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Tuesday, July 31, 2007

Here's What's Up

The people's hero, David Graham, MD, a drug safety officer at the F.D.A., called for Avandia’s withdrawal. Dr. Graham estimated that its toxic effects on the heart had caused as many as 205,000 heart attacks, strokes and death from 1999 to 2006. For every month that Avandia is sold, he said, another 1,600 to 2,200 patients are likely to suffer from heart attacks and strokes, some of them fatal.

Meanwhile, back at 'the ranch'- depending on whether you define this as the Oval Office which benefits from millions in Pharma Cartel money, the new 'faster track' fast-track drug approval for money scheme, thousands paid in lobbying efforts to senators and representatives to pass the recent drug bill originally brought to you by Teddy Kennedy, or the failure to pass a Medicare drug bill allowing price negotiation (a Bush giveaway) - the people have been had. Especially any one with diabetes.

We reported over four years ago to all the people with diabetes on our news service alert plan the cardiac risks of Avandia. Readers of our most recent newsletter learned more.

This is not unlike how more than fifteen years ago we began warning women NOT to submit to mammography because it DOES cause cancer. Today you read this same news again because someone did a new study. yet when do you see that there has been a change to thermography or ultrasound for diagnosis in all these years. You don't. And you don't because of the $$$.

We agree with Dr. Graham. In the mean time, so should you.

We also agree that everyone should force this issue with their elected officials, especially if they are ones who voted for this FDA bill (see a recent post about being screwed by Congress). And we strongly agree that there should be NO drug on the market with any serious health risk as a side effect. For the FDA, to do less is unconscionable.

Read here about drugs: (skip the patient information, because that's just fluff).

And if you want to know healthful and safe approaches to prevent and care for diabetes, let us know. The VA has proven it is reversible, so the facts are in.

There is help for Type I too.

Advisers: Avandia should stay on market

By ANDREW BRIDGES, Associated Press Writer Mon Jul 30, 6:41 PM ET

The widely used diabetes drug Avandia should remain on the market, government health advisers overwhelmingly recommended Monday, saying evidence of an increased risk of heart attack doesn't merit removal.

The nonbinding recommendation to the Food and Drug Administration came on a 22-1 vote by the panel.

"We're being asked today to take a very draconian action based on studies that have very significant weaknesses and are inadequate for us to make that kind of decision," said Rebecca Killion, a diabetic from Bowie, Md., and the panel's patient representative.

However, in an earlier 20-3 vote, the panelists said that available data show the drug does increase heart risks.

Panelists said the drug's label should include a so-called "black-box" warning, the most severe the FDA can require, to flag that risk. Some suggested the label caution against using the drug together with insulin because doing so may elevate heart risks. That joint use is currently FDA-approved. The experts also asked that the drug be studied further.

The FDA isn't required to follow the advice of its advisory committees but usually does.

The manufacturer, GlaxoSmithKline PLC, earlier recommended continuing long-term studies of the drug and updating the label to inform doctors and patients of what's known so far about any heart risks. FDA scientist Dr. David Graham said waiting for more results could subject as many as 2,200 people a month to serious side effects from the drug.

Graham also told the joint panel of experts that the drug's heart risks, combined with its lack of unique short-term benefits in helping diabetics control blood sugar, meant continued sales were not justified.

But Glaxo contended there is no increased risk, citing its own analyses of studies of Avandia, also called rosiglitazone.

"The number of myocardial infarctions is small, the data are inconsistent and there is no overall evidence rosiglitazone is different from any other oral antidiabetes agents," said Dr. Ronald Krall, the company's senior vice president and chief medical officer.

Previously, the FDA had said information from dozens of studies pointed to an increased risk of heart attack.

That conclusion swayed the panel but apparently did not rise to the level of requiring any regulatory action more dire than beefed-up warnings and continued scrutiny.

"It's suggestive but by no means conclusive," said Dr. Thomas Pickering, an assistant professor of medicine at Columbia University Medical Center.

The lone dissenting panel member on the main vote, Arthur Levin, said there was a strong suggestion of a safety signal. That, along with widely shared doubts that further study would settle the issue and the enormity of the potential risk to the public health, moved him to vote "no."

"I logically can't find any way to leave this drug on the market," said Levin, director of the Center for Medical Consumers in New York.

About 1 million Americans with Type 2 diabetes use Avandia to control blood sugar by increasing the body's sensitivity to insulin. That sort of treatment has long been presumed to lessen the heart risks already associated with the disease, which is linked to obesity. News that Avandia might actually increase those risks would represent a "serious limitation" of the drug's benefit, according to the FDA.

Graham's boss, Dr. Gerald Dal Pan, also said the balance between the risks and benefits of Avandia didn't favor the drug. But the FDA isn't of one mind on the drug: the issue exposed a rift between agency officials charged with approving new medicines and those who monitor their safety once on the market.

"It is important that the committee understand there is a fundamental disagreement within (the FDA's drugs office) on the scientific conclusions that should be drawn," said Dr. Robert Meyer, head of the FDA office that reviews new diabetes drugs.

The FDA moved up the date of Monday's meeting after the May publication of a study in The New England Journal of Medicine that generated new concerns about Avandia's safety. The analysis of 42 studies revealed a 43 percent higher risk of heart attack for those taking Avandia compared with people taking other diabetes drugs or no diabetes medication.

Separately, the FDA is working to add so-called "black box" warnings to the labels of both Avandia and a second oral diabetes drug, Actos, to caution patients about the increased risk of heart failure associated with the drugs. That risk is separate from those discussed Monday.

The diabetes epidemic affects more than 18 million Americans. Most have Type 2, where the body makes too little insulin or cannot use what it does produce.

Each day, there are 4,100 new cases of diabetes in the United States, and 810 deaths, said Dr. Robert Ratner, vice president of medical affairs at the MedStar Research Institute. Of those deaths, 60 percent are due to heart disease, Ratner told the panel.

Congress has pointed to Avandia as evidence of FDA's fumbling of safety problems that emerge long after drugs win agency approval. The House and Senate are at work on legislation to overhaul the FDA.

On the Net:
Food and Drug Administration:

July 30, 2007
F.D.A. Panel Votes to Keep Diabetes Drug on Market

GAITHERSBURG, Md., July 30 — A federal drug advisory committee voted 20 to 3 late this afternoon that Avandia, a controversial diabetes drug made by GlaxoSmithKline, raises the risks of heart attacks, but it then voted 22 to 1 that the drug should nonetheless remain on the market.

The divided vote came after committee members said that studies concerning Avandia were too murky to merit drastic regulatory action and that other diabetes medicines might have similar risks.

“My feeling here is that we’re being asked to take a very draconian action based on studies that are very inadequate for us to make that kind of decision,” said Rebecca Killion, a patient representative and committee member from Bowie, Md.

Dr. Clifford J. Rosen, chairman of the committee who is from St. Joseph Hospital in Bangor, Me., said after the meeting that “there was enough concern on the advisory committee that virtually everybody felt there was risk” of heart attacks from taking Avandia.

Patients who have congestive heart failure or a history of cardiovascular disease, or those taking insulin or nitrates should not be given Avandia, Dr. Rosen said.

“There are going to be changes in the way this is promoted and certainly in how physicians use this drug,” Dr. Rosen predicted.

GlaxoSmithKline told the committee that it did not believe that Avandia increases the risks of heart attacks “and we still don’t,” said Christopher A. Viehbacher, president of the company’s American drug business, after the meeting ended.

He said that if the F.D.A. ordered a strong warning placed on Avandia’s label, some patients would take other medicines that might be more dangerous. “I don’t think it’s a slam dunk yet as to what the F.D.A. is going to do with this,” he said.

The votes came after an extraordinary meeting in which officials from the Food and Drug Administration, which brought the committee together, openly disagreed with one another about the right course to take.

Dr. David Graham, a drug safety officer at the F.D.A., called for the drug’s withdrawal and estimated that its toxic effects on the heart had caused as many as 205,000 heart attacks, strokes and death from 1999 to 2006. For every month that Avandia is sold, he said, another 1,600 to 2,200 patients are likely to suffer from heart attacks and strokes, some of them fatal.

Dr. Robert Meyer, director of the office within the F.D.A. that approved Avandia’s initial application, immediately disagreed with Dr. Graham.

“I think it’s important that the committee understand there’s a fundamental disagreement” within the agency, he said. Other diabetes drugs also have risks, Dr. Meyer said, and doctors and patients need a variety of treatment options.

Dr. Douglas C. Throckmorton, a deputy director of the F.D.A.’s center for drugs, explained at a news conference after the meeting that the split within the agency resulted from the “complexity” of the issue.

The F.D.A. usually follows the advice of its advisory committees, especially when the votes are so lopsided. Agency officials said they did not know when they would come to a decision and refused to characterize the form that any new Avandia warning might take.

The open disagreement within the F.D.A. reflects a fierce debate that has occurred among diabetes experts across the country since The New England Journal of Medicine published a study in May suggesting that Avandia increases the risks of heart attacks.

In the revelations since then, F.D.A. officials have said that GlaxoSmithKline told the agency about these risks nearly two years ago, but that because of fierce internal disagreements, the agency never warned patients about them. In Europe, regulators required that the drug’s label reflect some concerns about these risks.

The agency’s lack of action helped persuade some lawmakers to support legislation that has since passed both the House and Senate that provides the agency with more money and power to police drug safety issues. That legislation is expected to be sent to President Bush within days.

About a million patients in the United States took Avandia last year, and a nearly identical number took Actos, a similar pill made by Takeda that may be safer. Avandia’s global sales last year totaled $3.4 billion, but its sales have plunged since May.

The Avandia controversy largely revolves around whether several highly complex statistical analyses of dozens of studies show that Avandia increases the risks of heart attacks. Separate from this argument, there is considerable evidence that both Avandia and Actos worsen the condition of heart failure.

Dr. Murray Stewart, a GlaxoSmithKline vice president, said that in recent months the company has examined data from several large managed care companies in the United States that included 1.35 million patients with diabetes. The company’s analyses, he said, showed that patients who took Avandia suffered no greater risk of heart attack or death from heart problems.

The committee disagreed, with most members saying that while GlaxoSmithKline should continue to market Avandia, the F.D.A. should place strict warnings on its label.

“I also think there needs to be a stiffening of the warnings,” said Dr. Peter J. Savage, a committee member from the National Institutes of Health, echoing the comments of others.

Dr. Steven Nissen, a Cleveland Clinic cardiologist who authored the study in The New England Journal of Medicine in May, said in an interview after the hearing that he would have voted to remove Avandia from the market. But he said he was encouraged that the committee “affirmed the finding that there was an increased cardiovascular risk from the drug.”

He predicted that Avandia’s sales would plunge with the new warning.

The disagreements within the F.D.A. affected almost every aspect of the hearing. In their presentations, Dr. Graham and his boss, Dr. Gerald Dal Pan, both referred to studies that suggested that Actos is safer to the heart than Avandia. But the Actos studies have not been thoroughly reviewed by the F.D.A., and the underlying data from them were not given to committee members.

When asked why, Dr. Graham said that “we were promised that that would be done for this meeting.” Officials eventually explained that the agency did not enough resources to get the analysis done for the meeting, he said.

“So then I’m faced with a dilemma,” Dr. Graham said. “Do I keep silent about that and not breathe a word of it, or do I present it?”

Dr. John R. Teerlink, a committee member from the University of California in San Francisco, said that the agency should “either have the political will to either schedule the meeting when we had the data or not to present data that we couldn’t look at.”

The public debate about Avandia has brought about a remarkable number of independent examinations of the drug’s safety, and several researchers shared their findings with the committee during the hearing’s open public comment period.

Executives with both Tricare, a managed care company that serves active and retired military personnel, and WellPoint, a huge health insurer, said they had found no evidence in their records that patients given Avandia had suffered more heart attacks.

Dr. Sidney Wolfe of the drug safety advocacy group Public Citizen, said F.D.A. records show that Avandia has a lot more problems associated with it than just heart risks.

“If Avandia were up for approval today, based on what we know now, it would be rejected,” he said.

Multiple speakers reminded the committee that few diseases have a greater public health impact than diabetes. Each day in the United States, there are 4,100 new diabetes cases and 810 deaths from the disease, said Dr. Robert E. Ratner of the MedStar Research Institute in Washington. Also every day, about 230 diabetes patients suffer amputations, 120 suffer kidney failure and 55 go blind.

He said that while controlling blood sugar levels has proven health benefits in the short term, no study has proven that diabetes drugs extend lives.

“We’re not keeping people alive with our drug therapy because our drug therapy isn’t adequate,” he said. And he said that no diabetes medicine has conclusively proven that it helps protect the heart. He also noted that diabetes patients often fail to take their medicines properly, and that doctors often fail to treat the disease aggressively enough.

“Why do we need new therapies for type-two diabetes?” Dr. Ratner asked. “We have an epidemic of diabetes and its complication that will soon swamp our medical delivery system.”

Most diabetics die from heart disease, since the disease has severe effects on the heart. If Avandia actually increases the risks of heart attacks, that “denotes a serious limitation” of the drug’s usefulness, an F.D.A. reviewer concluded in a report before the meeting.

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