"Super HDL.." it will not work, sometimes.. the problem of increasing blood pressure is a no brainer one would think, but it might be more complex than that. Any sort of blood pressure increase, as evinced by recent tests on Pfizer's drug, one would think could be endothelial membrane de-stabilizing. You don't want the arterial plaque-walls getting shaky. Stable plaque with low BP is not that dangerous.
The Pfizer drug is far from "very dangerous". It caused an apparent increase in death, but that was from 52 deaths in the control group to 80 deaths in the Torcetrapib test group. Well that is a signficant increase, even given the test base of 15,000 persons, but there are many factors. The ones who died may have had a different kind of risk than other patients. Obviously they have to figure out what that risk is.
The other CETP inhibitors that block the change of HDL to LDL may not have the same problem as the Pfizer drug. Roche and Merck may not have the same problem. This is seen in the varying kind of statins. Some early kinds of statin like Bayclor were dangerous. Obviously Atorvastatin has a better record. It may not be time to throw in the towel on CETP drugs.
they just have to watch blood pressure more carefully, perhaps linking the drug to other supplements and amino complexes, calcium channel blockers, that may help to moderate the side effects of the drug. It may not be however that the BP alone was the problem. What cause the +BP might be much more insidious.
With deaths on their hands however, it is late to revisit that area.
This is too bad. This effect was not seen in phase one and two. It showed up late.
The nature of the resulting HDL particles created by the drug, although initial results seemed to show plaque reduction, may not be as helpful as was first thought.
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Pfizer Failure May Spur Delay on Roche, Merck Drugs
By Michelle Fay Cortez
Dec. 4 (Bloomberg) -- The failure of Pfizer Inc.'s experimental cholesterol drug may delay the drive for a new heart medicine by at least five years as Pfizer, Roche Holding AG and Merck & Co. sort out whether the treatment's risks carry over to similar cholesterol therapies.
Eighty-two patients taking the product, torcetrapib, with Pfizer's Lipitor died in a study of 15,000 enrollees, a 60 percent higher rate than among those who got only Lipitor. That caused Pfizer to halt work on the drug just days after the New York-based company said it would seek U.S. approval to sell torcetrapib in 2007. Roche and Merck are testing similar drugs.
Doctors have been searching for new ways to control heart disease, which kills about 650,000 Americans a year. Drugs such as Lipitor, called statins, lower bad cholesterol and cut risks of heart-related deaths by about a third. Scientists hoped that new medicines that raise good cholesterol, such as torcetrapib, would lower those risks further.
"We're going to keep attacking this," said Steven Nissen, chair of cardiology at the Cleveland Clinic in Ohio and president of the American College of Cardiology. "But here's the bad news - we're not going to have anything until 2010 or 2011 at the earliest given the failure of torcetrapib."
Pfizer, the world's biggest drugmaker, led Roche and Merck in the race to market a drug to raise good cholesterol, or HDL. Pfizer expected torcetrapib to replace revenue lost when Lipitor's patent protection ends in 2010, opening the way to generic competition. Pfizer has similar follow up products to Lipitor in early stage tests it may turn to now, analysts said.
Shares Plunge
Shares of Pfizer fell $2.96, or 10.6 percent, to $24.90 at 4:01 p.m. in New York Stock Exchange composite trading. They have gained 6.8 percent in 2006. Merck's shares rose 36 cents to $44.70. Basel-based Roche increased 30 centimes to 212.6 Swiss francs in Zurich.
"Suddenly you've really got a race," said Peter Cartwright, an Evolution Securities analyst in London. "Pfizer had been a lap ahead, but now it's a race again."
A U.S. Food and Drug Administration official said today that similar products to torcetrapib will now ``receive a little more scrutiny.
"We haven't seen any data yet," Steven Galson, director of the agency's Center for Drug Evaluation and Research, told reporters. "We really have to look at what caused this increase in mortality."
Lipitor
Lipitor, the world's best-selling drug, generates about $13 billion in annual revenue for Pfizer and accounts for about half of net income. Analysts have said they expected torcetrapib to eventually generate as much as $20 billion a year.
Doctors must now determine if the elevated risks stem from torcetrapib's tendency to boost blood pressure levels, or if the damage extends to the entire class of drugs. These drugs work by blocking the cholesterol ester transfer protein, or CETP, which converts good cholesterol, or HDL, into the bad form, or LDL.
"If it relates to blood pressure, we know of reports of other agents that are CETP inhibitors that don't have a blood pressure increase," said Chris Cannon, a cardiologist at Brigham and Women's Hospital in Boston. "It's still too early to know the cause of the increased mortality."
Whitehouse Station, New Jersey-based Merck refuses to talk about its CETP inhibitor, although it is widely discussed among investors, analysts and doctors.
Merck, Roche
Before the torcetrapib announcement, Merck had been expected to discuss details of its drug at a meeting later this month. Merck spokeswoman Janet Skidmore declined to comment after the Pfizer announcement came out.
Roche announced in 2004 it had licensed a CETP inhibitor from Tokyo-based Japan Tobacco Inc. Roche said its medicine hasn't increased blood pressure in trials, and is still expected to be submitted for approval after 2009.
"So far we have seen no blood pressure problems," said spokeswoman Katja Prowald in a telephone interview today. "Everything's going to plan. The regulatory filings are still planned for sometime after 2009."
While neither medication is tied to high blood pressure so far, doctors caution that torcetrapib's impact on blood pressure wasn't seen until phase 2 studies were complete. The side effect worsened during the third and final stage.
HDL, LDL
Doctors say HDL carries LDL away from the arteries and back to the liver, where it's passed from the body. LDL can slowly build up in the inner walls of the arteries that feed the heart and brain, blocking blood flow.
The worry is that the HDL created by blocking CETP is dysfunctional. The particles are larger than normal and may inadvertently add to plaque buildup, doctors said.
"The HDL particles created with this approach are so large and so structurally different that the HDL particles we think of as being protective may not be," said James Stein, director of preventive cardiology at the University of Wisconsin.
The results of a 1,190-patient study that's almost complete, being conducted by Nissen and his colleagues, may help doctors understand what happened. The trial used ultrasound to look at the impact of two years of torcetrapib plus Lipitor on the buildup of artery clogging plaque. Researchers are now analyzing results, Nissen said.
"If we look at the data and it shows the drug is increasing the buildup of plaque, then it may suggest the entire class" of CETP inhibitors "won't work," he said.
Regardless, investigators say they will continue to look for ways to increase levels of good cholesterol.
Abbott Laboratories agreed to buy Kos Pharmaceuticals Inc. for $3.7 billion last month to gain access to HDL-raising Niaspan. Studies show it helps remove some fatty plaque buildup on blood vessels walls that can cause heart attacks and strokes.
Niaspan, an extended release version of niacin, works differently than CETP inhibitors and carries other side effects, such as facial flushing.
To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net |
