Results Of Merck’s Vytorin Trial Delayed A Year
7 CommentsBy Ed Silverman // January 11th, 2010 // 7:44 am
The drugmaker says that completion of the much-anticipated IMPROVE-IT study will now take place in mid-2013 instead of mid-2012 due to the pace of enrollment, the “accumulation of clinical endpoints to date” and 30 months of follow-up needed, according to a statement. Merck hopes the study, which began in 2005 and has so far enrolled about 16,000 patients, will show that its Vytorin cholesterol pill can outperform Zocor in preventing deaths, heart attacks and strokes. Vytorin combines Zocor with Zetia.
Improve-It is supposed to resolve questions raised by the Enhance trial, which found Vytorin failed to show a benefit over the much cheaper Zocor in reducing plaque in the carotid artery, and showed a statistically insignificant buildup. Vytorin did a better job of lowering LDL, but fared no better than an inexpensive statin in patients with familial hypercholesterolaemia, an inherited form of high cholesterol.
However, Merck says the results could yet be completed sooner than 2013….
According to Merck, “the Data Safety Monitoring Board will conduct an interim analysis for efficacy later this year when about 50 percent of the pre-specified (5,250) clinical endpoints have occurred. In addition, the IMPROVE-IT executive committee and Merck have developed a plan for the DSMB to conduct an additional interim efficacy analysis when approximately 75 percent of the pre-specified endpoints have been reached, which could result in an earlier completion of the study.”
In an investor note, Leerink Swann analyst Seamus Fernandez writes the study could be completed “as early as late 2011 or early 2012, due to a new interim efficacy look. Merck will publish a paper online in the next few weeks highlighting the statistical plan for a second interim efficacy evaluation…with an accompanying editorial by Dr. Robert Califf of Duke University…We believe the second interim look is primarily motivated by the controversy surrounding IMPROVE-IT along with a desire to provide an answer to participating patients and physicians as quickly as possible.”
“Zetia/Vytorin contributes roughly 10 percent of global sales…We believe the second interim look is primarily motivated by the controversy surrounding IMPROVE-IT along with a desire to provide an answer to participating patients and physicians as quickly as possible. A key fact, however, is that IMPROVE-IT will not be stopped for futility, only evidence of benefit or harm. We do not believe that Zetia is harmful and expect the study to go to completion,” Fernandez concludes.
See more coverage in The Pink Sheet (full disclosure: Ed Silverman is an editor at The Pink Sheet).
Dan
This sounds like a sequel to the ENHANCE trial.
Salmon
There’s great additional information on this in a post on Shearlings Got Plowed.
http://shearlingsplowed.blogspot.com/2010/01/merck-provides-updated-mid-2013.html
The most important information is that Merck’s CEO seems to have implied that the study will not be stopped even if they know the drug will not improve outcomes.
Clearly this is unethical as there are safer (i.e. no rhabdomyolysis et al.) and effective drugs currently available.
Allowing unethical studies to run (it happens all the time) is unacceptable and FDA regulations need to be changed.
Also did you know that that the FDA can’t stop a study for inadequate informed consent as this is left to the institutional review board.
Consequently there are studies where there is a known risk was death and yet the informed consent does not mention it and the FDA is helpless to stop the study. In light of posts such as the following
http://www.pharmalot.com/2008/12/time-bomb-the-clinical-trial-gold-rush-in-india/#comment-457515
Regulations to prevent trial subject endangerment must also be strengthened.
The FDA has the legal obligation to ‘protect the public health’. I believe we the interested and knowledgable readers of this blog should let FDA Commissioner Hamburg that these policy of doing nothing to protect patients are unacceptable and need to be changed.
Her address is:
Commissioner Margaret A. Hamburg, M.D.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
OFFICE OF THE COMMISSIONER
10903 New Hampshire Avenue
WO1-2217
Silver Spring, MD 20993-0002
and her is e-mail.
margaret.hamburg@fda.hhs.gov
I would also cc Senator Grassley.
Senator Chuck Grassley
135 Hart Senate Office Building
Washington, D.C. 20510-1501
If you e-mail Commissioner Hamburg you can copy Senator Grassley by cutting and pasting the e-mail into the following webform.
http://grassley.senate.gov/contact.cfm
I would however advise letters instead.
Salmon
Condor
Thanks, Salmon — Of course, I agree with all of yours.
I will note that — in my opinion — the results of IMROVE-IT, even if completed, won’t be published until late 2014 or 2015. The analysis on that conjecture has been “out there” since November of 2009 — simply by piecing together the already public data.
So — with Vytorin (albeit in smaller studies, with largely only surrogate endpoint analysis) running on an 0-for-3 track record (ENHANCE, SEAS and ARBITER 6 - HALTS). . .
When does the professional independence of the prescribing doctor kick in to say — enough, already?
Great stuff, Ed!
Namaste
Salmon
Thanks,
I neglected to add that in the case of the Vytorin Improve-IT study that it’s not only unethical in respect to patient safety but in my opinion it’s also a way for Merck to unjustly enrich themselves.
If they know the results are negative and if released will likely result in decreased prescribing then they are making sales including those paid for by the US gov’t that they shouldn’t be. To me this is fraudulent and I would assume that this additional information would be of interest to Senator Grassley as ranking member of the Finance Committee.
Salmon
Salmon
Another note FYI
http://shearlingsplowed.blogspot.com/search?q=FDA+transparency
“18 USC ยง 371. Conspiracy to commit offense or to defraud United States
If two or more persons conspire either to commit any offense against the United States, or to defraud the United States, or any agency thereof in any manner or for any purpose, and one or more of such persons do any act to effect the object of the conspiracy, each shall be fined under this title or imprisoned not more than five years, or both.”
Seems to me that per Condor’s earlier post mentioned above that MERCK CEO Clark has indicated that he has already conspired to defraud the US. Thus it seems that it’s a question of whether an act to effect the conspiracy has been commited yet or not. It’s possible that simply not having stopping criteria for futility might fulfill this.
Salmon
Paul
The lipid hypothesis is on its last leg as the pharmaceuticals look to squeeze just a few more billion out of the statin hobby horse. On average people with higher cholesterol live longer.
http://healthjournalclub.blogspot.com/2009/10/do-people-with-high-cholesterol-live.html
Big Pharma Watch
No doubt the first of at least a few delays for these results! I wouldn’t even bet a dime that they’ll make these revised timelines. Just milk the drug for all you can before it goes off patent. After that, nobody at Merck will care and neither will Wall Street.