Fred Hassan Sidesteps Vytorin Cancer Risk
23 CommentsBy Ed Silverman // July 21st, 2008 // 7:03 pm
What cancer scare? That was the deft touch the Schering-Plough ceo had when asked on a teleconference call today with Wall Street analysts about the news that the so-called SEAS trial found an unexpectedly higher rate of cancer in Vytorin patients than those given a placebo.
Instead of mentioning the ‘C’ word, Fred focused on a secondary endpoint - a statistically significant 22 percent reduction in non-fatal heart attacks and coronary artery bypass surgery. Never mind that SEAS failed to meet the main goal of improving cardiovascular outcomes for patients with aortic stenosis, which is an irregular thickening of the main valve to the aorta.
“What I took away is that this study confirmed the results from other cholesterol lowering agents that reducing LDL does not reduce the rate of progression of aortic valve disease,” he told analysts. “Vytorin had positive outcome data, reducing the risk of coronary artery disease in these patients.”
But what about cancer? “I’ll leave the interpretation of the science to the independent scientists.”
Chuck Grassley, however, is having none of it. He sent yet another round of letters to Fred and his counterpart at Merck, Dick Clark, who have a joint venture to market Vytorin, because the drugmakers have yet to fully respond to earlier inquiries. The SEAS “study itself may make the situation uncertain or even more confusing. But one thing is clear and that is that the drug maker hasn’t been responsive to Congress and ought to be given the public safety and public expenditures involved with Vytorin.”
Piper
Well, if you had listened to the 2 hour call and read the follow-up cancer analysis by Oxford, you too would wonder what cancer risk the media is trying to get all hyped up about.
Marilyn Mann
“I’ll leave the interpretation of the science to the independent scientists.” Excellent idea, Fred! You finally said something I can agree with!
Ed Silverman
Hi Piper,
Just for the record, I did watch the webcast from London earlier today. At first, Pedersen’s presentation of the cancer finding was rather dramatic. And so I led my post with that point, although I later modified the headline and, of course, added more info as it was presented.
Beyond that, I won’t pretend to play epidemiologist and argue the merits of the cancer findings one way or the other, but I do wonder about the notion of combining all three studies - SEAS, SHARP and IMPROVE-IT - while the two big trials are still under way to reach a conclusion.
Anyone have any thoughts on the extent to which that is sufficiently insightful or definitive?
Regards
ed
SP 2
There are potential issues here. SEAS was done in patients with AS. SHARP is being done in patients with renal disease. IMPROVE-IT is to be the final word, but not available for some time. I understand that SHARP is fully randomized, so the patient years is probably fine. It is puzzling that they looked at IMPROVE-IT given that it’s such a young trial and is not fully enrolled. I think Sir Richard Peto had to become involved in order to save the trial that he is connected with. he doesn’t want calls for closing it down!
Nathan
Hold on folks — the larger clinical trials did not show an increased risk of cancer, right? Why would you trust the results from a SMALLER trial?
Lisa Van S
Hey, Nathan!! Why dont you disclose who you truly are?.. The Pharma Retort Reporter. You are an “Industry Hack”, and anything you SAY SHOULD BE TAKEN WITH A GRAIN OF SALT.
Bob Freeman
Ed, I haven’t read the details so this reply could be way off. It’s fairly standard to conduct meta-analyses of clinical trials. This allows you, following a standard statistical protocol, to detect rare (and not so rare) events from the combined population. In the end you get either an odds ratio or relative risk ratio and determine significance. The rules for conducting a meta-analysis are fairly rigid when done well.
Lisa Van S
Bob,
This isnt the only Med that showed an increase for cancer,. Others showed a high risk of “Breast” cancer. I apologise for not elaborating!! Funny thing,.. rules pertaining to discovery,.. the “Law” you know!
Ed Silverman
Hi Bob,
I understand that a meta-analysis is a regular activity. In this case, the two larger trials are not yet completed, as far as I can tell. So I’m just wondering about blending those two trials with the SEAS trial, small or not, to decide today that cancer is not a risk.
Cheers
ed
Pharmacritique
No idea about cancer.
But I don’t understand why SEAS is too small when it comes to adverse events like cancer, but large enough to prove a preventive effect in coronary outcomes.
Justice in MI
To the extent I know anything about this (which is very little), what Bob says makes sense about meta-analyses.
So, also, what Nathan says about larger versus smaller studies.
My own “concern” is that it has the “feel” (I guess if you’re oriented) of a kind of data scramble to find off-setting numbers, particulalry in light of what SP2 said about drawing on IMPROVE-IT at this stage in the game.
Of course, you want to have whatever data is available - this is important business, to say the obvious. So we do, indeed, have to wait for the epidem/stats people to say whether these different studies _can_ be combined, at this point, to create a realistic meta-analysis.
So that is taking Hassan at his word - he really can’t say right how meaningful (or not) is this signal from SEAS. But I think we can say it is a signal.
Bob Freeman
Just an opinion, Justice: reading and rereading the PR release didn’t provide me with any better understanding of what might be going on here. I agree with you–about the only thing I can conclude is that a signal has been observed.
Brought back painful memories of working with PR people on press releases on research findings . . .
SPRI 2
There is no question that the cancer results in SEAS go the wrong way for Vytorin, but are they real. I’m sure that SEAS was not sized to look at cancer events, so the significant differences between groups are a surprise. Are they real or not? The analysis that was done including patients from on-going trials is designed to counteract the potential damage of the cancer finding. I understand looking at SHARP, but why IMPROVE-IT when most patients haven’t been in any more that 6-12 months? It looks like it may have been to pad the numbers. I wonder what SHARP alone indicates? This is the study that Sir Richard Peto is involved with and surely wants to save,
BPW
Fred Hassan is a spin man, but he used to be a spin master. It seems that recently he has lost his touch. Or perhaps he’s in over his head with turmoil at SP ! So much for the pharma savior. More and more he’s looking like SP’s curse! No wonder he’s hiring PR and IR advisors every time we turn around.
Justice in MI
This from tomorrow’s/today’s New York Times on SEAS and the other two studies:
“But other doctors said the data from Improve-It and Sharp were not definitive. The patients in those trials have generally been followed for one to two years, while the Seas trial followed patients for four years. Because cancer generally takes years to develop, it may take some time for Vytorin’s risks — if they are real — to become evident in patients.
“I don’t know that you have much information about the cancer risk from the other two trials,” said Dr. Bruce Psaty, professor of epidemiology at the University of Washington.
In addition, the other two trials contain a puzzling finding. While the number of cancer cases is similar in those trials among patients taking Vytorin and those who were not, the number of cancer deaths is approximately one-third higher among those taking Vytorin. In all, 136 people taking Vytorin have died of cancer in the three trials, compared with 95 taking other medicines or a sugar placebo pill.”
Insider
Talking about a secondary endpoint when the primary was insignificant.
I dont think SP’s reps would be allowed to do that - so why should Fred get away with it!?
Vince
“The bottom line is there was a trade-off in this trial — in a reduction in some cardiovascular events and an excess of cancer deaths. It’s obviously not a favorable result,” said Dr Steven Nissen, chairman of cardiovascular medicine at Cleveland Clinic, who has been critical of Vytorin use in the past.”
About sums it up from Reuters
” Vytorin fails to meet main goal of heart study
07.21.08, 3:28 PM ET’
Doc
Fred,
Doc
Fred,
You can do better than that! CV risk reduction?! I believe we know that from your simvastatin component. Go read the 4S study from 1998.
Piper
The most unique point about SEAS (vs. almost every other cholesterol-lowering trial to date) is that it was done in the elderly population (70-85). In the last (and perhaps only) large scale trial done in the elderly population, PROSPER, pravastatin showed a 25% increase in cancer death vs. placebo. Likewise, the SEAS trial involved an elderly population, and showed an increase in cancer subsequent to reductions in TC. How was the increase in cancer explained away for PROSPER? Meta-analysis of other statin trials were done and showed no increase in the risk of cancer (but there were no other statin trials in the elderly to compare to….and there would be no more since then). If meta-analysis is good enough for statins, it should be good enough for the rest.
On a side note, Pfizer recently completed the TASS trial - Lipitor in aortic stenosis. According to the AJC, “Patients prognoses were worse than expected, w/ 51% experience major adverse clinical events [and] does not support the concept that treatment with [statins] halts the progression of aortic stenosis”. Hmm, why didn’t this make the NY Times??
Ed Silverman
Hi Piper,
Just for the record, I did note - albeit very, very briefly - the results of the TASS trial you mentioned early last week. You can see that here…
http://www.pharmalot.com/2008/07/vytorin-update-preliminary-study-results-today/
I don’t know why the NYT didn’t mention it, but any time a new study debuts that has something compelling, feel free to let me know.
Regards,
ed
Piper
Ed,
I’m just as bad as the NYT for not noticing your mention of TASS last week. My fault. I stand corrected.
Cheers,
Piper
VTX1300
On a positive note, look for RAAVE Trial, Journal of the American College of Cardiology. Volume 49, No 5, 2007.
Conclusions: Prospective treatment of aortic stenosis with rosuvastatin by targeting serum LDL slowed the progression of aortic stenosis. This is the first prospective study that shows a positive effect of statin therapy for this disease process.
I guess Fred H. was unaware of this Trial, and the W.S.J. missed it as well.
Let’s see negative Lipitor Trial, positive Crestor Trial……