The rationale of why the IMPROVE-IT will determine the extent of future layoffs

Discussion in 'Amgen' started by Anonymous, Nov 7, 2014 at 11:29 PM.

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  1. Anonymous

    Anonymous Guest

    Zetia and Vytorin are different ways of selling the same drug, ezetimibe, which blocks the absorption of cholesterol in the gut. Zetia is just ezetimibe, and lowers cholesterol 18%; Vytorin combines it with an older drug, a statin, with potent cholesterol-lowering ability for a one-two punch.

    In the study, called IMPROVE-IT, patients who had suffered heart attacks or chest pain were randomly assigned to either Vytorin or the statin, called simvastatin, alone. During the course of the trial, 34.7% of the patients who got only simvastatin had heart attacks, strokes, hospitalizations, or revascularization procedures, compared to 32.7% of those who got Vytorin. That 2% difference was statistically significant, and the difference was in heart attacks and strokes, not weaker measures like hospitalizations or stent procedures.


    1. The Result Is Modest

    The result is, in a word that came up regularly during interviews with 15 cardiologists and industry executives, “modest.” No deaths were prevented by using the $7-a-day Vytorin pill instead of a 25-cent generic.

    Researchers at Duke and Harvard’s Brigham & Women’s Hospital said in a press release that 50 patients had to be treated to prevent a heart attack or stroke – an impressive figure. But that’s over seven years. Over five years, the number would be 70, compared to 44 for other statin trials according study author Christopher Cannon. It would cost $880,000 to prevent that heart attack or stroke, at least until Zetia goes generic in 2016. “As expensive as it is, it’s less expensive than the cost of a stroke,” argues Duke University’s Robert Califf, one of the researchers who designed the study.


    To some cardiologists who have been critics of the drug, the size of the effect – a 6.4% relative decrease – remains an issue.

    “I will be the first to say it is a positive result, that it is a meaningful, it shows that lowering LDL with a non-statin, in this case ezetimibe, does in fact reduce morbidity and mortality a little bit,” says Steven Nissen of the Cleveland Clinic. “But it’s a very specific population, it is a very small population, and it took a very long time. It should not be overstated.”

    Allen Taylor, chief of the cardiology division at Medstar Georgetown University Hospital, was even stronger: “Risk reduction of 6% is nothing to dance around about,” he says. “It’s very clinically marginal. It’s positive only because it’s so big and so long they brought it down to such a low chance of failing that even a marginal clinical result like this could be statistically in the bounds of value.”

    2. This Could Still Mean A Boost In Sales For Merck

    To many practicing cardiologists and primary care physicians, all this is going to seem like angels dancing on the head of a pin. Vytorin was popular in part because it was so easy to give, and because some patients complain of aches and pains when they take statin drugs. Doctors stopped giving it because Merck appeared to try to bury a negative study that looked at whether Zetia prevented atherosclerosis. Now, with better data, they may feel justified in using the drug.

    “It’s not about the 6% difference,” says Lori Mosca, Director of Preventative Cardiology at New York Presbyterian University Medical Center. “It’s about the fact that I can use the combination drug and get low with no side effects.” The lack of a mortality benefit bothers her, she says, but preventing heart attacks and strokes can matter just as much.

    Primary care doctors are likely to re-embrace Zetia and the easy-to-understand idea that getting rid of cholesterol in the blood means a lower risk of heart attacks, says Howard Weintraub, director of the NYU Center For The Prevention Of Cardiovascular Disease. “Using Zetia is something I rely on, and I admit I did it with trepidation,” he says. “I’m sure ezetimibe will come back.”


    James Stein, director of the preventative cardiology program at the University of Wisconsin, Madison, sees many patients where he struggles to get their statin dose up high enough. “This study made my life a lot easier,” Stein says. “Now I can say let’s add some ezetimibe — like I used to.”

    Scripps Health Chief Academic Officer Eric Topol points out that just because a drug works in the very sick patients in this study doesn’t mean it should be used to try to prevent a first heart attack – where most statin prescribing happens. But things that shouldn’t happen frequently do. I think Merck could generate another $500 million in annual sales in 2015 because of this result. It won’t hurt that as the patent expiration nears, the company is likely to raise the drug’s price.

    3. This Is Scientifically Important

    One of the most important things about the study is that this is the first time that a new cholesterol-lowering drug has been added to a statin and been proved to further cut the rate of heart attacks and strokes. That is important evidence in a big scientific debate: whether statins cut heart attack rates through lowering the bad cholesterol, called low-density lipoprotein or LDL, or also through other effects.

    The verdict based on IMPROVE-IT: It’s the LDL, stupid.

    Patients who got only simvastatin, the generic statin, had LDLs of 70 milligrams per deciliter; those who got Vytorin had LDL’s of 63 mg/dL. “I think that is an important finding,” says Eugene Braunwald of Brigham & Woman’s Hospital, one of the most important cardiologists of the past century and a co-author of the study. “If we had taken patients who had failed statin therapy and showed ezetimibe was effective that would have been nice but not as important as this.”

    Because of all the controversy about Vytorin, 42% of the patients in the study stopped taking their medicine by the end of the trial. But this only seemed to weaken the results slightly; the 6% increase would have 7.6% based on a 17 point LDL difference.


    Not everyone is totally convinced. Krumholz notes that it’s still possible that something else about ezetimibe, not the LDL-lowering, is leading to the benefit. Sanjay Kaul of Cedars-Sinai Medical Center in Los Angeles says that given the amount of LDL-lowering in the trial, he would have expected a slightly bigger benefit — perhaps a 10% drop — in preventing heart attacks and strokes. In other words, it’s still possible that lowering cholesterol with Zetia works a little bit less better than lowering cholesterol with a statin.

    4. This Is Great News For Other Companies With Cholesterol Drugs

    If you’re developing another drug that cuts LDL cholesterol, this is great news. For one thing, the odds that your medicine will prevent heart attacks and strokes, too, just went up.

    That’s good news for Merck’s anacetrapib and Lilly’s evacetrapib, which are designed to boost high-density lipoprotein (HDL), the so-called “good cholesterol”, but which also cut LDL; similar medicines have failed. It’s better news for drugs that just reduce LDL cholesterol alone, like the new medicine being developed for Esperion Pharmaceuticals of Ann Arbor, Mich.

    But the biggest beneficiaries are the companies developing new injections that block a protein called PCSK9. These drugs reduce LDL dramatically, by as much as 50%, and are getting some patients to LDL levels as low as 25 mg/dL. The main competitors are Amgen and the team of Regeneron and Sanofi; their advertisements are all over the heart meeting, including on my room key. Pfizer and Eli Lilly also have PCSK9 drugs in development.

    For the leaders, this means it’s more likely the Food and Drug Administration will approve their drugs before big, IMPROVE-IT like studies are completed. (Unlike Merck, which took years to start IMPROVE-IT, now companies are required to have the studies up and running before approval can happen.) The FDA says it needs time to examine the IMPROVE-IT results; Merck will be filing them with the agency in order to try and get a new marketing claim.


    Another advantage, though, could come not from regulators but from doctors, who will now have a stronger belief in LDL. If the drugs are approved, this could speed their adoption.

    “There were lots of doubts that anybody would pick up a cholesterol drug before they had really strong outcome data,” says Elia Zerhouni, the head of R&D at Sanofi. “That’s what IMPROVE-IT does for us. It will basically say this is a revolutionary option that will be established in the medical world faster than I thought it would.”
     

  2. Anonymous

    Anonymous Guest

    I am just glad to read one post that is objective regarding the outlook for Evo. Should be a great product for Amgen. Now we just need to launch it right.
     
  3. Anonymous

    Anonymous Guest

    Before gets approved everyone including FDA should be aware of the poor manufacturing practices There doing in ATO ..
     
  4. Anonymous

    Anonymous Guest

    Could you define what "launch it right" means?
     
  5. Anonymous

    Anonymous Guest

    A launch not done by Amgen
     
  6. Anonymous

    Anonymous Guest

    Amazing how the outcomes of the study are considered by the street as favorable for Evo and yet our own people from other BUs still feel the need to hate and make cracks on their own company.
    This site is really a joke. Most losers just here to bash on other people/BUs with half truths and info gathered from employees that are so disgruntled they should have left a long time ago.

    Evo will be great for Amgen and the new BU is a great place to be.
     
  7. Anonymous

    Anonymous Guest

    Let's hope you are accurate. Our collective future is riding on it.