Avandia / Rosiglitazone "worst drug safety catastrophe certainly in our lifetimes" ...

Avandia / Rosiglitazone "worst drug safety catastrophe certainly in our lifetimes" ...

Joined: April 19th, 2005, 7:01 pm

July 13th, 2010, 10:18 am #1


http://www.cbsnews.com/stories/2010/07/12/eveningnews/main6671811.shtml
Diabetes Drug to Get Second LookFDA to Decide Whether to Pull Avandia From the Market
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Joined: April 19th, 2005, 7:01 pm

July 13th, 2010, 10:21 am #2


http://www.nytimes.com/2010/07/13/health/policy/13avandia.html

<strong>Diabetes Drug Maker Hid Test Data on Risks, Files Indicate</strong>
By GARDINER HARRISPublished: July 12, 2010<div class="articleTools"><div class="box"></div></div><div class="articleBody">
Avandias success was crucial to SmithKline, whose labs were otherwise all but barren of new products. But the studys results, completed that same year, were disastrous. Not only was Avandia no better than Actos, but the study also provided clear signs that it was riskier to the heart.

But instead of publishing the results, the company spent the next 11 years trying to cover them up, according to documents recently obtained by The New York Times. The company did not post the results on its Web site or submit them to federal drug regulators, as is required in most cases by law.

This was done for the U.S. business, way under the radar, Dr. Martin I. Freed, a SmithKline executive, wrote in an e-mail message dated March 29, 2001, about the study results that was obtained by The Times. Per Sr. Mgmt request, these data should not see the light of day to anyone outside of GSK, the corporate successor to SmithKline.

The heart risks from Avandia first became public in May 2007, with a study from a cardiologist at the Cleveland Clinic who used data the company was forced by a lawsuit to post on its own Web site. In the ensuing months, GlaxoSmithKline officials conceded that they had known of the drugs potential heart attack risks since at least 2005.

But the latest documents demonstrate that the company had data hinting at Avandias extensive heart problems almost as soon as the drug was introduced in 1999, and sought intensively to keep those risks from becoming public. In one document, the company sought to quantify the lost sales that would result if Avandias cardiovascular safety risk intensifies. The cost: $600 million from 2002 to 2004 alone, the document stated.

Mary Anne Rhyne, a GlaxoSmithKline spokeswoman, said that the company had not provided the results of its study because they did not contribute any significant new information.

The company said that Avandia was safe and that Dr. Freed no longer worked for GlaxoSmithKline.

A panel of experts will meet Tuesday and Wednesday to decide whether Avandia should still be sold and whether it is ethical to test Avandia directly against Actos.

Whether to withdraw Avandia is a question that has split the F.D.A., with some officials arguing that the drug is useful despite its risks and others insisting that it must be withdrawn.

According to the documents, Dr. John Jenkins, director of the agencys office of new drugs, who has argued internally that Avandia should remain on the market, briefed the company extensively on the agencys internal debate.

It is clear the office of new drugs is trying to find minimal language that will satisfy the office of drug safety, a top company official wrote in an e-mail message after he spoke with Dr. Jenkins, according to a sealed deposition obtained by The Times.

In the deposition, Dr. Rosemary Johann-Liang, a former supervisor in the drug safety office who left the F.D.A. after she was disciplined for recommending that Avandias heart warnings be strengthened, said of Dr. Jenkins conversations with GlaxoSmithKline, This should not happen, and the fact that these kind of things happen, I mean, I think people have to make a determination about the leadership at the F.D.A.

An F.D.A. spokeswoman said the agency would not comment on the contents of the deposition.

Members of Congress, where the Avandia case has led to legislative changes, said they were outraged at GlaxoSmithKlines behavior.

When drug companies withhold data regarding safety concerns about their medicines, they put patients at risk, said Senator Max Baucus, Democrat of Montana, who is chairman of the Senate Finance Committee. Mr. Baucus and Senator Charles E. Grassley of Iowa, the committees ranking Republican, spent years investigating GlaxoSmithKlines development of Avandia.

Besides the trial comparing Avandia with Actos, the company also conducted trials comparing Avandia with glyburide, a cheaper and older diabetes medicine.

When Rhona A. Berry, a company official, asked about publishing two of the trials, Dr. Freed responded in an e-mail message dated July 20, 2001, that referred to Avandia by the abbreviation of its generic name, rosiglitazone: Rhona Not a chance. These put Avandia in quite a negative light when folks look at the response of the RSG monotherapy arm, the message said. It is a difficult story to tell and we would hope that these do not see the light of day.

Hiding the results of negative clinical trials was once widespread in the drug industry.

But after GlaxoSmithKline was found in 2004 to have hidden data that showed that its antidepressant, Paxil, led children and teenagers to have more suicidal thoughts and behaviors, the company settled a lawsuit by agreeing to publicly post data from all of its trials. In 2007, Congress mandated such disclosures. But the postings are often little more than cryptic references, so the issue is far from resolved.

With Avandia, GlaxoSmithKline has done more than hide trial data. An F.D.A. reviewer who closely examined a landmark Avandia clinical trial called Record, found at least a dozen instances in which patients taking Avandia suffered serious heart problems that were not counted in the trials tally of adverse events, mistakes that further obscured Avandias heart risks.

The companys conduct of the Record trial has received sharp criticism from medical leaders for other reasons as well. To compare Avandia and Actos in 1999, researchers at SmithKline measured Actoss effects in patients in the same way that they had conducted earlier trials of Avandia so that the results for the two drugs could be compared.

When the results of the study suggested that Avandia was more dangerous than Actos, the company decided against further comparisons.
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Last edited by SSRIAdmin on July 13th, 2010, 10:26 am, edited 1 time in total.
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Joined: April 19th, 2005, 7:01 pm

July 13th, 2010, 10:25 am #3


http://www.guardian.co.uk/business/cartoon/2010/jul/13/kipper-williams-glaxosmithkline-avandia-fda
GlaxoSmithKline Avandia FDA
Glaxo on red alert as FDA scrutinises diabetes drug Avandia

guardian.co.uk, Tuesday 13 July 2010 08.33 BST
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Joined: April 19th, 2005, 7:01 pm

July 14th, 2010, 8:48 am #4

http://www.cbsnews.com/stories/2010/07/12/eveningnews/main6671811.shtml
Diabetes Drug to Get Second LookFDA to Decide Whether to Pull Avandia From the Market
http://www.foxnews.com/story/0,2933,596622,00.html?mep
"Avandia Hearings to Reveal True Dangers of Popular Drug
Tuesday, July 13, 2010 <img alt="" src="http://www.foxnews.com/images/foxnews_story.gif">
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<strong>Risks from Avandia are great enough to "put you in a hospital or in a cemetery. Thats a direct quote from Dr. David Graham, the lead author of a study, that ultimately led the Food and Drug Administration to hold a hearing on the safety of the popular diabetes drug.</strong>

On June 28, the study was released connecting the controversial drug to a higher risk of heart problems, strokes and deaths in older adults, and said it was more dangerous than a rival drug, Actos.

Graham said the study, which was a huge review of Medicare records, warrants enough information for the pill to be banned and pointed out that 100,000 heart attacks, strokes, deaths and cases of heart failure may be due to Avandia since it came on the market in 1999.

"The evidence is overwhelming," Graham said. "There is not a single study where those two drugs are compared where Avandia doesn't look worse than Actos. How many studies do you have to do before you come to your senses?"

Avandia's maker, the British company GlaxoSmithKline PLC, maintains that its drug is safe. A spokeswoman said the new study has limitations, and that the company looks forward to a full discussion of evidence at the FDA hearing.

This is not the first time Avandia has been under suspicion. In May 2007, when a review of dozens of studies suggested it may raise the risk of heart-related deaths, warnings were added to its label.

In response to the trials, the American Heart Association issued a statement reminding patients not to stop taking any medicine without talking with their doctors first. The new study is not definitive enough to prove harm, but "deserves serious consideration" and should be discussed between patients and their doctors.

Avandia is a once-blockbuster drug for Type 2 diabetes, the most common form of the disease and the kind often tied to obesity. Avandia and Actos are both pills that help the body make better use of insulin, a key digestive hormone.

The study by the FDA that put GlaxoSmithKilne under fire involved 227,571 Medicare patients, average age 74, who started on Actos or Avandia from July 2006 through June 2009 and were followed for three years on average.

<strong>Avandia patients were 27 percent more likely to suffer strokes, 25 percent more likely to develop heart failure and 14 percent more likely to die than those on Actos, researchers found</strong>.

There were 2,593 heart attacks, heart failure cases, strokes and deaths among the 67,593 Avandia users, and 5,386 of those problems among the 159,978 people taking Actos. Just dividing these numbers to compare side effect rates can't be done, though, because people were on the drugs for differing lengths of time.

The findings suggest that if 60 people were treated with Avandia for one year, one extra case of heart failure, stroke or death would occur that could have been avoided if they'd taken Actos instead, Graham said.

At its hearing Tuesday, the FDA plans to examine the latest safety data and air internal disagreement among its scientists over what should be done.

Options regulators can consider include adding more warning labels, limit which doctors can prescribe Avandia or pull it from the market completely.

<em>The Associated Press contributed to this article."</em>
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July 16th, 2010, 6:43 pm #5

http://www.cbsnews.com/stories/2010/07/12/eveningnews/main6671811.shtml
Diabetes Drug to Get Second LookFDA to Decide Whether to Pull Avandia From the Market
which is what we expect from the FDA on decisions re dodgy medications....

http://www.telegraph.co.uk/finance/newsbysector/epic/gsk/7892866/GlaxoSmithKline-1.6bn-legal-charge-to-hit-earnings.html
<div class="storyHead">GlaxoSmithKline £1.6bn legal charge to hit earnings GlaxoSmithKline investors who breathed a sigh of relief after learning that the drugmaker's diabetes pill, Avandia, had won a reprieve from advisers to America's medicines watchdog, might have been forgiven for taking a sharp intake of breath yesterday. </div><div class="oneHalf gutter"><div class="story"><div class="byline">
By Rachel Cooper, City Reporter, Pharma
Published: 6:45AM BST 16 Jul 2010
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<strong>GlaxoSmithKline</strong>
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Just hours after an advisory panel to the Food and Drug Administration voted that Avandia was safe enough to stay on sale <strong>despite concerns about possible risks to the heart</strong>, Britain's biggest drugmaker revealed that it will book a £1.57bn charge in the second quarter to settle a range of long-standing legal cases. The figure is in addition to an existing £2.3bn of provisions and includes settlements, agreements to settle and provisioning for cases dating back to the 1990s.
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The charge will be £1.35bn after tax and analysts expect that it will slash second-quarter earnings-per-share by more than 26p, wiping out most of the group's profit for the period, but will provide more clarity going forward.
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Dan Troy, general counsel at GSK, said it represented a "susbstantial proportion" of the company's outstanding litigation. He added that the charge reflected the company's ongoing efforts to resolve long-standing legal cases and the progress was helping the drugmaker to reduce financial uncertainty and risk for shareholders.

The news comes towards the end of a difficult week for GSK, during which it has been fighting to defend Avandia from claims that it can pose an increased risk of heart problems.

Having spent two days listening to evidence on the safety of Avandia, an expert panel on Wednesday voted to keep it on the market, but with increased restrictions or warnings. The FDA is not obliged to follow the advice of its panels, but often does.

Analysts said they saw the announcement of the legal charge so soon after the Avandia vote as a "clearing of the decks" on GSK's part after a period of uncertainty.

Mark Clark, an analyst at Deutsche Bank, said: "They already had these settlements lined up, they could have waited until second-quarter results, but given the Avandia vote, they thought they could use it as an overally tidying up exercise."

"I would characterise this news as positive because this year, the weakness in the stock has been due to investors sitting on sidelines because of unquantifiable fears about litigation," he added, saying that people could now view the stock on a proper ongoing basis again.

GSK's shares closed up 21½ at £12.03 suggesting that on balance, investors were feeling more upbeat.

Amongst the outstanding litigation is the settlement of the "substantial majority" of product liability cases relating to Avandia. Earlier this week, it was reported that GSK had settled around 10,000 of an estimated 13,000 cases for $460m, which was significantly less than some analysts had been expecting.

There had been fears GSK might have to spend as much as $6bn to resolve the claims, but in light of the favourable panel vote and reports of modest settlements, some analysts now think the bill could be $1bn or less.

GSK also said it had now fully resolved anti-trust litigation and settled the "vast majority" of product liability cases relating to its anti-depressant, Paxil. GSK has received numerous lawsuits and claims alleging that the use of Paxil has caused a variety of injuries, according to its annual report.

Many of these suits allege that the use of Paxil during pregnancy resulted in the birth of a child with birth defects or health issues. Others allege that patients who took Paxil committed or attempted to commit suicide and/or acts of violence.

GSK added yesterday that it had provisionally agreed to pay £500m to settle a probe by the US government into alleged manufacturing problems at a former plant in Cidra, Puerto Rico. "
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Joined: April 19th, 2005, 7:01 pm

July 20th, 2010, 6:43 pm #6

http://www.cbsnews.com/stories/2010/07/12/eveningnews/main6671811.shtml
Diabetes Drug to Get Second LookFDA to Decide Whether to Pull Avandia From the Market
http://www.aboutlawsuits.com/fda-avandia-panel-member-conflict-uncovered-11568/
FDA Avandia Panel Member Found to Have Received Fees from Drug Maker<div class="postinfo"><div></font> </div>
Published: July 20th, 2010 <font color="#003366">No Comments

</div><div class="entry"><img alt="feature photo" src="http://www.aboutlawsuits.com/wp-content/uploads/fda-220.gif">
Concerns have been raised that a member of the FDA Advisory Panel that recently voted that the <strong>diabetes drug Avandia should not be recalled</strong> may have failed to disclose that he was a paid speaker for GlaxoSmithKline, the drugs maker. <span></span>

Endocrinologist David Capuzzi was <strong>one of only three members out of a 32-member panel who voted that nothing further needed to be done to warn the public about </strong><strong>side effects of Avandia</strong><strong>.</strong> The majority of the panel voted that the diabetes drug, which has been linked to heart attack risk, should receive more stringent label warnings or should be restricted in use; 12 members of the committee voted in favor of an <strong>Avandia recall</strong>.

According to an article published in the <strong>Wall Street Journal</strong>, Capuzzi received $3,750 from GlaxoSmithKline for speaking engagements from April 2009 through March 2010. Before that, he was paid $8,000 for speaking on the companys behalf, and since March hes received about another $3,000. However, the committee appeared to be unaware of the connection last week.

Capuzzi has said he told the FDA about the payments. The agency has announced that it is looking into whether full disclosure was made and why the committee was not informed.

The FDA approved Avandia (rosiglitazone) in 1998 to treat type 2 diabetes by helping control blood sugar levels. The drug has been used by millions of diabetics, but sales have plummeted in recent years as concerns have mounted about the risk of serious and potentially life-threatening <strong>heart risks with Avandia</strong>.

<strong>Avandia</strong> has come under harsh criticism in recent months by a number of experts, including some FDA drug safety reviewers, who have estimated that Avandia may be responsible for more than 100,000 heart attacks and deaths since it was approved. Critics have argued that Avandia should be recalled, as there is no reason to put patients at risk with the drug when there are alternative treatments that do not appear to carry the same heart attack risk as Avandia.

The FDA is conducting an ongoing safety review of Avandia, and is expected to make a decision about what they will do with the medication in the near future. Although the FDA is not required to follow the recommendations of their advisory committees, they often do. The federal regulatory agency has also previously indicated that they are considering shutting down an on-going clinical trial involving Avandia, as many have indicated it is unethical to continue due to the know risk of life-threatening injuries from Avandia side effects.

In a highly-anticipated committee hearing last week, which included Capuzzi, an FDA advisory committee voted 20-12 to allow Avandia to stay on the market, although 17 members said it should only do so with further restrictions and warnings. Three, including Capuzzi, said Avandia needed no new warnings.

Capuzzi said that despite his vote, he does not recommend the use of Avandia or any similar products to his patients, instead relying on older metaformin-based diabetes drugs for patients.

The controversy of the disclosure comes as a group of doctors announced this week that they are suing the FDA over Avandia problems. The lawsuit was filed by the nonprofit Physicians Committee for Responsible Medicine (PCRM) in the U.S. District Court for the District of Columbia. The doctors group is attempting to use the lawsuit to force FDA to place information on the Avandia label alerting consumers to the fact that there are dietary alternatives to drugs like Avandia.

The lawsuit claims that FDA Commission Margaret Hamburg failed to act on a petition to make the label changes. The labeling petition calls for FDA to add a label to Avandia and similar drugs saying that low fat, plant-based diets are as or more effective and safe than oral diabetes medications.

Earlier this month, GlaxoSmithKline reportedly agreed to <strong>settle Avandia lawsuits</strong> filed by about 10,000 out of an estimated 13,000 people who claim that they or family members suffered injuries as a result of the drug makers failure to warn about the risk of Avandia heart attacks.
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Joined: April 19th, 2005, 7:01 pm

July 20th, 2010, 6:49 pm #7


"...Endocrinologist David Capuzzi was <strong>one of only three members out of a 32-member panel who voted that nothing further needed to be done to warn the public about </strong><strong>side effects of Avandia</strong><strong>.</strong>

 

The <strong>majority of the panel </strong>voted that the diabetes drug, which has been linked to heart attack risk, <strong>should receive more stringent label warnings or should be restricted in use; 12 members of the committee voted in favor of an </strong><strong>Avandia recall</strong>..."

 

 
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Joined: April 19th, 2005, 7:01 pm

July 22nd, 2010, 4:55 pm #8

http://www.cbsnews.com/stories/2010/07/12/eveningnews/main6671811.shtml
Diabetes Drug to Get Second LookFDA to Decide Whether to Pull Avandia From the Market
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