But don’t expect physicians to write as many prescriptions for the Type 2 diabetes drug as they have in the past. Avandia brought in $1 billion in sales last year with more than 2 million prescriptions filled. But studies showing heart attacks, strokes and cardiovascular-related deaths in people who used Avandia have prompted national experts in a Consensus Statement of the American Diabetes Association to unanimously advise that GlaxoSmithKline’s blockbuster medication not be used.

While Avandia will still be available, the FDA vote showed a strong majority – 21 out of 33 members – believe Avandia increases heart risk. Twelve out of 33 members voted to take it off the market, and 10 out of 33 voted to leave it on with strong restrictions.

And while the FDA advisory panel heard damning evidence on the safety of Avandia, it was reported that GSK had agreed to settle some 10,000 of the 13,000 lawsuits filed against it alleging that Avandia caused heart attacks or strokes.

What diabetics should glean from the vote is that they need to be aware that there is a dark cloud of suspicion hanging over the safety of Avandia, which should be enough evidence for them to consider the many safer alternatives on the market.

SOURCE: Avandia Recall › Dark cloud hangs over Avandia despite FDA vote to keep it on market

Avandia was approved by the Food and Drug Administration (FDA) in 1999 to treat Type 2 diabetes, the fastest growing form of diabetes. GSK launched a multimillion-dollar ad campaign to introduce the drug to the market, which brought in $1 billion in sales last year alone with more than 2 million prescriptions filled.

A 2007 study found that Avandia could increase the risk of heart attack by as much as 43 percent, and more recent studies suggest that Avandia may be responsible for thousands of cardiovascular events such as heart attacks, strokes and other heart problems. In 2007, an FDA panel reviewed the data but voted not to pull the drug off the market.

However, concerns over a new study on the drug has led the FDA to conduct a second review the safety of Avandia. The agency is also questioning whether GSK tried to cover up the risks associated with the drug.

The panel is expected to vote soon on whether to remove the popular diabetes drug from the market.

SOURCE: Avandia Recall › GSK to pay $460 million to settle Avandia lawsuits

Avandia, also known by the generic name rosiglitazone, faced the same panel in 2007, which voted 22-1 to keep the drug on the market despite a separate vote of 20-3 that there probably was a link to heart problems. Since then, several publications have come out both in support of and against the safety of Avandia. One major topic of this second go-round with the panel includes an analysis of the RECORD study, which the Food and Drug Administration’s Dr. Thomas Marciniak of the division of cardiovascular and renal products wrote, “was inadequately designed and conducted to provide any reassurance about the (cardiovascular) safety of rosiglitazone.”

The 5 ½-year RECORD study involved nearly 5,000 diabetes patients and showed that the drug was not related to an increase in cardiovascular events other than congestive heart failure, which is a documented side effect of drugs used to treat diabetes.

Avandia is a blockbuster medication approved in 1999 to treat Type 2 diabetes, the most common form of the disease. More than a million people in the U.S. have taken the drug. Studies have concluded that Avandia raised the risk of heart attacks in people who used the drug by as much as 43 percent compared to people taking no diabetes medication or other diabetes drugs. Studies have also indicated that Avandia might increase the risk of heart-related deaths.

However, GSK backs the RECORD study, which the FDA argues is “inappropriate and biased.” The panel is expected to vote soon whether to pull the popular diabetes drug off the market.

SOURCE: Avandia Recall › FDA panel to decide fate of diabetes drug Avandia

According to the FDA’s announcement, the “FDA previously communicated to the public about the possible association between rosiglitazone and increased cardiovascular risk in a 2007 safety alert. The agency also sought advice from external experts at the July 30, 2007, joint meeting of the FDA Endocrinologic and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees. The RECORD study data represent the only new information from a completed randomized, controlled clinical trial of rosiglitazone received by FDA since the 2007 announcements.”

The RECORD study, which stands for Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes, was designed to evaluate the cardiovascular safety of rosiglitazone. This practice is consistent with the FDA’s December 2008 Guidance for Industry that recommends that manufacturers of new treatments for diabetes carefully design their clinical trials to include an evaluation of cardiovascular safety.

Once the FDA has completed its review of rosiglitazone, the agency will present its findings at a joint public meeting of the Endocrinologic and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees in July 2010.

Rosiglitazone, a treatment for Type 2 diabetes, is sold as a single-ingredient product under the brand name Avandia, and is available in combination with other diabetes medications, such as metformin, under the brand name Avandament, or glimepride, under the brand name Avandaryl. The FDA advises that patients who are currently taking any form of rosiglitazone should not stop taking their medication without first talking to their healthcare professional. Any side effects with this or any other medication should be reported to the FDA MedWatch Adverse Event Reporting program at www.fda.gov/medwatch.

SOURCE: Avandia Recall › FDA announces it will review studies linking Avandia to heart attacks

Avandia was approved by the FDA for the treatment of Type 2 diabetes in 1999, and grew to become a $3 billion a year industry for GSK. In 2007, a study was published in the New England Journal of Medicine that linked Advandia to a 43 percent increased risk of heart disease. The senators contend that the London-based GSK got its hands on a copy of the report before it was published and the drug company quickly initiated a public relations push to counter any questions about Avandia’s link to increased heart risk. The drug company also urged the medical researchers who identified the risk of heart and liver problems in patients taking Avandia to stop publishing their findings.

The effort kept the drug on the market, but GSK took a near-$2 billion hit in sales in 2009. A company spokeswoman said in a statement, “the scientific evidence simply does not establish that Avandia increases ischemic cardiovascular risk or causes myocardial ischemic events … Based on the scientific evidence and a recommendation by an independent advisory committee of experts convened by the FDA, the agency has ruled that Avandia remain available to patients for the treatment of Type 2 diabetes.”

Senators Baucus and Crassley disagree. “It can be argued that GSK had a duty to warn patients and the FDA of the Company’s concerns,” wrote Baucus and Grassley in the Senate committee report. “Instead, GlaxoSmithKline executives attempted to intimidate independent physicians, focused on strategies to minimize or misrepresent findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that a competing drug might reduce cardiovascular risk.”

Sources:
Business Week
New York Times

SOURCE: Avandia Recall › Senators ask why dangerous Avandia was not pulled from market

The group enumerated its concerns in a full petition, citing both safety and efficacy issues. Adverse events linked to Avandia and listed in the petition include liver failure, myocardial ischemia (increased risk of heart attack), congestive heart failure, macular edema (vision loss), anemia, and bone fractures.

One new analysis of the FDA’s Adverse Event Reporting System (AERS) data revealed that of 14 Avandia users who experienced kidney failure, 12 died.

“The evidence for this unique combination of toxicities is compounded by the accompanying lack of evidence of any clinical benefit, compared to other approved drugs for diabetes,” the petition states.

The petition also refers to statements released earlier by both the American Diabetes Association and the European Association for the Study of Diabetes advising against the use of Avandia given the availability of better options.

To support its claim, Public Citizen also included a graph highlighting the dwindling sales of Avandia from the first quarter of 2006 to the second quarter of 2008. 13.3 million Avandia prescriptions were written in 2006, yet only 4.6 million were written in the last year. Avandia prescriptions have declined steadily since late 2006.

“The FDA is in possession of clear, unequivocal evidence that (Avandia) causes a wide variety of toxicities,” Public Citizen said in its petition to the FDA.

Drugmaker GlaxoSmithKline issued a response to the petition on Friday, standing by Avandia.

“The safety of patients using our medicine is very important to us. On a continual basis, an external Hepatic Safety Board reviews any adverse event report received by GSK of liver failure, liver-related deaths and liver transplants for possible relationship to AVANDIA. As recently as July 2008, this panel of experts continued to endorse a favorable hepatic safety profile for AVANDIA,” the statement said.

Public Citizen is a nonprofit consumer advocacy organization representing more than 80,000 consumers in the U.S. It was founded in 1971 to “represent consumer interests to Congress, the executive branch, and the courts.”

SOURCE: Avandia Recall › Consumer watchdog urges immediate Avandia ban

For years, GlaxoSmithKline, the manufacturer of Avandia, enjoyed stellar sales of the diabetes drug. Avandia was GSK’s second-best seller until the results of some studies surfaced that indicated the drug poses serious risks for its users.

In February of 2007, a press release issues by GSK announced a link between female users and increased risk of bone fractures, especially of the upper arms, hands, and feet.

In June of last year, an article in The New England Journal of Medicine reported that Avandia significantly increased the likelihood of heart attacks by 43% and death by cardiovascular diseases by as much as 64% in users.

The news dealt a devastating blow to Avandia. Estimates indicate that annual Avandia profits dropped by a billion pounds (nearly $1.8 billion U.S.). A growing number of lawsuits against GSK and competition from cheaper generics also threaten GSK’s numbers. It could be argued that while additional job cuts save the company some money, those cuts are only necessary to make the company’s numbers more attractive to investors.

According to the Hertfordshire Mercury, a GSK spokeswoman explained the cuts as “part of GSK’s longer-term strategy to ensure that we invest in key areas of future growth and evolve our business to compete effectively in what is a rapidly changing and challenging environment for pharmaceutical companies.”

Translated from CEO-speak, the statement seemingly alludes to all the problems pharmaceutical companies face these days — that they must appear extra-profitable to investors while sustaining aggressive ad campaigns amidst litigation and declining sales.

SOURCE: Avandia Recall › Avandia sales drop hurting GlaxoSmithKline

The maker of the drug, GlaxoSmithKline (GSK), disputes the osteoporosis finding. The company said in a statement today that their ADOPT studies showed no increase in spine or hip fractures which are associated with osteoporosis.

The company says they will be looking further into the subject.There are other possibly safer alternative treatments for diabetes, according to Paul Brandt, an associate professor of neuroscience and experimental therapeutics at Texas A&M Health Science Center College of Medicine. “Anyone who is already at risk for osteoporotic fractures should consider an alternative anti-diabetic drug.”

Amanda Gardner of HealthDay News reports that Avandia affects a key cellular protein called the peroxisome proliferator-activated receptor (PPAR-gamma). The mice studies by the Salk Institute for Biological Studies in La Jolla California found that activating this receptor stimulates the production of osteoclasts. These osteoclasts degrade bone.

Avandia recently received some bad press concerning the relation of the drug with heart problems. Avandia, along with four other drugs in the same class, were given blackbox warnings by the Food and Drug Administration (FDA). These warnings are the strictest advisories offered by the FDA for products that they have approved. The drug was linked to heart failure in some patients.

SOURCE: Avandia Recall › Type 2 diabetes drug Avandia linked to osteoporosis and bone loss

Details of this strange turn of events were about to be published in the journal Nature before US Senator Charles Grassley broke its embargo and issued a letter written to GSK asking the firm what action it had taken on receiving the article from Steven Haffner of the University of Texas Health Science Center in San Antonio. The NEJM piece linked Avandia (rosiglitazone) to a 43% increased risk in heart attacks and strokes and observers were struck by the speed and detail of GSK’s rebuttal. There would now appear to be an explanation, however.

The Nature article notes that Dr Haffner faxed his copy of the article 17 days before publication in the NEJM to Alexander Cobitz, a GSK employee he knew. “Why I sent it is a mystery,” Dr Haffner is quoted as saying. “I don’t really understand it. I wasn’t feeling well. It was bad judgement.” He notes that he has worked with the UK-based drugs giant many times, principally on the Avandia ADOPT study, but refutes the notion that his motivastion for the leak was cash. “I’ve got a considerable amount of money,” he said. “I didn’t do it to raise my income or anything like that.”

GSK spokeswoman Nancy Pekarek told Nature that she was not aware of anyone at the firm informing the journal of the confidentiality breach. She added that Dr Haffner had expressed concerns regarding the methodology of the analysis, and sent the article, written by Steven Nissen of the Cleveland Clinic, for advice.

Dr Nissen has expressed his disappointment over the confidentiality breach, as has Sen Grassley, a fierce critic of the relationship of the pharmaceutical industry with doctors and regulators. He said that “the most troubling aspect of this situation is that the integrity of another aspect of the scientific process is called into question – scientific peer review”.

January 31st, 2008 by Kevin Grogan with Pharma Times

SOURCE: Avandia Recall › GSK Sent Avandia meta analysis before publication

The moves by Prime Therapeutics and HealthTrans mark the latest example of U.S. healthcare providers deciding to limit access to the drug, following an earlier decision by the U.S. Department of Veterans Affairs to severely restrict use.

Such actions, particularly if followed by others, may further undermine sales of the once-popular medicine, which have been hit hard recently by a report linking it to heart attacks.

Prime and HealthTrans said in separate statements they had made their decisions after a thorough analysis of the clinical literature examining the safety and efficacy of Avandia.

“Prime takes drug safety warnings very seriously and our primary concern is the safety of our members,” said Craig Mattson, senior director of drug technology assessment and formulary development.

Britain-based Glaxo, Europe’s biggest drugmaker, said it was surprised and disappointed.

“It limits options for treatment and could be detrimental for patients. The FDA (Food and Drug Administration) has said the data remains inconclusive and therefore to limit patients’ options in this is disappointing,” a spokeswoman said.

Concerns about the safety of Avandia were triggered in May by a U.S. analysis linking it to a 43 percent higher risk of heart attack. Avandia was Glaxo’s second-biggest drug in 2006, with worldwide revenue of 1.6 billion pounds ($3.2 billion), but sales have plunged since May, with revenue in the United States down 48 percent in the third quarter from the year-ago period.

SOURCE: Avandia Recall › Two U.S. healthcare providers drop Glaxo’s Avandia

In a floor statement placed in the Senate record, Sen. Charles Grassley also said that safety watchdogs within the federal Food and Drug Administration “several months ago” recommended a “black box” on the drug’s label, the strongest possible warning.It is the first confirmation that the FDA’s own analysis of Avandia shows a similar magnitude of heart attack risks, dangers that were first publicly raised in a medical journal report published earlier this week.

Grassley complained that FDA higher-ups have said they want to wait for results of an ongoing study that will not be available for two more years before making a decision.

“That’s a long time from now when you have millions of Americans taking this drug,” said the statement by the Iowa Republican. “Those numbers seem like a high enough threshold to me for the FDA to warn the American people of the possibility of a problem.”

The FDA has been under fire since Monday’s report came out, attacked by consumer advocates for dropping the ball on drug safety and for taking no stronger action in light of the new warning signs.

Avandia, sold by the British company GlaxoSmithKline PLC, is a blockbuster medication used to treat Type 2 diabetes, the most common form of the disease. More than 6 million people worldwide have taken the drug, whose U.S. sales topped $2.2 billion last year.

On Monday, an analysis led by Cleveland Clinic cardiology chief Dr. Steven Nissen of 42 separate studies on Avandia concluded that it raised the risk of heart attacks by 43 percent, compared to the rates among people taking no or other diabetes drugs. The analysis also indicated that Avandia might increase the risk of heart-related deaths.

GlaxoSmithKline strongly disputes the conclusions. Company officials said that while their own similar analysis suggested a 31 percent greater risk _ information it shared with the FDA as early as 2005 _ more rigorous, albeit smaller, individual studies did not show that.

Critics have accused the FDA of being lax in monitoring drug safety, and some members of Congress scheduled hearings and have subpoenaed key people to appear.

Grassley’s staff has been meeting with FDA staffers and others and gathering documents all week to investigate the issue, said Jill Kozeny, press officer for the Senate Finance Committee, of which Grassley is ranking member.

FDA spokeswoman Julie Zawisza confirmed Thursday the internal analysis that Grassley’s statement revealed, but added, “we have conflicting data” from individual studies, and therefore “are continuing to review the results of GSK’s ongoing trial to determine the actual risk.”

She said she could not discuss “ongoing regulatory matters” like the black box warning that Grassley’s statement says was urged months ago by the FDA’s Division of Drug Risk Evaluation.

As for the number of heart attacks possibly linked to the drug _ as many as 20 a day, Grassley contends _ Zawisza said: “A relationship between the drug and these deaths has not been established. We don’t have data to support such a conclusion.”

Any increase in heart attack risk is especially worrisome for diabetics because two-thirds of them die of heart problems.

About 1 million Americans are currently taking Avandia, which costs from $90 to $170 for a one-month supply. The FDA and diabetes experts are advising users of the medication to talk to their doctors and not to immediately discontinue the drug, which helps keep blood-sugar levels under control.

May 24th, 2007 by Marilynn Marchione with The Associated Press

SOURCE: Avandia Recall › FDA study said to show Avandia risk