Vytorin Follow-Up Trial Delayed ‘Til 2012

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deadlines2.jpgNo, this isn’t the trial to be revealed and dissected at the American College of Cardiology conference in Chicago this weekend. That study, called Enhance, was already completed - and caused a huge ruckus (back story). But Schering-Plough and Merck, which jointly market Vytorin, hope to prove that a larger study dubbed Improve-It will show their cholesterol pill can outperform Zocor in preventing deaths, heart attacks and strokes.

Initially, the trial - which enrolled its first patient in 2005 - was to have examined approximately 10,000 patients, but is being expanded to include about 18,000 patients in order to have a large enough sample size to measure risk, according to a statement by Eugene Braunwald of Brigham and Women’s Hospital, who is chairing the trial. As a result, the results will be reported in 2012, instead of 2011. However, they say this is an estimate, which means the trial could keep rolling until Vytorin US patents start to expire in 2017. By then, disappointing news is less important to the sales effort.

Researchers have been awaiting the results of Improve-It 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 even showed a statistically insignificant buildup. And while it did a better job of lowering LDL, the pill fared no better than an inexpensive statin in patients with familial hypercholesterolaemia, an inherited form of high cholesterol. Vytorin combines Zocor with Zetia.

The Enhance trial, however, stirred controversy because of how the drugmakers handled the study - a two-year delay in releasing the data; a brief change in the primary endpoint without consulting the lead investigator, and huge stock sales by some Schering-Plough execs. As if to emphasize a hands-off approach this time, today’s announcement was made by the academics at Brigham and Women’s and Duke University who are overseeing the trial, not the drugmakers. A Schering-Plough spokesman says the two groups recommended the change, which the drugmakers “accepted.” Of course, releasing any Vytorin news late on a Friday afternoon - when news often goes unnoticed - doesn’t inspire confidence.

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  1. [...] Forest University Vytorin Follow-Up Trial Delayed ‘Til 2012 » This Summary is from an article posted at Pharmalot » News, Comment and Conversation on Friday, [...]

  2. You say the Vytorin patent expires in 2017; Rost says 2013. Which is it?

  3. Hi John,

    There are different Internet sites listing 2013 and 2014, in fact. I asked the Schering-Plough spokesman and he says 2017. I then asked him to clarify the discrepancy between his response and what I’d seen on the Internet. He has not yet replied. There are different patents involved, as you know. I am also waiting to hear from an industry analyst. If the info provided me needs to be clarified, for whatever reason, I will do so.

    Hope this helps,
    ed

  4. Ed,

    Patients with heterozygous familial hypercholesterolemia do not necessarily have heart disease. That have very high LDL, which is a risk factor for heart disease.

    ENHANCE looked at carotid intima-media thickness, not carotid artery plaque.

    Marilyn

  5. Hi MKM,

    Thanks. I modified the language. Sometimes, the effort to keep things simple either oversimplifies or clouds the picture. Hope this makes more sense now.

    ed

  6. They may well keep this trail going until the patent has expired . Enhance showed no benefit and if this is repeated here then the relationship of LDL to CVD will bear a closer look but only after the proper time period.

  7. Vince,
    If they do prolong the trial like that, it will the drive the reps to a homicidal fury at management. I used to sell Lipitor, and it killed us, just KILLED US, that we didn’t have any morbidity and mortality data for so long. Docs, cardiologists especially, didn’t just want lowering, they wanted endpoint data. I am long out of the CV field, but I suspect the Vytorin reps are hearing “Show me the data!” Not only that, but without endpoint data, they may have a hard time justifying preferential formulary placement, especially after atorva goes off-patent.

  8. These trials are twisted, extended, end points changed, analyzed by shills too frequently. How about a fund all pharma pays into for NIH to decide what needs to be studied and run the trials. Enhance should be a wakeup call to even the biggest defenders of pharma.

  9. Doc,
    By all means lets empower the government to run even more of our lives. They do so well in the areas they already control.

  10. HC,
    Private industry is great, private pharma industry gone bad is not great. I’ve been in it too long and seen too much greed, so admitidly I’m biased.

  11. Doc,
    I aree that pharma has gone berserk…but I think the media plays up the missteps and makes us look worse than we are. I’d rather put checks and balances in place with private pharma than give government a major role in deciding which diseases do and do not merit funding…

    Look at the AIDS debacle…a disease which is 100% avoidable and we are throwing billions at it because of a vociferous political minority got the government involved. Malaria kills millions in Africa…but it is AIDS getting all the attention, when the AIDS “epidemic” in Africa could be halted with monogamy.

  12. Doc,

    We also need to overhaul the clinical trial process. The FDA’s requirements sometimes lead to useless data and restrictive PI information. The emphasis on placebo controls versus showing efficacy over established treatments is one area that needs to be addressed.

    Further–granting a guaranteed patent life after a drug is actually brought to market would allow the FDA to require studies showing actual clinical benefit. These studies often take years to perform, and companies have nothing to gain and much to lose by completing those studies before a product comes to market.

    As it is, a company develops its trials to give the FDA what it needs to approve the drug. People who actually know what they’re doing need to help revamp the structure of trials so that they actually provide useful information.

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