The reaction yesterday to the controversial Enhance trial, which took Merck and Schering-Plough two years to release and only after trying to monkey with the primary endpoint, was largely negative. Steve Nissen of the Cleveland Clinic went on national television to say Vytorin (which combines Zetia and Zocor) should be used as a last resort. Shares in both drugmakers fell. And Congress reiterated interest in probing the delay in releasing data.
But to some Wall Street analysts, such reactions to the trial, which compared Vytorin with Zocor, were overkill. Tim Anderson of Sanford Bernstein, for instance, had this to say in a research report today: "No statistically significant efficacy differences were seen between the two trial arms, and the safety profiles of each drug were similar...
"In isolation, the results probably would have led to a share price rise for Schering-Plough and Merck, but largely due to negative comments from prominent cardiologist Steve Nissen, share prices declined. Dr. Nissen used words like 'shocking' to describe results, which in turn predictably led to negative press reports. All industry experts we corresponded with, however, felt that this description of the results was overly dramatic.
"We have previously stated that neutral results from Enhance would likely only have a muted impact on Vytorin prescription trends given the limitations of the study, but some prescriber business may be lost on the margin contingent on much negative coverage Enhance."
And Catherine Arnold of Credit Suisse was similarly taken aback in her own research report today: "Plaque studies do not have the relevance of mortality studies, nor do they portend whether a drug will reduce the risk of cardiovascular events and death and the stock reaction was significantly overdone. The lack of a positive result in this high-risk population...is disappointing, and may delay Vytorin recovery from a commercial perspective, but does not change the prospects for the drug having a positive mortality and morbidity outcome.
"The big question is what happens to Vytorin prescription trends as competitors like AstraZeneca and Pfizer use the Enhance results to disparage Vytorin and question its benefits."
14 Comments
The "Meteor" study didnt show regression either! Its not amazing to think that medications can provide regression of any sort, in any disease state "You need a chizel to remove mortar from the walls not a water hose"
Why is it relevant that wall street analysts don't think this is very significant? Merck and Schering Plough will be downplaying this study stating that the endpoint isn't relevant, but here is my question: WHY CHOOSE IT AS A PRIMARY ENDPOINT OF A SUPPOSED LANDMARK STUDY (every trial that gets a cool acronym must be ground breaking right)? Would they be saying this if the result were a positive one? No, every drug rep would be heading into hospitals with their wheely bags to hand out reprints to any physician, pharmacist, patient willing to listen, letting them know that Vytorin is superior to those cheap, generic drugs that have been shown to decrease things like heart attacks, strokes, and death.
Mike has gotten it right. If the study wa positive, Schering-Plough and Merck would be filing with regulatory agencies for a new indication and a labeling-chenge that would permit them to shout from the highest mountaintop! Not that they would necessarily wait for official approval to do this. Their reps have been out there saying how great this new drug is at lowering cholesterol and everybody knows that reduces heart attacks and strokes. Now they have a tougher time getting docs to buy it.
Of course the Wall Street pundits aren't worried. It's not their money that they're advising people to invest. besides that, they hate to admit that they may be wrong about what they say.
It looks pretty clear to me... its a failed IMT study - which would have been a big deal in 1995, but since actual event studies are underway, it points to a possible disappointment in terms of effectiveness. This does not say whether the combination is effective or not, it just suggests that it may not be, but then again, it might not. Nissen is WAY out of bounds to declare the drug useless, and should be ashamed of himself.
The reps would get nowhere if they tried to use this trial in offices, and it would go nowhere with the FDA - its not a clinical endpoint.
The bottom line on this is - big whoop - outcome studies are following behind, and thats the only thing that counts.
SHAME ON DR NISSEN for using his "MD" to distort scientific research! This study was conducted in a population of patients that is so rare, most primary care doctors will never see. THis is NOT information that can be generalized to a regular Joe that has mixed hyperlipidemia.
I think drug companies are not interested in the actual research, just interested in promoting their drug through clinical trials.
Who are the cardiologists waiting for these results, I certainly hope they don't take these studies seriously.
perhaps, it takes a couple of years to come up with a positive spin ,(reminds me of the elections, but this is scientific research not politics??)... don't know.
change the endpoint?(explains the independent reviewers. subsequently very dependent reviewers).
who lets these drug companies get away with this?
EJH,
You have no idea what you're talking about. Dr. Steve Nissen is a good physician and a good man. I'd trust him with my life twenty times before I'd trust Fred hassan or Dick Clarke with the care of my dog! The companies chose the population they did because it was the best population to show an effect in. They, plain and simple, blew coming clean on the study when they knew there were problems. In the meantime, they made bindles of money. Only an investigation will find the facts - emails, memos, testimont, review of the books, etc. - it all should be done.
Paul,
The companies did this study because they thought it would work and they would have an additional windfall of money made possible by another indication. It was done for a submission to regulatory authorities to obtain a new indication - a scenario that has been followed with all of the statins. The history over the past 20 years has been that success has been routine, but ENHANCE failed.
While it doesn't mean that the drug won't impact events, but we won't know that answer until 2011 when IMPROVE-IT completes. Given the recent events, we may not know until 2015! What it does mean is that physiciians should think long and hard about giving a $100/month treatment vs. a $20/month generic treatment if the evidence doesn't demonstrate otherwise. Of course, for statin-intolerant patients, zetia is always an option. if you want to stick with proven therapies, then use niacin of a resin for more cholesterol reduction. Both of these are inexpensive as well.
Nissen has been discouraging use of ezetimibe all along. You can look at statements he made when the drug was first approved. Heterozygous familial hypercholesterolemia has an incidence of 1/500 on average, so most doctors have seen it. Some people have not been diagnosed, of course, and there is an overlap of the LDL level distribution between people with heFH and people without. To make things more complicated, not all mutations that cause it have been identified. I agree that the ENHANCE results do not prove that ezetimibe does not reduce the risk of cardiovascular events, but they certainly don't inspire confidence. Since statins have proven benefit, I see no reason to use ezetimibe except for people who cannot tolerate statins and whose risk is fairly high. Possibly you might use it as an add-on to a statin if the person could only tolerate a low dose of the statin and their risk was high.
These Wall Street guys don't have any idea what they're talking about. The results of ENHANCE were devastating for MSP. They had the next two years of promotion all planned out with a new indication for reducing the progression of atherosclerosis, but the trial was a complete failure. They won't have any new information on ezetimibe until 2011 at the earliest, but the way that they do and report trials, it may be 2015. Just in time!
This study was done to examine Hyterozygous Hyperchol patients because they are the HIGHEST risk group that would show the greatest benefit. IF YOU CAN'T SHOW BENEFIT HERE who do you think will benefit?? This population could do almost anything postive and find some kind of benefit.. but to trend in in opposite direction!! ahhh that is a hugh RED FLAG! I agree that mortality studies have to be done but please don't enroll anyone I know (and care about).
This is much, much worse than just not showing differences over the generic versions of this drug.
From the NY Times article: ************************** The Enhance trial was meant to prove that Vytorin’s combination of Zetia and Zocor would reduce the growth of fatty plaque in the arteries more than Zocor alone. Instead, the plaque actually grew almost twice as fast in patients taking the combination.
Reducing plaque growth is crucial, because plaque formation — known as atherosclerosis — can lead to the blockages and blood clots that cause heart attacks and strokes, said Dr. Howard N. Hodis, a cardiologist at the University of Southern California. That is why the trial’s finding is worrisome, Dr. Hodis said. **************************
SO, while Merck and Schering-Plough sat on these results their heavily profitable drug cocktail was, in fact, SIGNIFICANTLY INCREASING THE RISK OF A HEART ATTACK in patients for whom it was prescribed. This is criminal behavior, not just PR spin for profit. These companies should be held accountable.
Dusty, You say: "their heavily profitable drug cocktail was, in fact, SIGNIFICANTLY INCREASING THE RISK OF A HEART ATTACK"
Do your homework. The difference between the two groups was not statistically significant. There was no significant difference in cardiac events between the two groups.
Your statement may be true, but no one will know if it is for many years. Certainly no one at Merck or SP knows if your statement is true or not. Once the trial is complete, then we'll know.
I wonder if any of the financial uys helped Carrie Cox with her stock option decision?