin is generic Mevecor.
ReplyDeleteThanks. I meant to say Zocor, not Mevacor -- correction made.
ReplyDeleteCrestor actually reversed athersclerotic plaque in the coronary arteries (as measured by IVUS) in the Asteroid study. Crestor still doesn't have an indication to do that, but the results were impressive. As for the number of patients in Meteor, a study either yields statistically significant results or it does not. Meteor did. The
ReplyDeleteENHANCE study was more than sufficiently powered (with around 700 patients) to yield statistically significant results in a surrogate marker type study. As for ENHANCE's patient population, the heterozygousfamilial hypercholesterolemic pateint population grows plaque quicker than any other group. That's why MSP selected this type of patient. The 17% LDL spread should have produced some difference in plaque progression. We learned from torcetrapib that it wasn't just raising HDL, but how you raise HDL that apparently makes a difference. Perhaps ENHANCE has taught us that how you lower LDL makes a difference too. Regardless of what you think of the study or Zetia, MSP's behavior has been inexcusable throughout this entire ordeal. Regarding head to head Studies, Prove-It, IDEAL, and ENHANCE may have Pharmaceutical companies thinking twice before they do their next head to head trial..lol Can't wait to see the SATURN (Lipitor vs. Crestor) results...lol If the pattern of the company setting up the study losing continues, AZ better watch out!
John, I thought you might find this interesting. Brandweeknrx.com has found cafepharma postings that indicate SP employees new about the results of ENHANCE as early as March 13, 2007. This would be only a few weeks before Carrie Cox sold her stock. It also strongly hitns at why MSP pulled the ENHANCE results from the ACC at about the same time.
ReplyDeletehttp://www.brandweeknrx.com