Yourlawyer.com (Avandia News)

Class Of Diabetes Drugs That Includes Avandia Linked To Fracture Risk

Wed, 30 Sep 2009 00:00:00 -0700

The risk of bone fracture in individuals taking thiazolidinediones has again been suggested in another recent study. Science Daily just reported that research published this week in PLoS Medicine discussed the risk between the type 2 diabetes drugs and bone fracture. Thiazolidinediones—known as TZDs—were introduced in the 1990s and include such popular medications as Avandia (rosiglitazone) or Actos (pioglitazone).

The study, led by Ian Douglas of the London School of Hygiene and Tropical Medicine—reviewed, said Science Daily, the General Practice Research Database, which is a listing of clinical records of over six million patients registered at 400 general practice surgeries in the United Kingdom.

The team located 1,819 patients aged 40 and older with a recorded bone fracture and who were also prescribed a TZD at least once. The team conducted a “self-controlled case-series study,” which compares the frequency of the event—a fracture—in a demographic over a certain time and when a specific medication—TZDs—is taken versus when the medication is not taken, explained Science Daily. The group was age-adjusted to allow for age-related fractures.

The study revealed that about one and half times as many fractures were reported when people took TZDs versus when TZDs were not taken, said Science Daily. The increased fracture risk occurred in both men and women and affected an array of body areas, reported Science Daily, which also noted that the risk was commensurate with the duration of treatment.

The team concluded that the study’s main advantage was that it removed the potential for differences between those who do and do not take a specific drug, said Science Daily, and that these findings are consistent with others studies in which the TZD-fracture connection was found. The researchers stated that the results "should be taken into consideration in the wider debate surrounding the possible risks and benefits of treatment with thiazolidinediones,” quoted Science Daily.

In August we reported on a large, panel study that also revealed an increased risk of fracture associated with TZDs. That study took place in British Columbia, Canada, and appeared in the Archives of Internal Medicine, according to The Heart. That research team looked at fracture risk in over 84,000 patients who received Avandia or Actos over a sulfonylurea, said The Heart. The study revealed that men and women experienced an increased risk of fractures when taking a TZD and found that Actos could actually be responsible for an increased fracture risk, said the Heart. The U.S. Food & Drug Administration (FDA) asked for a warning on the Actos labeling two years ago to address the risk, noted the Heart. As with the British study, this study found that the risk for fractures increased the longer the patient was on the medication.

In addition to its potential to cause fractures, Avandia has been linked to a long list of other safety concerns. In July we wrote that a prominent consumer advocacy group found that Avandia was associated with death due to liver failure. In June, we wrote about a published Avandia study that found the drug “significantly” raises the risk of heart failure and fractures. Avandia’s cardiovascular side effects first became the subject of concern in May 2007, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. That summer, GlaxoSmithKline and the FDA came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. In November 2007, a warning detailing Avandia’s association with myocardial ischemia was added to the drug’s boxed warning.

Greater Heart Failure Risk with Avandia, Study Finds

Mon, 28 Sep 2009 00:00:00 -0700

Another study involving Avandia has found an increased risk of heart failure among patients taking the controversial diabetes drug. The Canadian study was published this month in the British Medical Journal.

Avandia’s cardiovascular side effects first became the subject of concern in May 2007, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. That summer, GlaxoSmithKline and the Food & Drug Administration (FDA) came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. In November 2007, a warning detailing Avandia’s association with myocardial ischemia was added to the drug’s boxed warning.

This latest study involved 39,494 patients, aged 66 and older, who were started on either Avandia or Actos between April 2002 and March 2008. Researchers in Toronto, Ontario found that patients treated with Actos had a 23 percent lower risk of being hospitalized for congestive heart failure, and a 14 percent lower risk of death from any cause. There was no significant difference in the risk of heart attack. During the six-year study period, 5.3 percent of patients taking Actos and 6.9 percent taking Avandia either died or were hospitalized for heart attack or congestive heart failure.

"Given the accumulating evidence of harm with rosiglitazone (Avandia) therapy and the lack of a distinct clinical advantage for the drug over pioglitazone (Actos), it is reasonable to question whether ongoing use of rosiglitazone is justified in any circumstance," the researchers report.

The study's principle investigator, Dr. David Juurlink, a scientist at the Institute for Clinical Evaluative Sciences in Toronto, and head of the division of clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre, told the Calgary Herald that the increased risk from Avandia could be significant. "If a million patients were treated with rosiglitazone (Avandia) rather than pioglitazone (Actos), these results imply that we would see more than 8,000 excess admissions for heart failure, and more than 3,000 additional deaths from any cause," Juurlink says.

Jurrlink also told the Calgary Herald that his practice was to never start patients on Avandia, and to switch patients on Avandia to medications that he considers to be safer.

Avandia Riskier for Elderly, Canadian Study Says

Wed, 19 Aug 2009 00:00:00 -0700

The diabetes drug Avandia carries more risk than Actos, a new study conducted by Canadian researchers has found. According to a Reuters report, seniors in the study taking Avandia were more likely to suffer from heart failure, and were more likely to die. The findings prompted the authors of the study to question the continuing use of Avandia.

According to Reuters, researchers at Sunnybrook Health Sciences Centre in Toronto analyzed six years of records for nearly 40,000 patients aged 66 years and older. They found that for every 93 patients given Avandia rather than Actos there would be one additional cardiovascular event or death each year. No significant difference in the risk of heart attack between Avandia and Actos was found.

"Given the accumulating evidence of harm with rosiglitazone (Avandia) treatment and the lack of a distinct clinical advantage for the drug over pioglitazone (Actos), it is reasonable to question whether ongoing use of rosiglitazone is justified," the study authors wrote in the British Medical Journal.

Avandia’s cardiovascular side effects first became the subject of concern in May 2007, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. That summer, GlaxoSmithKline and the Food & Drug Administration (FDA) came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. In November 2007, a warning detailing Avandia’s association with myocardial ischemia was added to the drug’s boxed warning.

Avandia has been focus of other safety concerns. In July we reported that a prominent consumer advocacy group had found that Avandia had been associated with death as a result of liver failure, and should be banned by the FDA. The group, Public Citizen, published the research in the peer-reviewed medical journal Pharmacoepidemiology and Drug Safety. According to Public Citizen, it petitioned the FDA to ban Avandia as far back as October due to its risks, including heart attack, heart failure, and liver toxicity, noting that these risks “far outweigh its benefits,” especially given that there are safer medical alternatives for the treatment of Type 2 diabetes. The study discussed 11 cases of severe liver toxicity, mostly fatal, that were associated with Avandia use, said Public Citizen.

In June, we wrote about a published Avandia study that found the drug “significantly” raises the risk of heart failure and fractures. Unlike previous research, the study did not find that people taking Avandia were at a higher risk of heart death, and was unable to determine if the Avandia patients in the study had a higher chance of heart attack. According to a report on WebMD, the study—known as RECORD—caused some controversy because GlaxoSmithKline funded it.

Group Says Avandia Ups Risk For Liver Damage

Wed, 29 Jul 2009 00:00:00 -0700

According to emerging research, GlaxoSmithKline’s diabetes drug, Avandia, can cause death as a result of liver failure, and should be banned by the U.S. Food & Drug Administration (FDA). The group, Public Citizen, published the research in the peer-reviewed medical journal Pharmacoepidemiology and Drug Safety.

According to Public Citizen, it petitioned the FDA to ban Avandia as far back as October due to its risks, including heart attack, heart failure, and liver toxicity, noting that these risks “far outweigh its benefits,” especially given that there are safer medical alternatives for the treatment of Type 2 diabetes. The study discussed 11 cases of severe liver toxicity, mostly fatal, that were associated with Avandia (generic: rosiglitazone) use, said Public Citizen.

Public Citizen identified the 11 cases following review of MedWatch forms submitted to the FDA’s Adverse Event Reporting System (AERS) between 1997 and 2006, it said, noting that such forms are provided to the FDA by patients and health care providers when a suspicion of adverse drug reactions exits. "Because of low reporting rates to the AERS database, the 11 cases likely represent a small fraction of patients who developed liver failure because of the drug," said Dr. James Floyd, a Public Citizen health researcher and lead author of the study, quoted the group. "Our best estimate is that one case of liver failure occurs for every 44,000 patients who take Avandia," Dr. Floyd added.

Last month we wrote about a published Avandia study that found the drug “significantly” raises the risk of heart failure and fractures. Unlike previous research, the study did not find that people taking Avandia were at a higher risk of heart death, and was unable to determine if the Avandia patients in the study had a higher chance of heart attack. According to a report on WebMD, the study—known as RECORD—is causing some controversy because GlaxoSmithKline funded it.

This past October, a Public Citizen working group, with representatives from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes unanimously advised against Avandia. Public Citizen discourages diabetics from taking Avandia because of increased risks for liver toxicity; heart attack (about 40 percent); heart attack and fractures (double); and anemia and vision loss from macular edema; retinal swelling when fluids accumulate in the eye. According to Public Citizen, there were 39 times more reports of macular edema per million prescriptions for Avandia versus the diabetes drug, glipizide.

"The research is yet another indication that Avandia is too dangerous to remain on the market," said Dr. Sidney Wolfe, acting president of Public Citizen, director of Public Citizen’s Health Research Group, and co-author of the study, quoted the group. "The FDA’s new leadership should demonstrate its commitment to public health by banning this drug, thereby preventing needless deaths and serious adverse events."

Avandia’s cardiovascular side effects have been the subject of concern since May 2007, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. That summer, GlaxoSmithKline and the FDA came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. In November 2007, a warning detailing Avandia’s association with myocardial ischemia was added to the drug’s boxed warning.

Glaxo-Funded Avandia Study Adds to Controversy

Mon, 08 Jun 2009 00:00:00 -0700

A newly published Avandia study has found that the controversial diabetes drug "significantly" raises the risk of heart failure and fractures. But unlike previous research, this study did not find that people taking Avandia were at a higher risk of heart death, and was unable to determine if the Avandia patients in the study had a higher chance of heart attack. However, according to a report on WebMD, the study - known as RECORD- is causing some controversy because it was funded by GlaxoSmithKline, the maker of Avandia.

Avandia’s cardiovascular side effects have been the subject of concern since May 2007, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. That summer, GlaxoSmithKline and the Food & Drug Administration (FDA) came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. In November 2007, a warning detailing Avandia’s association with myocardial ischemia was added to the drug’s boxed warning.

Concerns over Avandia's safety had prompted the American Diabetes Association to advise against prescribing Avandia in favor of Actos, another drug in the same class, WebMD said. But now, the Association may reconsider that stance in light of the RECORD study.

According to an article on usnews.com, the Website of U.S. News and World Report, the RECORD study involved 4,447 patients with type 2 diabetes, randomly selected to take Avandia plus metformin and sulfonylurea or just metformin and sulfonylurea. The study was not blinded, meaning that study investigators and patients knew which treatment they were getting, WebMD said.

At a news conference announcing the RECORD results, Dr. Philip D. Home, chairman of the study steering committee and a professor of diabetes medicine at Newcastle University in Britain said Avandia "clearly has a role, alongside other drugs [in the treatment of diabetes], provided you obey the contraindications, which are not to use it in people with heart failure and to think twice for people at high risk for fractures."

But not everyone is so sure. Dr. Stephen Nissen, who conducted the 2007 study that first found an increase risk of heart attacks among Avandia users, is among them. According to usnews.com, Nissen called the RECORD study "seriously flawed" because more patients in the Avandia group were taking cholesterol-lowering statins and that group had what looked to be a high drop-out rate. "Obviously, it is impossible to assess the safety of a drug when patients are not actually taking it," Nissen said.

In the same report, Dr. Suzanne Steinbaum, director of women and heart disease at Lenox Hill Hospital in New York City, said that determining which patients might safely use Avandia might prove difficult, as type2 diabetes already puts people at a higher risk of heart disease.

Avandia Lawsuits Filed in Illinois, Texas

Fri, 29 May 2009 00:00:00 -0700

Avandia lawsuits continue to be filed in courts around the country. Two just filed in Illinois involve a whopping 186 plaintiffs. Another Avandia lawsuit in Texas claims the dangerous diabetes drug is not worth its risks.

Avandia’s cardiovascular problems have been the subject of concern since May 2007, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. That summer, GlaxoSmithKline, the maker of Avandia and the Food & Drug Administration (FDA) came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. In November 2007, a Black Box warning detailing Avandia’s association with myocardial ischemia was added to the drug’s labeling.

Since the May 2007 study highlighting Avandia's heart risks was released, thousands of people injured by the drug have filed lawsuits against Glaxo. The two Illinois lawsuits were filed May 15 in Illinois state court. The 186 plaintiffs in the lawsuits allege Glaxo failed to warn of potential serious side effects from which they or their deceased relatives suffered.

As a result of their ingestion of the drug, the plaintiffs say they became ill and were impaired in their health, strength and activity. They also incurred medical costs, lost wages, suffered disabilities and experienced pain, according to the complaints. The plaintiffs maintain Glaxo should have provided warnings on Avandia's heart risk before the FDA required the company to do so, especially since the company knew that most people with diabetes have risk factors such as high blood pressure and cholesterol that provide a susceptibility for heart disease and stroke.

In both Illinois lawsuits, the plaintiffs are seeking a judgment in excess of $450,000, plus costs, attorney's fees and other relief the court deems just.

The Texas lawsuit, filed on May 13 in the U.S. District Court of the Eastern District of Texas, Texarkana Division, involves a man who had to have heart bypass surgery after having taken Avandia for five years. The lawsuit alleges that Glaxo employed "spectacular" marketing and distribution strategy despite knowing that "its drug was unreasonably dangerous and that the diabetic patient population was uniformed of the dangers."

"Defendant Glaxo did not provide sufficient warnings and instructions that would have put Plaintiff and the general public, on notice of the dangers and adverse effects caused by ingesting [Avandia], including without limitation to risk of heart attack," the lawsuit states.

The lawsuit claims that Avandia is defective in design and unreasonably dangerous and states that the risks of using Avandia far outweighed the benefits.

Internal Emails Confirm Glaxo Avandia Cover-Up

Wed, 14 Jan 2009 00:00:00 -0800

Recent reports point to GlaxoSmithKline long being aware of Avandia’s cardiac risks. In 2007, a Cleveland Clinic study conducted by prominent cardiologist Dr. Steven Nissen and published in the New England Journal of Medicine (NEJM) found that patients taking the diabetes drug experienced a 43-percent higher risk of suffering a heart attack. Many called for Avandia’s recall, but as Wall Street Journal (WSJ) reports today, Glaxo argued against the findings. Now, some details of Glaxo's behind-the-scenes Avandia cover-ups are being made public.

Glaxo emails prove its own researchers were worried its findings mirrored Nissen’s study says the WSJ. Following release of the study, both Glaxo and the U.S. Food & Drug Administration (FDA) came under fire for a failure to warn the public about Avandia’s risks. Also, 2007 Congressional testimony revealed both groups knew about the cardiac risks in 2005 and an FDA scientist who advocated for a strong black box warning alleged that the damaging information was removed from an Avandia safety review. Just before the study was published, reports WSJ, Glaxo’s senior consultant wrote in an email, "The numbers are the numbers, the analysis is very similar to our own."

Despite overwhelming evidence to the contrary, Glaxo and the FDA continue to defend Avandia. Janet Woodcock, FDA drug review division director, recently said that Avandia was "convicted without a trial," quoted the WSJ. Glaxo also maintains it did not hide that it conducted its own meta-analysis and found similar cardiac results as the study and that it provided the information to the FDA.

Meanwhile Senator Chuck Grassley—Repubican-Iowa—has been after the FDA to have Glaxo withdraw Avandia and is working on a report expected to contain information from Glaxo’s own documents on its efforts to defend Avandia, said the WSJ, which noted that about 1,000 patients have filed suit against Glaxo. The WSJ reported that the study was to be kept secret until its late-May 2007 release; however, Glaxo got hold of it in advance from University of Texas Dr. Steven Haffner, a Glaxo Avandia consultant since 2000, who reviewed the piece for the NEJM. Haffner acknowledged he gave Glaxo the study in advance and said his action was "a terrible mistake."

Dr. Nissen told the WSJ that he was visited by some top members of Glaxo’s scientific team, including its chief medical officer, just prior to the piece’s publication and was asked to rethink his conclusions. Said Nissen, "They never revealed that they had obtained a copy of our manuscript and had concluded that our findings were irrefutable. Instead, they attacked the validity of the study and the motives of both the authors and the NEJM."

The WSJ also released a number of damaging email excerpts. For instance, one email stated that, "There is no statistical reason for disregarding the [Nissen] findings as presented" and Moncef Slaoui’s, director of Glaxo research, said: "FDA, Nissen and GSK all come to comparable conclusions regarding increased risk for ischemic events, ranging from 30% to 43%!"

Defending itself from Nissen’s conclusion, WSJ reported that Glaxo released interim results of a study called “Record”; however some at Glaxo were concerned this would fail and one scientist’s email states, “What's to stop [Nissen] adding the events from Record to his meta-analysis and re-enforcing his view?” The NEJM, after receiving the Record results from Glaxo responded with: "The editors feel strongly that your data do not support the statement that the Record results for MI [myocardial infarction or heart attack] contradict the Nissen meta-analysis…. This statement must be removed or modified," quoted the WSJ. So, Glaxo responded with a revision that said the drug might be linked to higher cardiac risks but did not increase the risk of heart attack or death, said WSJ. The NEJM included an editorial by Massachusetts General Hospital endocrinologist David Nathan, which said the study "fails to provide exculpatory evidence" about Avandia, noting that too many participants left the drug trial.

The FDA is also facing some heat. At a June 2007 Congressional hearing, FDA commissioner, Andrew von Eschenbach, defended the FDA’s refusal to remove Avandia from the market or significantly strengthen its warning saying that the agency’s own analysis was in progress, reported the WSJ. In a clear contradiction, a press release issued by the agency claimed it had only recently received information from Glaxo about its 2005 meta-analayis; however, the FDA received that data a year before the NEJM according to Glaxo emails and a Glaxo statement this week, the WSJ said.

The WSJ reports that the FDA declined to comment and Glaxo refused to make employees connected with the damaging emails available to it for comment.

FDA Wants New Diabetes Drugs Tested for Heart Risks

Thu, 18 Dec 2008 00:00:00 -0800

New diabetes drugs will now have to be screened for heart risks before they can be approved, the Food & Drug Administration (FDA) said yesterday. The new testing standards do not apply to drugs already on the market, including Avandia and Actos, two medications that have been linked to heart problems.

According to the FDA, more than 23 million people in the United States have been diagnosed with type 2 diabetes or diabetes mellitus, a chronic metabolic disorder characterized by abnormally high blood sugar levels known as hyperglycemia.

Patients with diabetes have a two- to four-times greater risk of heart disease than their non-diabetic counterparts, and the FDA said that none of the diabetic medications currently on the market has been convincingly proven to reduce that risk. Because diabetes often requires life-long treatment, prescribers and patients need to know more about whether their antidiabetic therapies put patients at increased risk of heart attack, the agency said.

The FDA decided to take a look at diabetes drug testing after Avandia was linked to an increased risk of heart attacks. Previously, the FDA required the makers of diabetes drugs to prove they lower blood sugar levels. But the Avandia debacle has led many experts to call on the agency to require drug makers to meet other bench marks, including whether they reduce the risk of cardiovascular problems - the number one killer of diabetics.

"We need to better understand the safety of new antidiabetic drugs. Therefore, companies should conduct a more thorough examination of their drugs' cardiovascular risks during the product's development stage," Mary Parks, M.D., director of the FDA Division of Metabolism and Endocrinology Products, Center for Drug Evaluation and Research, said in a statement announcing the new standards. "FDA's guidance outlines the agency's recommendations for doing such an assessment."

The new guidance, which is effective immediately, defines more robust and adequate design and data collection approaches for Phase 2 and Phase 3 clinical trials than were previously required. Specifically, the FDA recommends that these studies demonstrate that new antidiabetic therapies do not increase cardiovascular risk in comparison with existing therapies -- especially when the drugs are used by patients of advanced age or by those with advanced diabetes or renal impairment.

The FDA also recommends that manufacturers have any cardiovascular events in their clinical trials analyzed by committees of outside cardiologists who are unaware of which patients received the tested products and which were on placebo. Based on these evaluations, the FDA can better ensure that product labeling includes comprehensive information on safety and effectiveness. This will enable prescribers and patients to make better-informed decisions on the management of type 2 diabetes.

The FDA has provided written notice of the recommendations to more than 100 manufacturers who have submitted investigational new drug applications for type 2 diabetes treatment. The new standards mean that it could take longer for drug makers to bring these new medications to market.

Avandia, Actos Raise Fracture Risk for Women

Wed, 10 Dec 2008 00:00:00 -0800

Women who take the diabetes drugs Avandia and Actos face a higher risk of bone fractures, a new study has found. The fracture problem is just the latest troubling side effect associated with these drugs, which have also been linked to heart problems.

For the study, researchers at North Carolina's Wake Forest University School of Medicine and the University of East Anglia in Britain analyzed 10 previous clinical studies lasting at least a year involving 14,000 patients. According to USA Today, the researchers determined that taking either Avandia or Actos for a year doubled the risk of fractures in women. For those in their 70s, - a group already at a higher risk for fractures - the researchers estimated that one fracture would occur for every 21 women. In women in their mid-50s, the figure equals one fracture in every 55 women.

No increased risk was seen among men who took Avandia or Actos. The researchers speculated that the drugs' interaction with estrogen may have led to weaker bones in women. They called for stronger warnings on drugs' labels about the increased fracture risk.

Both Avandia and Actos are associated with other serious side effects. The labels of both drugs carry strong warnings about their link to heart failure. In May 2007, an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking Avandia had a 43-percent higher risk of having a heart attack. In November 2007, the Food & Drug Administration (FDA) finally ordered that a black box warning detailing Avandia’s heart related risk be added to the drug’s labeling.

In October, the group Public Citizen said it had identified 14 cases of Avandia-induced liver failure in the FDA’s Adverse Event Reporting System. Of the 14 cases of liver failure, 12 resulted in deaths. Those findings prompted Public Citizen to file a petition with the FDA asking that Avandia be removed from the market. The liver failure associated with Avandia, taken together with the drug’s risk of other side effects, including heart failure, fractures and vision loss, was too great to allow the drug to continue to be sold in U.S., the group’s petition said.

In October, the American Diabetes Association/European Association for the Study of Diabetes working group dropped Avandia from its treatment guidelines.

Avandia Linked with Increased Risk of Death, Heart Attacks

Tue, 25 Nov 2008 00:00:00 -0800

According to a study published in a recent issue of the Archives of Internal Medicine, the diabetes drug rosiglitazone maleate—also known as Avandia—may increase the risk of certain cardiovascular events.

The study, which was conducted by Dr. Wolfgang Winkelmayer of Brigham and Women's Hospital in Boston and colleagues, involved patients aged 65 and older who had taken either Avandia or Actos (pioglitazone hydrochloride) for one year. Both Avandia and Actos belong to the same class of diabetes drugs. Both now contain warning labels about using the medications in patients with existing heart failure.

According to CBCNews.Ca, medical claims data for 28,361 patients were reviewed by the research team—14,260 took Actos; 14,101 took Avandia. Avandia patients experienced an increased likelihood of death at a rate of 15 percent and a 13 percent increased risk of heart failure, versus those taking Actos. According to CBCNews.Ca, the Avandia group experienced 1,869 deaths, while only 885 died in the Actos group. Avandia is made by GlaxoSmithKline and Actos is made by Takeda Pharmaceuticals North America In

In May 2007, a New England Journal of Medicine study concluded that Avandia increased the risk of cardiovascular problems in those who took it. U.S. News and World Report noted that the increased risk was at 42 percent and that, based on the study, Avandia might be riskier than Actos.

Both drugs are part of a class of drugs called thiazolidinediones, which are used to lower blood sugar in patients with type 2 diabetes. According to U.S. News and World Report, the U.S. Food and Drug Administration said that GlaxoSmithKline had agreed to add to the existing "black box" an additional warning about the potential increased risk for heart attacks when taking Avandia.

Winkelmayer says that both Actos and Avandia should be used with caution, with extra caution exercised for heart patients, and that neither drug should be prescribed as initial treatment, according to U.S. News and World Report. Dr. Eric J. Topol, director of the Scripps Translational Science Institute and chief academic officer at Scripps Health in La Jolla, California, agrees, “The study reinforces the heart failure risk of rosiglitazone versus pioglitazone," Topol told U.S. News and World Report.

Winkelmayer's study was supported by the American Heart Association and Satellite Healthcare Inc. The researchers also received grants from the pharmaceutical companies Amgen, Fresenius Medical Care, and GlaxoSmithKline/

CBCNews.Ca noted that the American Diabetes Association and a European counterpart dropped Avandia from a list of recommended treatments for people with Type 2 diabetes last month.

Another Avandia Critic Says Drug Maker Tried To Shut Her Up

Wed, 19 Nov 2008 00:00:00 -0800

Another doctor has come forward to claim that the maker of Avandia tried to silence her criticism of the controversial diabetes drug, The Wall Street Journal reports.   This time, an internist at a Hagerstown, Maryland hospital says drug company executives wrote to her superiors to get her to stop talking about her concerns that Avandia was linked to congestive heart failure and other problems.

Avandia’s cardiovascular problems have been the subject of concern since May 2007, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. That summer, GlaxoSmithKline, the maker of Avandia and the Food & Drug Administration (FDA) came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia.

Last year, we reported that a Senate Finance Committee was investigating whether or not the drug comany tried to silence Dr. John Buse, a diabetes expert and professor of medicine at the University of North Carolina in Chapel Hill. In 1999, Dr. Buse began expressing concerns about the cardiovascular risks of Avandia.   The summer before that report was published, the Senate committee heard testimony from Dr. Buse, who said he felt pressured by the drug’s maker, SmithKlineBeecham (now part of GlaxoSmithKline) to sign a clarifying statement drafted by the company that downplayed his concerns. During his testimony, Dr. Buse described name-calling and what he said was the veiled threat of a lawsuit by a high-ranking drug company executive after he had criticized Avandia at a medical meeting. Dr. Buse also testified that the drug complained about him to his supervisors at the University of North Carolina.

Now, internist Mary Money has told The Wall Street Journal about her experience with Glaxo after she and a colleague voiced concerns about Avandia back in 2000. According to Dr. Money, she and another doctor, Stephen Lippman, at Washington County Hospital in Hagerstown, met with representatives of SmithKlineBeecham, and presented data on 85 of their Avandia patients. According to The Wall Street Journal, more than half of the patients had significant edema, or swelling, and about half of that group also had high pulmonary pressure and shortness of breath. Three had been hospitalized for congestive heart failure.

Dr. Money told the Journal that the representatives from the drug maker dismissed her concerns. What's more, the next month, the drug maker wrote to the hospital's chief of staff in an attempt to force Dr. Money to stop talking about her worries with other doctors.

Fortunately, Dr. Money's superiors chose to trust her judgment, and ignored SmithKlineBeecham's letter.    According to the Journal, Dr. Money has continued to discourage the use of Avandia when speaking to colleagues.

Avandia Disappoints Again, Doesn't Significantly Reduce Arterial Plaque

Thu, 13 Nov 2008 00:00:00 -0800

Avandia, GlaxoSmithKline's controversial diabetes drug, does not reduce arterial plaque buildup in any significant way, according to a new study. This news only adds to the uncertainty surrounding Avandia, which has been the subject of safety worries since it was tied to an increased risk of heart attacks by another study in 2007.

Results from this latest Avandia clinical trial were detailed Wednesday at an American Heart Association conference by lead researcher Dr. Richard Nesto of Lahey Clinic in Burlington, Mass. and Brigham and Women's Hospital. The study, which involved 672 patients, compared Avandia's impact on arterial plaque buildup - a condition called atherosclerosis - to glipizide. Glipizide is an older diabetic drug that is available generically.

Though Avandia did seem to reduce plaque buildup slightly better than the older drug, the difference was not statistically significant, and could have happened by chance. After 18 months of treatment, those who took Avandia had an 0.21 percent reduction in plaque at the observed artery, while glipizide patients experienced an 0.43 percent increase in plaque.

Even before this new study was released, Avandia already faced serious questions over its safety. Avandia's trouble started in May 2007, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. In November 2007, the Food & Drug Administration (FDA) finally ordered that a black box warning detailing Avandia's heart related risk be added to the drug's labeling.

Late last month, the group Public Citizen said it had identified 14 cases of Avandia-induced liver failure in the FDA’s Adverse Event Reporting System. Of the 14 cases of liver failure, 12 resulted in deaths. Those findings prompted Public Citizen to file a petition with the FDA asking that Avandia be removed from the market.

The liver failure associated with Avandia, taken together with the drug’s risk of other side effects, including heart failure, fractures and vision loss, was too great to allow the drug to continue to be sold in U.S., the group’s petition said.

“The scientific evidence against Avandia is overwhelming,” Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group, said in a news release. “The timing of these findings should give the FDA the momentum it needs to act swiftly to prevent further needless deaths and health damage by banning this drug.”

Public Citizen is just the latest group to criticize Avandia. In October, the American Diabetes Association/European Association for the Study of Diabetes working group dropped Avandia from its treatment guidelines.

James Stein, an expert in cardiovascular imaging technologies at the University of Wisconsin, Madison, told Forbes.com that the findings of this latest Avandia clinical trial raised questions about Avandia's usefulness.

"There's really no reason anybody should be using this medicine," says Stein. "It's time to give this drug a rest. There are better, safer alternatives."

New Diabetes Drugs More Expensive, But Not Always Better

Tue, 28 Oct 2008 00:00:00 -0700

A new report has found that the cost for treating diabetes has skyrocketed, despite inconclusive evidence that newer, more expensive treatments provide added benefits to patients.

In 2002, diabetes accounted for more than 10 percent of U.S. health-care expenditures, and that number is expected to increase as the number of people with type 2 diabetes grows. According to the study conducted by researchers at the University of Chicago and Stanford University, between 2001 and 2007, spending for drugs went from $6.7 billion to $12.5 billion.

"We found dramatic changes in the treatment patterns for diabetes during the past decade," study author Dr. G. Caleb Alexander, an assistant professor of medicine at the University of Chicago, told The Washington Post. "This includes a remarkable change in drugs, as well as significant increases in costs."

The study attributes much the increased treatment costs to expensive new drugs, which can be 8 to 11 times more costly than older, generic diabetes drugs. Such drugs, including Januvia, Byetta and Avandia, are marketed as being more convenient and offering better control of blood sugar than the older medicines. In many cases the new drugs are being used instead of insulin, the use of which dropped from 38 percent in 1994 to 28 percent in 2007.

However, it is not clear just how much these new drugs are actually benefiting patients. "There are some real innovations here," Alexander said. "But we don't know enough about the comparative effectiveness of these medicines compared with older medicines to make a final verdict."

In some cases, new diabetes drugs are found to have dangerous side effects after they are approved and have been prescribed to millions of people. For instance, recently the diabetes drugs Avandia and Byetta have been the subject of safety concerns. On August 18, the FDA said that Byetta had been linked to 6 cases of hemorrhagic or necrotizing pancreatitis in patients taking Byetta since its October alert. All patients required hospitalization, two patients died and four patients were recovering at time of reporting. Byetta was discontinued in all 6 cases. Then, on August 26, Amylin announced that four additional fatalities had been confirmed in Byetta patients suffering from milder forms of pancreatitis.

Concerns about Avandia arose in 2007, after a New England Journal of Medicine revealed data linking Avandia to an increased risk of heart attack. Avandia, which has been on the market since 1999, has long carried warnings of its cardiovascular side effects, such as an increased risk for congestive heart failure and GlaxoSmithKline has known about concerns over Avandia’s heart attack risks since at least 2004; however, the heart attack risk was not mentioned in Avandia’s packaging information until November. The FDA raised existing warnings about congestive heart failure after the New England Journal’s publication triggered a congressional inquiry.

Patients Sue Glaxo Claiming it Suppressed Data on Avandia

Wed, 09 Jul 2008 00:00:00 -0700

Two North Carolina patients have sued GlaxoSmithKline claiming its diabetes drug, Avandia, caused their heart attacks. Hundreds more are seeking compensation for health problems they experienced after taking Avandia. The patients blame Glaxo for not adequately warning of all of the pill's cardiovascular risks.

Glaxo "knew of these dangerous effects in Avandia from the many trials which they performed and to which they had access and from their own analysis of these studies," the lawsuit reads. "But [the company] took no action to adequately warn or remedy the defects, but instead concealed, suppressed and failed to disclose these dangers." The lawsuit also claims that doctors and patients didn't have the information they needed to assess Avandia's risks and that Glaxo sales representatives minimized Avandia’s side effects. Also according to the lawsuit, one patient involved took Avandia from April 2006 until she was admitted to the hospital because of a heart attack in February 2007; she has since developed congestive heart failure. The other patient took Avandia from 2000 to 2007; in 2002 she suffered a heart attack and required triple bypass surgery.

A study published in May 2007 by the New England Journal of Medicine revealed data linking Avandia to an increased risk of heart attack. Since the report’s publication, Avandia prescriptions dropped over 50 percent. Avandia, which has been on the market since 1999, has long carried warnings of its cardiovascular side effects, such as an increased risk for congestive heart failure and Glaxo has known about concerns over Avandia's heart attack risks since at least 2004; however, the heart attack risk was not mentioned in Avandia's packaging information until November. The FDA raised existing warnings about congestive heart failure after the New England Journal's publication triggered a congressional inquiry.

Meanwhile, according to researchers recently comparing the results of two diabetes trials, weight gain, the use of multiple drug combinations, and even lowering blood sugar too low, too fast may have been factors in causing early deaths. Both trials, one conducted in the United States and Canada, the other in Australia, were designed to measure the benefits of using drugs such as Avandia to dramatically lower blood sugar in diabetes patients.

The trials followed over 21,000 diabetics, using multiple drugs—including Avandia. While cutting kidney disease in one trial, the treatments—which included Avandia—failed to protect diabetics from heart disease and stroke in the second. Avandia was given to 90 percent of the intensive therapy group in the second—Accord—trial. Both studies, the largest ever for diabetes, were recently published by the New England Journal of Medicine. The US trial, called Accord, was stopped in February when researchers found patients were more likely to die with aggressive treatment, which included the controversial diabetes medicine, Avandia. The most frequently used drug in the two trials was Avandia.

In April, the FDA issued a warning to Glaxo for not reporting safety results on Avandia saying that between 2001 and 2007 GlaxoSmithKline neglected to update the FDA on over 10 ongoing Avandia studies, as required by regulations.

Diabetes Drugs Need Tougher Testing for Heart Risk, FDA Panel Says

Mon, 07 Jul 2008 00:00:00 -0700

Last week, a Food & Drug Administration (FDA) advisory panel voted to back tougher testing requirements for diabetes drugs. In a 14-2 vote, which came late last Wednesday at the end of 2-day meeting, the outside experts recommended that diabetes drugs undergo more thorough safety reviews to ensure they don't raise the risk of heart problems. The panel also recommended that after approval, the makers of diabetes drugs conduct long-term studies to assess heart risks, even if initial clinical trials have not turned up such issues.

The FDA decided to take a look at diabetes drug testing after one popular medication - Avandia - was linked to an increased risk of heart attacks. Currently, the FDA requires the makers of diabetes drugs to prove they lower blood sugar levels. This outcome is known as a surrogate endpoint, because it was thought that lowering blood sugar would have a positive effect on cardiac risks and life span - the true goals of a diabetes drug. But the Avandia debacle has led many experts to call on the agency to require drug makers to meet other bench marks, including whether they reduce the risk of cardiovascular problems - the number one killer of diabetics.

Last Tuesday, Dr. Stephen Nissen, whose study published last May uncovered the Avandia safety issues, told the FDA advisory panel that it was time to toughen testing standards. “Merely lowering blood-glucose levels in diabetes is too simplistic,” Dr. Nissen said. “We must reduce the complications of diabetes, including cardiovascular disease.” Cardiovascular disease is the leading cause of death among diabetics.

The FDA panel did not recommend that diabetes drugs should show a benefit to patients' cardiovascular health, citing FDA evidence that no diabetes drug has shown such a benefit.

Drug makers are less than happy about this development. If the FDA adopts the panel's recommendations, additional clinical trials could add years and millions of dollars to the development of any new type 2 diabetes drug.

The FDA is not bound to follow recommendations from its advisory panels, but in most cases, it does so.

Avandia Debacle Prompts FDA to Consider New Rules for Approving Diabetes Drugs

Mon, 30 Jun 2008 00:00:00 -0700

Federal regulators are mulling over new rules for approving diabetes drugs. The new regulations the Food & Drug Administration (FDA) is considering include requiring that new diabetes drugs have a positive impact on cardiovascular disease and life span. The push for new rules comes a little over a year after a study found that Avandia - a popular diabetes drug marketed by GlaxoSmithKline - raised cardiovascular risks and probably did little to improve the life span of the people taking it.

Avandia has been a subject of controversy since May 2007, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. In June 2007, Congress held hearings to discuss the FDA's handling of its safety issues. At those hearings, it was revealed that in 2005 GlaxoSmithKline had informed the FDA of a study it had conducted that produced similar results. However, both the agency and the manufacturer felt that more investigation was needed before conclusions could be made about Avandia’s possible safety issues. Thus, the public was not made aware of the Avandia heart attack risk until the publication of the Cleveland Clinic article.

Currently, the FDA requires the makers of diabetes drugs to prove they lower blood sugar levels. This outcome is known as a surrogate endpoint, because it was thought that lowering blood sugar would have a positive effect on cardiac risks and life span - the true goals of a diabetes drug. But the Avandia debacle has led many experts to call on the agency to require drug makers to meet other bench marks, including whether they reduce the risk of cardiovascular problems - the number one killer of diabetics.

The issue of what benchmarks the FDA should use to approve diabetes drugs will be the topic of a special two-day meeting of FDA officials and outside medical experts set to start Tuesday. The FDA will also consider if the makers of diabetes drugs currently on the market, including Glaxo, should conduct additional studies on whether there are long-term cardiac risks with their products. According to The Wall Street Journal, scheduled speakers at the meetings include several doctors who have questioned the validity of surrogate end points. One, cardiologist Steven Nissen of the Cleveland Clinic, authored a 2007 Avandia study.

The practice of allowing surrogate endpoints to approve new drugs was also questioned this year when Vytorin, a blockbuster cholesterol lowering medication, was found to be ineffective in preventing clogged arteries. Vytorin had been approved on the basis that it lowered bad cholesterol. It was thought that would correlate to a decrease in the amount of arterial plaque in patients taking the drug. But a study released in January showed that assumption to be wrong.

Ketek, Avandia Among Drugs Doctors Won't Take

Mon, 23 Jun 2008 00:00:00 -0700

When doctors were recently asked which commonly prescribed medications they would avoid, they came up with the following eight. Perhaps you might want to reconsider these medications as well. At a minimum, speak to your doctor, as there are safer options for all of these medications.

Advair: This asthma medication contains the long-acting beta-agonist (LABA) salmeterol. A 2006 study of 19 trials, which was published in the Annals of Internal Medicine, revealed that with regular use, LABAs can increase asthma attack severity. Salmeterol is more widely prescribed than other LABAs, thus the danger is greater and may contribute to as many as 5,000 asthma-related deaths in the United States annually. Another study that same year led the US Food and Drug Administration (FDA) to label Advair with a "black box,” the FDA’s strongest warning.
Avandia: In September, the Journal of the American Medical Association (JAMA) revealed in a study that those taking diabetes drug Avandia—or rosiglitazone—for at least one year suffered an increased risk of heart failure (109 percent) or a heart attack (42 percent). One possible reason is that Avandia may cause dangerous fluid retention or raise artery-clogging LDL cholesterol. The FDA asked Avandia maker, GlaxoSmithKline, to conduct a long-term study assessing users' heart risks; however, that study is not expected to commence until later this year.
Celebrex: This pain medication is linked to increased risks of stomach bleeding, kidney trouble, and liver damage. According to a 2005 New England Journal of Medicine study people taking 200 mg of Celebrex twice daily more than doubled their risk of dying of cardiovascular disease; those on 400 mg twice daily more than tripled their risk. By the way, two other drugs in this drug class—Bextra and Vioxx--were banned for similar heart damage risks, yet Celebrex remains available.
Ketek: This antibiotic, generally prescribed for respiratory-tract infections, carries a higher risk of severe liver side effects, has been linked to heart-rhythm problems and liver disease, and can interact with other medications. Although still prescribed, the FDA limited Ketek’s usage to the treatment of pneumonia early last year.
Prilosec and Nexium: The FDA has investigated a suspected link between cardiac trouble and acid-reflux drugs Prilosec and Nexium. Also, because both drugs are proton-pump inhibitors, they may be overly effective at stopping stomach acid production, raising pneumonia, bone loss risk, and fracture risk (this, by over 40 percent in patients on long-term use).
Original Visine: Because Visine shrinks ocular blood vessels in the same way Afrin does nasally, overuse of its active ingredient tetrahydrozoline can create an endless loop of vessel dilating-and-constricting that may cause more redness, increasing the need for more Visine, causing more redness, and so on.
Pseudoephedrine: Other than that this decongestant is a critical component in methamphetamine, it can raise blood pressure and heart rate, has been linked to heart attacks and strokes, and can increase symptoms of benign prostate disease and glaucoma.

Outgoing Glaxo Head Says Drugs Should be Tested Sooner, Better

Tue, 20 May 2008 00:00:00 -0700

Outgoing head of GlaxoSmithKline (GSK) Jean-Pierre Garnier says the he does not foresee the US Food and Drug Administration (FDA) softening its position on drug approvals. Garnier is stepping down at the company’s annual meeting next week. “This is not a pendulum,” he says, “society wants to avoid risk. We have to tease out rare side effects earlier.”

Garnier added that the FDA has raised the bar and companies must adapt by shifting drug development priorities and conducting trials on targeted sub-populations to better realize rare side effects prior to regulatory submission. Other senior industry personnel suggest the U.S. election has strongly impacted the FDA’s position on new drugs and Garnier believes “the market will get reconstituted” with a new focus on so-called “progressive blockbusters,” which will ultimately reduce drug development costs by eliminating false negative results sooner.

But with the Pharmaceutical Price Regulation Scheme re-negotiations still ongoing in the United Kingdom, where GSK is based, and warnings of a shift away from the country for pharma research and development, Garnier says, “We want to compete on the basis of innovation. The translation of policies has to take account of those needs. As long as they do, we’ll be very happy to continue to stay … but you cannot handicap us."

Garnier, who will assume another healthcare role after he steps down as chief executive next week confessed to the Financial Times that there are things he wishes he had done differently, including earlier release of data for GSK’s beleaguered diabetes drug Avandia (rosiglitazone), but that overall he has “no regrets.”

In April, the FDA issued a warning to GlaxoSmithKline for not reporting safety results on Avandia. Avandia received the prominent, “Black Box” warning label last year and the FDA said that between 2001 and 2007 GlaxoSmithKline neglected to update the agency on over 10 ongoing studies of Avandia, as required by regulations. The FDA acknowledges that information from those studies was included and disclosed in other notices to the government; however, the FDA categorizes the omissions as “serious,” saying that the omissions “may be symptomatic of underlying post-market reporting failures.”

Last November, Avandia received a Black Box warning, which is the most serious labeling warning that a drug can carry. Black Box warnings are posted on medications as a means to alert doctors and patients that the drug could increase the risk of heart attacks, although in the case of Avandia, that evidence is currently not conclusive. The labeling change to the Black Box followed several high-profile congressional hearings where the FDA and Glaxo were criticized for not disclosing the drug’s potential risks earlier. A spokeswoman for Glaxo said the FDA had all safety studies on Avandia before it added the Black Box warning last year, adding that Glaxo is working with the FDA to resolve the issues.

Glaxo agreed to the FDA’s demand for a major study that will directly review Avandia’s heart effects. The study is not expected to be complete until 2014.

FDA Planning Hiring Blitz

Thu, 01 May 2008 00:00:00 -0700

The beleaguered Food & Drug Administration (FDA) is planning on filling over 1,300 positions by the end of September, triple the amount hired by the FDA over the past two years. The FDA will add 600 new jobs—including chemists, biologists, and statisticians—and will fill over 700 currently open posts. Most of the new positions will be in the department charged with reviewing new drugs; 150 will be in field offices that inspect manufacturing plants and food centers. The FDA currently has 10,000 employees.

Approximately 500 of the new positions will be funded by user fees paid to the FDA by drug makers filing applications to market new products, according to Christopher Kelly, FDA spokesman. These fees were appropriated from Congress as part of legislation passed in September that renewed and increased fees paid to the FDA by makers of drugs and medical devices, Kelly said. The FDA will hold recruitment fairs and conferences to fill the positions and most of the jobs will be at the FDA’s new headquarters in White Oak, Maryland.

The FDA has recently been under intense Congressional scrutiny due to the tragedies linked to the contaminated blood thinner heparin, tainted pet food, and the recall of Merck & Co.'s painkiller Vioxx. Earlier this year, Representative Bart Stupak said that if Americans "knew how little the FDA did to assure the food and drug supply, if the truth ever came out...people would be marching in the street." Stupak—an eight-term Democratic congressman and chairman of the Subcommittee on Oversight and Investigations of the House's powerful Energy and Commerce panel, which has jurisdiction over the FDA—is at the center of an aggressive effort by congressional Democrats to spotlight what they say are problems with the Bush administration's position on consumer-safety issues. Stupak called for the resignation of von Eschenbach and other top officials.

Representative John D. Dingell, Democrat-Michigan and chairman of the House Energy and Commerce Committee, has long been unhappy with the U.S. Food and Drug Administration (FDA) and its commissioner, Andrew von Eschenbach. Dingell recently accused von Eschenbach of not doing his job and has repeatedly asked the FDA chief how much it would cost to do more inspections. The commissioner still has not provided specifics.

Dingell and other lawmakers said the FDA must conduct more inspections of companies sending drugs to the U.S. to ensure they are safe. “You cannot do your job, you are not doing your job,'' Dingell told von Eschenbach, who was a witness at the hearing before the energy and commerce panel's investigations subcommittee. “You simply are absolutely incapable of addressing your responsibilities.''

Another Study Confirms Avandia, Actos Bone Fracture Risk

Tue, 29 Apr 2008 00:00:00 -0700

Avandia, a diabetes drug already mired in controversy, may double the risk of bone fractures, according to a new study. The study, conducted by Swiss researchers, found a similar risk with the diabetes drug Actos. Previous studies have found that these drugs increase the risk of bone fractures, but the Swiss study sheds light on how serious this problem might be.

Avandia has been a subject of debate since last May, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. Last July, the Food & Drug Administration (FDA) convened a panel to discuss the issues surrounding Avandia’s heart attack risk. The panel voted 20-3 that the drug did in fact raise the chance of heart attacks, yet the panel still voted 22-1 to allow it to remain on the market. In November, the FDA announced the addition of a long-awaited black box warning for Avandia’s increased risk of heart attacks. However, many patient advocates and FDA critics thought the black box warning was a weak response to Avandia’s safety issues. These critics continue to call on both GlaxoSmithKline, the maker of Avandia, and the FDA to pull the drug from the market. One diabetes expert, Dr. John Buse, has said that in action on Avandia might be responsible for as many as 83,000 preventable heart attacks.

According to the Swiss bone fracture study, those on Avandia or Actos had double or triple the odds of non-spine fractures. The odds for fracture were increased among patients who took the drugs for approximately 12 to 18 months and the risk was highest for those with two or more years of therapy. The researchers came to their conclusions by comparing the records of 1,020 diabetic patients with fractures diagnosed by British doctors between 1994 and 2005 against a control group of diabetics who did not have fractures.

Avandia and Actos belong to a class of medicines called thiazolidinediones. Last December, researchers in California published a study that explained the possible reasons for the drugs' effects on bone health. In the body, old bone cells are constantly being replaced by newer cells. This process helps to keep bones strong and resistant to fractures. While it was already known that thiazolidinediones inhibited the action of osteoblasts, cells in the body that build bone, the new research found that thiazolidinediones also appears to affect a key cellular protein called the peroxisome proliferator-activated receptor (PPAR-gamma). In their study, the California team discovered that activating this receptor in mice also stimulates the production of osteoclasts, cells whose key function is to degrade bone. Proper bone health is maintained by a balance between osteoclasts and osteoblasts. When this balance is upset, a patient becomes more susceptible to bone fractures, and stands a much higher chance of developing osteoporosis.

With an estimated 3.5 million or more U.S. patients taking thiazolidinediones, the public health impact from bone degradation could be substantial. Based on both the Swiss and California studies, diabetes patients already at a high risk for bone fractures and osteoporosis - for example, post-menopausal women - might want to ask their doctors about alternatives to thiazolidinediones. There are currently many diabetes drugs on the market that do not carry a similar bone fracture and osteoporosis risk.

FDA Considering Biomarkers As a Way to Improve Drug Safety

Thu, 17 Apr 2008 00:00:00 -0700

A new way of testing experimental drugs is being considered by the Food & Drug Administration (FDA). If adopted, the FDA could end up requiring "biomarker" tests for all new drugs. Proponents of the new biomarker process say it would help bring new drugs to market more quickly, while at the same time, reduce the risk that patients might be exposed to dangerous side effects that aren't apparent when new drugs are tested in animals. However, some patient advocates, while favoring the adoption of biomarker tests, say they will only be useful if drug makers take their results seriously. In the past, several high profile drugs - for example Avandia and Vytorin - showed signs of toxicity in animal tests. But those problems were ignored and the drugs proceeded to human clinical trials, and were eventually approved by the FDA.

A biomarker is an indicator that can be used to test a biological function. Some biomarkers turn up when organs are injured and cells within the damaged tissue release substances into the blood, urine or saliva. These substances can be used to detect dangerous side effects. Right now, the FDA is considering a testing process that uses seven indicators - known as biomarkers - that signal kidney injury when found in the urine of test subjects. Initially, the seven biomarker testing processes will be qualified by the FDA for use in preclinical animal studies, and only as a complement to current tests. But ultimately, the pharmaceutical industry would like to see the FDA adopt a range of such biomarker tests for human clinical trials that would signal dangerous side effects like heart failure, liver damage or cancer.

Under current testing protocols, experimental drugs are subjected to animal testing before they can move on to human clinical trials. But animal tests aren't always the best predictor of whether substances will be safe for humans. For example, if a drug toxic to the kidneys passes animal tests today, the damage might not show up until it is too late. Under a biomarker protocol, samples of blood, urine or saliva, would be taken from participants in a clinical trial. If certain biomarkers indicated the patient was at risk, the trial could be stopped before any major damage occurs.

It is hoped that biomarkers will speed the development of new drugs. Over the past 10 years, the number of new drugs and therapies submitted for FDA approval dropped by 50 percent. The move towards biomarkers has also been spurred by safety scandals surrounding some drugs, such as Vioxx, which was found to put users at risk for heart attacks and strokes after it came on the market.

While many patient advocates agree that biomarkers could go a long way towards improving drug safety, they contend the process will only work if drug makers abide by results. And some are skeptical that this will always be the case. Dr. Sidney Wolf of the group Public Citizen told the "San Francisco Chronicle" that in the past, drug makers have ignored safety issues apparent in early testing of drugs. "Findings of toxicity in the currently required animal tests are not taken seriously enough by companies or by the FDA," Wolfe said. "Avandia showed evidence of heart damage in animal studies and, for Vytorin, tests showed serious toxicity in laboratory animals, regardless of how low a dose of this combination drug was used." Both drugs came under fire in the last year because of problems, and the companies that developed them have been accused of withholding or downplaying vital information on safety and effectiveness when they were submitted to the FDA for approval.

Unfortunately, it is not unusual for drug makers to use the control they have over drug clinical trials to downplay disturbing findings. Yesterday, two reports in the “Journal of the American Medical Association” (JAMA) found Merck Inc. concealed mortality risks in two key Vioxx studies, and hired “ghostwriters” to author research that was supposedly conducted by independent scientists. Such practices are used throughout the drug industry, though they are hard to document, the authors of the JAMA reports said. Considering this history, it is fair to question whether or not the pharmaceutical companies would attempt to manipulate biomarker tests in the same way.

FDA Reprimands Glaxo for Avandia Study

Tue, 08 Apr 2008 00:00:00 -0700

The US Food and Drug Administration Federal (FDA) has just issued a warning to the drug maker, GlaxoSmithKline, for not reporting safety results on its diabetes pill Avandia. Avandia received the prominent, “Black Box” warning label last year and the FDA said that between 2001 and 2007 GlaxoSmithKline neglected to update the agency on over 10 ongoing studies of Avandia, as required by regulations. The FDA acknowledges that information from those studies were included and disclosed in other notices to the government; however, the FDA categorizes the omissions as “serious,” saying that the omissions “may be symptomatic of underlying post-market reporting failures.”

Last November, Avandia received a Black Box warning, which is the most serious labeling warning that a drug can carry. A Black Box warning was posted on the medication as a means to alert doctors and patients that Avandia could increase the risk of heart attacks. The labeling change to the Black Box followed several high-profile congressional hearings where FDA and Glaxo were criticized for not disclosing the drug’s potential risks earlier. Today, a spokeswoman for Glaxo said the FDA had all safety studies on Avandia before it added the Black Box warning last year, adding that Glaxo is working with the FDA to resolve the issues.

Glaxo has agreed to the FDA’s demand for a major study that will directly review Avandia’s heart effects. The study is not expected to be complete until 2014.

Meanwhile, lawsuits against GlaxoSmithKline over Avandia are emerging and many more lawsuits are expected to be filed. One man is suing GlaxoSmithKline in federal court, claiming Avandia caused him to have to undergo heart bypass surgery. Attorneys allege that the drug maker should have known that Avandia—which is prescribed to improve blood sugar in type 2 diabetes patients—is linked to a significant and increased risk of heart failure, heart attack, and stroke.

The FDA refuses to withdraw Avandia from the market, but has asked Glaxo to conduct the long-term study that will compare Avandia with other type 2 diabetes drugs. The trial will likely commence in a year; however, it will be years before the study is complete and the results are made available. Patient advocates and FDA critics consider the recent Black Box warning for Avandia to be a feeble response to Avandia’s ongoing safety issues, requesting that Avandia be pulled from the market. Meanwhile, the American Diabetes Association and the European Association for the Study of Diabetes recently released a revised consensus statement that stated that the emerging information suggests that there are additional hazards associated with Avandia and that the drug may result in increased risk of myocardial infarctions. The US Department of Veterans Affairs also recently announced that it was dropping Avandia from its drug formulary because, in some, Avandia did not afford the same margin of safety as some other diabetes drugs. A Congressional Committee Report also found that Glaxo executives had intimidated a diabetes expert into keeping quiet about Avandia’s safety problems.

More Heat for Vytorin and Avandia

Wed, 05 Mar 2008 00:00:00 -0800

Avandia and Vytorin are the subject of yet another government investigation. The Government Accountability Office (GAO) will look into whether the US Food and Drug Administration’s (FDA) drug-review process cleared two popular medications without sufficient proof of their safety or effectiveness.

Senator Charles E. Grassley (Republican-Iowa) requested the GAO investigation after recent studies suggested that the diabetes pill Avandia increases the risk of cardiac problems in patients, and another study showed that the cholesterol drug Vytorin may not actually lower the risk of heart attack and artery-clogging plaque, as assumed by millions of patients and doctors. "There's enough of a pattern of problematic drugs to ask for an independent review of how the FDA follows up on the effects of medicines that it's approved," Grassley said. The question is whether the FDA should approve drugs based on biological measures, such as cholesterol and blood sugar, without evidence that they improve more meaningful measures, such as survival.

The makers of Vytorin have been named as defendants in a lawsuit filed by a New York man who took the defective drug based on the belief that it offered more protection from clogged arteries, heart attacks and strokes than other, less expensive statin drugs. Sigmond Tomaszewski, who began taking Vytorin in January 2007, alleges that Merck and Schering-Plough knew in April 2006 that Vytorin was ineffective at reducing artery clogging plaque, heart attacks and strokes, but purposely kept that information from the public and the medical community.

Lawsuits against GlaxoSmithKline over the diabetes drug Avandia are emerging and many more are expected. One a man is suing GlaxoSmithKline in federal court, claiming Avandia caused him to undergo heart bypass surgery. Attorneys allege the drug maker should have known that Avandia—prescribed to improve blood sugar in type 2 diabetes patients—is linked to a significant and increased risk of heart failure, heart attack, and stroke.

The FDA refuses to withdraw Avandia from the market, but has asked Glaxo to conduct a long-term study comparing Avandia with other type 2 diabetes drugs. The trial will likely commence in a year; however, full results are not expected until 2014. Patient advocates and FDA critics consider the recent black box warning—the strongest warning for a drug—for Avandia a feeble response to Avandia’s safety issues, and have requested it be pulled from the market. Meanwhile, the American Diabetes Association and the European Association for the Study of Diabetes released a revised consensus statement stating that emerging information suggests additional hazards associated Avandia and may result in increased risk of myocardial infarctions. The US Department of Veterans Affairs announced it was dropping Avandia from its drug formulary because, in some, Avandia did not afford the same margin of safety as other diabetes drugs. A Congressional Committee Report found Glaxo executives intimidated a diabetes expert into
keeping quiet about Avandia’s safety problems.

Avandia Woes Mean Cutbacks at GlaxoSmithKline

Tue, 19 Feb 2008 00:00:00 -0800

Avandia problems continue to hurt GlaxoSmithKline’s bottom line, as the Avandia maker announced this week that it would be giving up more than a $1 million in incentives so that it could eliminate jobs at its Zebulon, NC manufacturing plant. Avandia sales have dropped more than $1 billion worldwide since the controversial diabetes drug was linked to cardiac problems last may. The possible job cuts at the Zebulon plant are part of Glaxo’s plan to stem the bleeding caused by the Avandia debacle, as well as regulatory delays of some drugs awaiting approval and growing generic competition for some its other best selling medications.

Earlier this month, Glaxo announced that its fourth-quarter net income plunged 10 percent as sales of the Avandia diabetes pill decreased by more than half in the U.S. That news caused the price of Glaxo stock to drop to its lowest level in six years. Glaxo revenues also fell because two of its medications, Coreg for high blood pressure and antidepressant Wellbutrin, lost patent protection and now face generic competition. Glaxo also failed to get its most-promising new product, the Cervarix cervical cancer vaccine, approved in the U.S.

The incentives that Glaxo is giving up in North Carolina would have amounted to $1.4 million. The incentives were part of an agreement with the state that required Glaxo to invest at least $92 million in the Zebulon plant and create 200 jobs by the end of 2009. On Thursday, a state committee accepted Glaxo’s request to terminate the agreement effective Feb. 23. At the Zebulon plant, temporary workers and contractors have been let go and vacancies are not being filled. Glaxo has said layoffs at the plant could come soon. Zebulon is one of Glaxo's largest production plants. Twenty-three medicines are made or packaged for the U.S. market at the plant. With a work force of about 1,000, it is one of the largest employers in the North Carolina town.

Glaxo has also notified an undisclosed number of workers at its U.S. headquarters in North Carolina’s Research Triangle Park that their jobs will be eliminated. The company employs about 6,000 people there.

Avandia has been a subject of controversy since May 2007, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. In June 2007, Congress held hearings to discuss Avandia and the Food & Drug Administration’s (FDA) handling of its safety issues. At those hearings, it was revealed that in 2005 GlaxoSmithKline had informed the FDA of a study it had conducted that produced similar results. However, both the agency and the manufacturer felt that more investigation was needed before conclusions could be made about Avandia’s possible safety issues. Thus, the public was not made aware of the Avandia heart attack risk until the publication of the Cleveland Clinic article.

First Avandia Lawsuits Filed, Many More Expected

Mon, 18 Feb 2008 00:00:00 -0800

Avandia lawsuits against GlaxoSmithKline over the drugs alleged cardiac side effects are beginning to make their way through the courts, and many more are expected. One a man is suing GlaxoSmithKline in federal court, claiming Avandia caused him to undergo heart bypass surgery. Attorneys allege the drug maker should have known that Avandia—prescribed to improve blood sugar in type 2 diabetes patients—is linked to a significant and increased risk of heart failure, heart attack, and stroke.

The lawsuit is among several filed nationwide targeting Avandia and Glaxo; it is believed there are thousands yet to be filed. Over six million Americans used the drug and concern about Avandia is nothing new. The connection between Avandia and increased heart failure risk has been known since 1999 when the drug was first approved.   Avandia sales have plummeted since publication in The New England Journal of Medicine linking Avandia with increased risk of heart attack and failure, but Nancy Pekarek, spokeswoman for GlaxoSmithKline, said the company stands by Avandia, "We are certainly confident that when the courts or the juries look at the clinical data, the responsible way in which we communicated that information, and our openness in posting our clinical trial data online, they will see our position," she said. The lawsuit alleges that the company "had the knowledge, the means, and the duty to provide the medical community and the consuming public with more accurate descriptive information and more ade
quate warnings regarding the association between Avandia and heart failure...”

Pat Kelly, 59, said he took Avandia led to painful heart trouble and heart bypass surgery in 2007. Kelly had over 40 years in the auction business and frequently traveled nationwide for his work, but says he has no energy and no jobs. "To put it bluntly, I went from a hero to a zero. I simply don't have the energy that I did. I don't have the stamina I did," he said. “My God, how many other people has (the drug) touched?" Kelly wonders.   Avandia breaks down the body's resistance to insulin but has long been known to cause fluid retention, a major risk factor for congestive heart failure.

The Food & Drug Administration (FDA) refuses to withdraw Avandia from the market, but has asked Glaxo to conduct a long-term study comparing Avandia with other type 2 diabetes drugs. The trial will likely commence in a year; however, full results are not expected until 2014. Patient advocates and FDA critics consider the recent black box warning—the strongest warning for a drug—for Avandia a feeble response to Avandia’s safety issues, requesting it be pulled from the market. Meanwhile, the American Diabetes Association and the European Association for the Study of Diabetes released a revised consensus statement stating that emerging information suggests additional hazards associated Avandia and may result in increased risk of myocardial infarctions. The US Department of Veterans Affairs announced it was dropping Avandia from its drug formulary because, in some, Avandia did not afford the same margin of safety as other diabetes drugs.   A Congressional Committee Report found Glaxo executives intimidated a diabetes expert into keeping quiet about Avandia’s safety problems.

Avandia Study Leaked by Glaxo-Paid Reviewer

Thu, 31 Jan 2008 00:00:00 -0800

The Avandia study that touched off a firestorm over the diabetes drug’s cardiac side effects was leaked to GlaxoSmithKline ahead of its publication in the New England Journal of Medicine (NEJM). According to a report in the Wall Street Journal, a physician who was helping peer-review the Avandia article broke NEJM confidentiality rules and faxed a copy of the article to Glaxo 17 days before it was published. The physician who leaked the study has received substantial speaking and consulting fees from Glaxo, and now one law maker wants to know if this relationship played a role in the Avandia study leak.

Avandia has been a subject of controversy since May 2007, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. In June 2007, Congress held hearings to discuss Avandia and the Food & Drug Administration's (FDA) handling of its safety issues. At those hearings, it was revealed that in 2005 GlaxoSmithKline had informed the FDA of a study it had conducted that produced similar results. However, both the agency and the manufacturer felt that more investigation was needed before conclusions could be made about Avandia’s possible safety issues. Thus, the public was not made aware of the Avandia heart attack risk until the publication of the Cleveland Clinic article

It was that article that Steven Haffner, a physician at the University of Texas Health Science Center at San Antonio admittedly leaked to Glaxo. Haffner faxed a copy of the study 17 days before it was published to Alexander Cobitz, a Glaxo employee he knew from working on an earlier clinical trial of the drug.

Haffner was one of those asked by the journal to "peer-review" the Cleveland Clinic Avandia study.   Major medical and scientific journals subject the studies they publish to this process, under which experts in the field assess the validity of a study’s conclusions. Peer reviewers promise to keep the research confidential until it is published.

Haffner told the journal “Nature” that he does not know why he chose to break the rules and forward the study to Glaxo, and called his conduct “bad judgment.”   Whatever the reason, Glaxo used the advanced warning of the study to prepare its response to the Avandia scandal.

The news of the Avandia study leak has one Congressman asking questions. Senator Charles Grassley (R-Iowa), a ranking member of the Senate Finance Committee has written Glaxo, asking for more information on the breach of confidentiality, as well as payments Haffner received from the drug maker.

"According to documents filed at the FDA, GSK has paid Dr. Haffner around $75,000 in consulting fees and speaking honoraria since 1999. Dr. Haffner told Committee investigators that no one at GSK asked him to send them this study about Avandia," Grassley wrote. "Nonetheless, I am interested in what GSK did after receiving the study. Did GSK return the study to Dr. Haffner? Did GSK contact the NEJM to report this violation of publishing ethics?"

Haffner told “Nature” that "I didn't do it to raise my income or anything like that.”   But without a better explanation for his conduct, the Avandia leak will only raise more questions about the conflicts-of –interest created by drug company payments to scientists involved in drug research.

Avandia Defects Could be Responsible for 83,000 Excess Heart Attacks

Thu, 10 Jan 2008 00:00:00 -0800

Avandia could have been responsible for an additional 83,000 heart attacks. That stunning number comes from an Avandia analysis performed by Food & Drug Administration (FDA) scientists presented at a July 2007 safety panel meeting.   The Avandia heart attack analysis is included in a report released in November by the Senate Finance Committee entitled “The Intimidation of Dr. John Buse and the Diabetes Drug Avandia.”

Avandia’s heart attack link came to light when an analysis of 42 clinical trails published by the Cleveland Clinic in May showed that patients taking the drug had a 43% higher risk of having a heart attack. Late last year, the FDA announced the addition of a long-awaited black box warning for Avandia’s increased risk of heart attacks. However, many patient advocates and FDA critics thought the black box warning was a weak response to Avandia’s safety issues, and have called on GlaxoSmithKline, the maker of Avandia, and the FDA to pull the drug from the market.

The Avandia debacle has shed a great deal of light on the uncomfortable relationship between the FDA and drug makers like Glaxo. At July Senate hearings on Avandia, it was revealed that Glaxo had informed the FDA of a study it had conducted that produced results similar to the Cleveland Clinic study. However, both the agency and the manufacturer felt that more investigation was needed before conclusions could be made about Avandia’s possible safety issues. The FDA also spent months negotiating with Glaxo over Avandia’s black box heart attack warning, and some consumer advocates argue that the warning is too weak as a result.

Now it appears Glaxo might have tried intimidation to silence one Avandia critic.   Dr Buse is an expert in diabetes with extensive research experience in the thiazolidinedione class of drugs that includes Avandia.   In 1999, Dr. Buse began expressing concerns about the cardiovascular risks of Avandia.   Earlier this summer, the Senate committee heard testimony from Dr. Buse, who said he felt pressured by the drug’s maker, SmithKlineBeecham (now part of GlaxoSmithKline) to sign a clarifying statement drafted by the company that downplayed his concerns. During his testimony, Dr. Buse described name-calling and what he said was the veiled threat of a lawsuit by a high-ranking drug company executive after he had criticized Avandia at a medical meeting. Dr. Buse also testified that Glaxo complained about him to his supervisors at the University of North Carolina.

Now, the Senate Committee has implicated two high-ranking Glaxo executives in the intimidation campaign against Dr. Buse. The report alleges that Glaxo Chief Executive Jean-Pierre Garnier and former research chief Tachi Yamada were involved in the intimidation.   Dr. Buse had also named Yamada in testimony to the Senate committee. The report cites several emails as evidence of this intimidation, including one that says in part “ …write him a firm letter that would warn him about doing this again…with the punishment being that we will complain up his academic line and to the CME granting bodies that accredit his activities….The question comes up as to whether you think this is a sensible strategy in the future (we don’t really do too much work at UNC to make any threats).”

According to the Senate Committee report, if Glaxo had considered Avandia’s increased cardiovascular risk more seriously when the issue was first raised in 1999 by Dr Buse, “instead of trying to smother an independent medical opinion,” some 83,000 Avandia heart attacks may have been avoided.

Despite the evidence of intimidation included in the Senate Committee report, Glaxo insists the allegations are false.

GlaxoSmithKline, AstraZeneca at Center of Iraq Bribe Probe in Britain

Wed, 02 Jan 2008 00:00:00 -0800

GlaxoSmthKline, the maker of Avandia, and AstraZeneca, another large drug maker, are being investigated in Britain for allegedly bribing the regime of Saddam Hussein in Iraq. The revelation of the UK bribe probe is bad news for both companies, but it especially ominous for Glaxo. Glaxo has been sullied by the safety scandal surrounding its diabetes drug Avandia, and sales of the drug have fallen, causing considerable damage to Glaxo’s bottom line.

Glaxo is still trying to recover from its Avandia problems, and hardly needs the bad publicity of a bribery probe. Avandia has been a subject of debate since May 21, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. Since the Cleveland Clinic study was published, a great deal of controversy has swirled around Avandia. In June, Congress held hearings to discuss Avandia and the Food & Drug Administration's (FDA) handling of its safety issues. At those hearings, it was revealed that Glaxo had informed the FDA of a study it had conducted that produced results similar to the Cleveland Clinic study. However, both the agency and the manufacturer felt that more investigation was needed before conclusions could be made about Avandia’s possible safety issues. As a result, the Avandia heart attack risk was not publicized until May 2007. A black box warning about heart problems was finally added to the Avandia label in November, but since the scandal broke, Avandia sales have fallen considerably, and several large insurers have stopped paying for the drug.

According to the Wall Street Journal, The UK's Serious Fraud Office began its probe in February, when it started looking into possible breaches of the United Nations' oil-for-food program. The program was designed to allow the government of Iraq, which was facing international sanctions, to sell oil to meet humanitarian needs. The investigation was triggered by an audit for the U.N. of the program in 2005 by Paul Volcker, former chairman of the US Federal Reserve. Glaxo and AstraZeneca have been asked to give documents to the Serious Fraud Office as part of the probe.

Glaxo and AstraZeneca said they were cooperating fully with the inquiry, but denied wrongdoing. Glaxo said in a statement that it went to “great lengths impose anticorruption measures when dealing with intermediaries in Iraq at a time when the environment was extremely volatile and difficult." For its part, AstraZeneca said it had sent a consignment of medicines to Iraq under the oil-for-food program but denied "any allegation of unethical behavior on our part in our trading relationships with Iraq." It said all drugs were sent with proper U.N. and U.K. documentation.

Avandia Heart Attacks, Other Cardiac Problems Now Being Seen in General Patient Population

Mon, 17 Dec 2007 00:00:00 -0800

The consequences of deadly Avandia side-effects are now being seen in the general population, a new study has found. Previously, evidence that Avandia placed patients at an increased risk of heart attacks had only been seen in clinical trials. But now, Canadian researchers have found that patients taking the controversial diabetes drug who are not enrolled in clinical trials are showing increased evidence of heart attacks and other cardiac problems.

Avandia’s heart attack link came to light when an analysis of 42 clinical trails published by the Cleveland Clinic in May showed that patients taking the drug had a 43% higher risk of having a heart attack. Just last month, the Food & Drug Administration (FDA) announced the addition of a long-awaited black box warning for Avandia’s increased risk of heart attacks. However, many patient advocates and FDA critics thought the black box warning was a weak response to Avandia’s safety issues, and have called on GlaxoSmithKline, the maker of Avandia, and the FDA to pull the drug from the market.

Now, it seems that Avandia side effects have reached the general public. That is made clear in a study conducted by scientists at the Institute for Clinical Evaluative Sciences in Toronto, Canada. Researchers there analyzed data for 159,026 older adults who were treated with at least one oral diabetes drug between 2002 and 2005 and were entered in an Ontario healthcare database. The subjects were followed through March 2006. During an average follow-up period of 3.8 years, 7.9 percent of the patients were hospitalized for congestive heart failure, 7.9 percent were hospitalized for a heart attack, and 19 percent died, according to the researchers' report in Journal of the American Medical Association. Further analysis revealed that the risks were largely confined to patients who were using Avandia, known generically as rosiglitazone.

The Canadian researchers wrote that their findings "provide evidence from a real-world setting and support data from clinical trials that the harms of thiazolidinediones may outweigh their benefits, even in patients without obvious...cardiovascular disease".

This latest research does not bode well for Avandia. Earlier this month, pharmacy benefit managers HealthTrans and Prime Therapeutics announced that they would be dropping the controversial diabetes drug from their value-based prescription drug formularies as of January 1, 2008 because of safety concerns. In October, the Department of Veterans Affairs (VA) announced that it was removing Avandia from its prescription drug formulary because of its heart attack risks. The VA said that it would still make Avandia available for patients who were already taking it and wanted to continue. But the decision means that patients not currently prescribed Avandia will not be able to get it through the VA in the future. Prior to its announcement, the VA accounted for about 8 percent of Avandia sales.

Avandia was once GlaxoSmithKline’s second-biggest selling drug, with worldwide revenue of $3.2 billion in 2006, but sales have plunged since May, with US sales down 48 percent in the third quarter from a year ago.

Older Avandia Patients Have Higher Rates of Heart Attacks, Death

Wed, 12 Dec 2007 00:00:00 -0800

Avandia puts older patients at a significantly higher risk of heart attack and death, says a new study.   The research, conducted by the Institute for Clinical Evaluative Sciences in Toronto, Canada, is just the latest scientific evidence to highlight Avandia’s safety issues. Only last month, a black box warning detailing Avandia’s heart attack risks was added to the label of the controversial diabetes drug, but that move has done little to quiet critics who believe Avandia should be pulled from the market.

Avandia has been a subject of debate since May 21, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. This latest Avandia study, published in the “Journal of the American Medical Association” analyzed drug use and health outcomes for 159,000 people age 65 and older treated for Type 2 diabetes in Ontario, Canada. Of those patients, 2,268 people where being treated with Avandia.   The analysis found that for every 100 people taking Avandia over a four-year period there would be five additional deaths, four additional heart attacks and three additional episodes of heart failure.

Dr. Steven Nissen, who headed the Cleveland Clinic Avandia study, told The New York Times that the Canadian research mirrored his findings, and said that they should prompt the Food & Drug Administration (FDA) to take another look at Avandia. “As you accumulate more and more evidence that Avandia has this problem, and it involves a very serious consequence, namely heart attack and death, it puts a lot of pressure on the FDA to do more,” Dr. Nissan said.

But at this time, the FDA does not seem inclined to act on the findings of the latest Avandia study. In a statement released yesterday, the agency said that the Canadian research would not change its recommendations on Avandia. “The information FDA provided for the most recent labeling change remains accurate — the data are inconclusive and we have added a boxed warning to the labeling to ensure that health care professionals and patients are aware of this potential risk and can take this into account as they make individual prescribing decisions,” the statement read.

The FDA’s stance will not surprise many Avandia critics, who feel the agency has been less than aggressive in dealing with the drug’s safety problems. Over the summer, GlaxoSmithKline, the maker of Avandia, and the FDA came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. Testimony at a congressional hearing in June revealed that the company and the FDA had known about the heart attack risk as far back as September 2005. That congressional investigation also uncovered allegations that in 2005, an FDA scientist who had advocated for a strong black box warning on Avandia about its risk for congestive heart failure had been removed from an Avandia safety review.

Even after Avandia’s heart attack risk became clearer, the FDA spent months negotiating with Glaxo over the wording of a black box warning.   The FDA’s decision last month to finally add a black box label to Avandia did little to quiet critics, who charged the wording was too weak. That black warning states that “the available data on the risk of myocardial ischemia are inconclusive.”

Avandia Removed from HealthTrans Pharmacy, Prime Therapeutics Formularies Due to Heart Attack Risk

Fri, 07 Dec 2007 00:00:00 -0800

Avandia has taken another hit on the chin, as two large pharmacy benefit managers announced that they would be dropping the controversial diabetes drug from their value-based prescription drug formularies as of January 1, 2008 because of safety concerns. The decision by HealthTrans Pharmacy and Prime Therapeutics to stop covering Avandia will do little to help sales of the drug, which have gone downhill since it was associated with an increased risk of heart attack in May.

Avandia's heart attack link came to light when an analysis of 42 clinical trails published by the Cleveland Clinic in May showed that patients taking the drug had a 43% higher risk of having a heart attack. Just last month, the Food & Drug Administration (FDA) announced the addition of a long-awaited black box warning for Avandia's increased risk of heart attacks. However, many patient advocates and FDA critics thought the black box warning was a weak response to Avandia's safety issues, and have called on GlaxoSmithKline, the maker of Avandia, and the FDA to pull the drug from the market.

In announcing their decisions, both HealthTrans and Prime Therapeutics said that the safety issues surrounding Avandia where the main reasons for the drug's removal from their formularies. "Our first concern is the safety of individuals taking medications included in our value-based formulary," Ryan Haynes, R.Ph., director of clinical services for HealthTrans said in a press release. "Our P&T committee analyzed available data and weighed the benefits with the potential risks and determined that Avandia presents a greater risk for adverse events than benefits at this time."

HealthTrans and Prime Therapeutics are just the latest healthcare providers to move to limit access to Avandia since issues surrounding its safety came to light. In October, the Department of Veterans Affairs (VA) announced that it was removing Avandia from its prescription drug formulary because of its heart attack risks. The VA said that it would still make Avandia available for patients who were already taking it and wanted to continue. But the decision means that patients not currently prescribed Avandia will not be able to get it through the VA in the future. Prior to its announcement, the VA accounted for about 8% of Avandia sales.

In late November, the American Diabetes Association announced that it was updating its "consensus statement" on the use of oral diabetes medications in light of the increased heart attack risks linked to some diabetes medicines, such as Avandia. The new consensus statement reads in part: "New information suggests additional hazards associated with the use of either thiazolidedione, and rosiglitazone (Avandia) in particular may result in an increased frequency of myocardial infarctions. . . We therefore recommend greater caution in using thiazolidediones, especially in patients at risk of, or with, congestive heart failure." The American Diabetes Association is one of the most influential diabetes groups in the US, and its recommendations carry a lot of weight with doctors.

Avandia was once GlaxoSmithKline's second-biggest selling drug, with worldwide revenue of $3.2 billion in 2006, but sales have plunged since May, with US sales down 48 percent in the third quarter from a year ago.

Avandia Researchers Find Reason Behind Bone Fracture, Osteoporosis Side Effects

Mon, 03 Dec 2007 00:00:00 -0800

Avandia places patients at a high risk of bone fractures and osteoporosis by affecting the way bone cells are replenished in the body. While bone fractures are a well known Avandia side effect, no one understood how the diabetes medication affected bone structure. Now, researchers at the Salk Institute for Biological Studies in La Jolla, California have discovered that Avandia affects the workings of two types of cells important to the process of replacing old bone. They surmise that Avandia's action on these cells, osteoblasts and osteoclasts, could account for the bone fracture risks faced by Avandia patients.

In the body, old bone cells are constantly being replaced by newer cells. This process helps to keep bones strong and resistant to fractures. But researchers studying the affects of Avandia on the bone structure of mice found that the medication interferes with this process in two important ways. While it was already known that Avandia inhibited the action of osteoblasts, cells in the body that build bone, the new research found that Avandia also appears to affect a key cellular protein called the peroxisome proliferator-activated receptor (PPAR-gamma). In their study, the California team discovered that activating this receptor in mice also stimulates the production of osteoclasts, cells whose key function is to degrade bone. Proper bone health is maintained by a balance between osteoclasts and osteoblasts. When this balance is upset, a patient becomes more susceptible to bone fractures, and stands a much higher chance of developing osteoporosis.

With an estimated 3.5 million or more U.S. patients taking Avandia, the public health impact from bone degradation could be substantial. Based on the California Avandia study, diabetes patients already at a high risk for bone fractures and osteoporosis - for example, post-menopausal women - might want to ask their doctors about alternatives to Avandia. There are currently many diabetes drugs on the market that do not carry the bone fracture and osteoporosis risk that Avandia does.

Avandia has been a subject of debate since May 21, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. In July, the Food & Drug Administration (FDA) convened a panel to discuss the issues surrounding Avandia's heart attack risk. The panel voted 20-3 that the drug did in fact raise the chance of heart attacks, yet the panel still voted 22-1 to allow it to remain on the market. In November, the FDA announced the addition of a long-awaited black box warning for Avandia's increased risk of heart attacks. However, many patient advocates and FDA critics thought the black box warning was a weak response to Avandia's safety issues. These critics continue to call on both GlaxoSmithKline, the maker of Avandia, and the FDA to pull the drug from the market.

Avandia Heart Attack Controversy Results in Black Box Warning, but Critics Still Want Diabetes Drug Off the Market

Thu, 29 Nov 2007 00:00:00 -0800

Avandia, a drug used in the treatment of type 2 diabetes, has been at the center of controversy since being linked to an increased risk of heart attack last May. An update to the black box warning-today's strongest drug warning-is now being added to the Avandia label. The U.S. Food and Drug Administration (FDA) advised that GlaxoSmithKline, Avandia's maker, agreed to add the new warning to the existing black box warning. But, despite the revision, the FDA will not withdraw Avandia from the market, claiming that evidence for increased heart attack is inconclusive and does not appear to be higher in Avandia than other type 2 diabetes treatments. In the meantime, the FDA asked GlaxoSmithKline to conduct a long-term study comparing Avandia with other type 2 diabetes drugs. The trial will likely commence in a year; however, full results will not be available until 2014. Patient advocates and FDA critics consider the black box warning a weak response to Avandia's safety issues and have requested Avandia be pulled from the market.

Avandia breaks down the body's resistance to insulin but has long been known to cause fluid retention, a major risk factor for congestive heart failure. Evidence does not indicate Avandia and other oral anti-diabetes drugs-thiazolidinediones-prevent cardiovascular risk as a result of reducing blood sugar.

The American Diabetes Association and the European Association for the Study of Diabetes released a revised consensus statement stating that emerging information suggests additional hazards associated with thiazolidedione and rosiglitazone (Avandia) and may result in increased risk of myocardial infarctions. In October, the US Department of Veterans Affairs (VA) announced it was dropping Avandia from its prescription drug formulary stating their review concluded that, in some, Avandia did not afford the same margin of safety as other diabetes medications. The VA accounted for nearly 10-percent of Avandia's US sales. In November, Health Canada sent a letter to Canadian health professionals advising Avandia could no longer be prescribed as monotherapy for type 2 diabetes or in combination with sulfonylurea. In May, research based on 42 Avandia studies confirmed a 43-percent increased risk of heart attack among patients taking the drug. In August, Avandia's warning label was changed to warn that Avandia and others in its class might worsen heart failure. A Congressional Committee Report found that company executives made a concerted effort to intimidate a diabetes expert into keeping quiet about Avandia's safety problems, alleging that Glaxo Chief Executive Jean-Pierre Garnier and former research chief Tachi Yamada were involved. An internal government memo dated July 16, 2002 analyzed 47 early FDA reports of patients who went into heart failure and required hospitalization while taking Avandia. The report contained warnings from Federal investigators that Avandia might cause heart failure.

Over six million Americans have used the drug to treat adult-onset, or type 2, diabetes and the concern about Avandia is nothing new. The association between Avandia and increased heart failure risk has been known since 1999 when the drug was first approved.

Avandia was Glaxo's second most popular drug in 2006, with sales of $3.3 billion. Sales have plummeted since publication of evidence linking Avandia with increased risk of heart attack and failure.

Avandia Side Effects Prompt New Caution from American Diabetes Association

Tue, 27 Nov 2007 00:00:00 -0800

Risks associated with Avandia have led the American Diabetes Association to call on doctors to use more caution when prescribing oral medications to treat people with type two diabetes. The Association announced on Tuesday that it was updating its "consensus statement" on the use of oral diabetes medications in light of the increased heart attack risks linked to some diabetes medicines, such as Avandia.

Avandia's heart attack link came to light in May, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43% higher risk of having a heart attack. Earlier this month, the Food & Drug Administration (FDA) announced the addition of a long-awaited black box warning for Avandia's increased risk of heart attacks. However, many patient advocates and FDA critics thought the black box warning was a weak response to Avandia's safety issues, and have called on both GlaxoSmithKline, the maker of Avandia, and the FDA to pull the drug from the market.

The American Diabetes Association's revised consensus statement was formulated in cooperation with European Association for the Study of Diabetes. The statement reads in part: "New information suggests additional hazards associated with the use of either thiazolidedione, and rosiglitazone (Avandia) in particular may result in an increased frequency of myocardial infarctions. . . We therefore recommend greater caution in using thiazolidediones, especially in patients at risk of, or with, congestive heart failure."

The American Diabetes Association's new Avandia stance is only the latest development that could hurt the drug's sagging sales. In October, the United States Department of Veterans Affairs (VA) announced that it was dropping Avandia from its prescription drug formulary. In a statement announcing the move, the VA said that it had conducted its own review and concluded that, for some patients, Avandia did not afford the same margin of safety as other diabetes medications. Prior to its announcement, the VA accounted for about 8% of Avandia's sales in the United States. And in November, Health Canada sent a letter to Canadian health professionals informing them that Avandia could no longer be prescribed as monotherapy for type 2 diabetes, except when metformin use is contraindicated or not tolerated. Health Canada also withdrew its approval for Avandia to be used in combination with a sulfonylurea, except when metformin is contraindicated or not tolerated.

Last week, Glaxo got more bad news on the Avandia front when a Congressional Committee Report found that company executives made a concerted effort to intimidate Dr. John Buse, a diabetes expert, into keeping quiet about some of the Avandia's safety problems. The report alleged that Glaxo Chief Executive Jean-Pierre Garnier and former research chief Tachi Yamada were involved in the intimidation.

Avandia was once Glaxo's second biggest selling drug, but sales in the US dropped 48% after the Cleveland Clinic published its heart attack study.

Avandia Reviewer Calls for Changes in FDA Drug Approval Process

Tue, 27 Nov 2007 00:00:00 -0800

The Avandia debacle has prompted a safety official from the Food & Drug Administration (FDA) to call for changes in the way diabetes medications are approved for use in the United States. The FDA official, who reviewed the original approval application for Avandia, told the Journal of Diabetes Care that the safety and effectiveness of experimental diabetes medications should be tested against existing drugs before they are approved. If such a testing protocol were to be adopted by the FDA, it would mark a significant departure from the way most medications are granted approval in the United States.

Avandia has been a subject of debate since May 21, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. Since the Cleveland Clinic study was published, a great deal of controversy has swirled around Avandia. In June, Congress held hearings to discuss Avandia and the FDA's handling of its safety issues. At those hearings, it was revealed that GlaxoSmithKline, Avandia's manufacturer, had informed the FDA of a study it had conducted that produced similar results. However, both the agency and the manufacturer felt that more investigation was needed before conclusions could be made about Avandia's possible safety issues. Since those revelations were made public, the FDA has been under a great deal of pressure to take action on Avandia.

In July, the FDA convened a panel to discuss the issues surrounding Avandia's heart attack risk. The panel voted 20-3 that the drug did in fact raise the chance of heart attacks, yet the panel still voted 22-1 to allow it to remain on the market. They recommended that Avandia be given a warning label about the cardiac problems. The FDA did finally add that black box warning to the Avandia label this month.

Now, Dr. Robert Misbin, an FDA safety reviewer who worked on the original Avandia approval, has called for changes in the way such drugs are handled by the FDA. Currently, an experimental drug is tested against a placebo. But Dr. Misbin now feels that diabetes drugs like Avandia, should be tested against other drugs currently on the market. In his interview with the Journal of Diabetic Care, Dr. Misbin likened comparing a drug's effectiveness to a placebo to evaluating it in a vacuum. Dr. Misbin argued that putting an experimental medication up against a tried and true existing drug would give medical reviewers a better idea of the new medication's efficacy and safety.

Dr. Misbin focused his comments on diabetes drugs, because he was part of the Avandia approval process, and because the subsequent safety issues surrounding Avandia highlighted weaknesses in the FDA approval system. Misbin also said because there are so many safe and effective diabetes medications on the market now, experimental diabetes drugs should have to pass more hurdles to be approved by the FDA.

Avandia Safety Scandal Won't Go Away, As Senators Seek to Question Former Glaxo Exec

Fri, 23 Nov 2007 00:00:00 -0800

The addition of a new Avandia black box warning about heart attack risk has done little to quell criticism over the way GlaxosmithKline, the drug’s manufacturer, and the Food & Drug Administration (FDA) handled concerns over Avandia safety. Earlier this week, a Senate Committee report found that Glaxo had engaged in a concerted effort to intimidate a leading diabetes doctor in order to force him to stay silent about his Avandia concerns. Now, two prominent senators are seeking to question a former Glaxo executive who was allegedly involved in that intimidation campaign.

Avandia was linked to a higher risk of heart attack by a study published by the Cleveland Clinic in May. That study, an analysis of 42 different clinical trials, showed that patients taking Avandia had a 43-percent higher risk of having a heart attack. Following that publication, both the Food & Drug Administration (FDA) and Glaxo where criticized for not taking the heart attack risk more seriously. Testimony at a congressional hearing in June revealed that the company and the FDA had known about the heart attack risk as far back as September 2005. That congressional investigation also uncovered allegations that in 2005, an unnamed FDA scientist who had advocated for a strong black box warning on Avandia about its risk for congestive heart failure had been removed from an Avandia safety review.

On Monday, a Senate Finance Committee report alleged that Glaxo tried to silence Dr. John Buse, a diabetes expert and professor of medicine at the University of North Carolina in Chapel Hill. In 1999, Dr. Buse began expressing concerns about the cardiovascular risks of Avandia. Earlier this summer, the Senate committee heard testimony from Dr. Buse, who said he felt pressured by the drug’s maker, SmithKlineBeecham (now part of GlaxoSmithKline) to sign a clarifying statement drafted by the company that downplayed his concerns. During his testimony, Dr. Buse described name-calling and what he said was the veiled threat of a lawsuit by a high-ranking drug company executive after he had criticized Avandia at a medical meeting. Dr. Buse also testified that Glaxo complained about him to his supervisors at the University of North Carolina. This week’s Senate committee report implicated Glaxo Chief Executive Jean-Pierre Garnier and former research chief Dr. Tachi Yamada in the intimidation campaign against Dr. Buse.

Now, Senators Max Baucus (D-Mont.) and Charles Grassley (R-Iowa) want to speak with Dr. Yamada, who left Glaxo recently to join the Bill and Melinda Gates Foundation. In a letter to Dr. Yamada dated November 16, the Senators requested a meeting with him because of the “significant role” Yamada allegedly played in Glaxo’s campaign against Dr. Buse.

Earlier this week a Glaxo spokesperson told the Wall Street Journal that the company was only trying to correct “inaccuracies” when it contacted Dr. Buse. "People at the time were very passionate about this new medicine and could perhaps have handled the interactions with Dr. Buse better,” the Glaxo spokesperson said. “We did apologize to Dr. Buse for the tone of some of the conversations.”

A representative for Dr. Yamada told Reuters news agency that he would be willing to meet with congressional staff.

GlaxoSmithKline Tried to Intimidate, Silence Avandia Critic Report Says

Mon, 19 Nov 2007 00:00:00 -0800

GlaxoSmithKline, the maker of Avandia, made a concerted effort to intimidate a prominent physician into keeping quiet about some of the controversial diabetes drug’s safety issues, a congressional investigation has found.   The shocking allegations against Glaxo only serve to underscore questionable practices many drug companies use to monitor and influence respected doctors whose opinions can affect sales of medications.

Avandia’s cardiovascular problems have been the subject of concern since May, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. Over the summer, GlaxoSmithKline, the maker of Avandia and the Food & Drug Administration (FDA) came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. Testimony at a congressional hearing in June revealed that the company and the FDA had known about the heart attack risk as far back as September 2005. That congressional investigation also uncovered allegations that in 2005, an unnamed FDA scientist who had advocated for a strong black box warning on Avandia about its risk for congestive heart failure had been removed from an Avandia safety review.

Now, a new Senate Finance Committee report has alleged that Glaxo tried to silence Dr. John Buse, a diabetes expert and professor of medicine at the University of North Carolina in Chapel Hill. In 1999, Dr. Buse began expressing concerns about the cardiovascular risks of Avandia.   Earlier this summer, the Senate committee heard testimony from Dr. Buse, who said he felt pressured by the drug’s maker, SmithKlineBeecham (now part of GlaxoSmithKline) to sign a clarifying statement drafted by the company that downplayed his concerns. During his testimony, Dr. Buse described name-calling and what he said was the veiled threat of a lawsuit by a high-ranking drug company executive after he had criticized Avandia at a medical meeting. Dr. Buse also testified that Glaxo complained about him to his supervisors at the University of North Carolina.

Now, the Senate Committee has implicated two high-ranking Glaxo executives in the intimidation campaign against Dr. Buse. The report alleges that Glaxo Chief Executive Jean-Pierre Garnier and former research chief Tachi Yamada were involved in the intimidation.   Dr. Buse had also named Yamada in testimony to the Senate committee.

For its part, Glaxo told the Wall Street Journal that it denies trying to stifle Dr. Buse. A spokesperson told the newspaper that it disputes the committee's conclusions.   However, the spokesperson conceded that Glaxo had tried to correct Dr. Buse's "inaccuracies" "People at the time were very passionate about this new medicine and could perhaps have handled the interactions with Dr. Buse better," the Glaxo spokesperson said. "We did apologize to Dr. Buse for the tone of some of the conversations.”

Avandia Controversy Won't Go Away with New Heart Attack Black Box Warning

Thu, 15 Nov 2007 00:00:00 -0800

Avandia is getting yet another break from the Food & Drug Administration (FDA). While the FDA did announce the addition of a long-awaited black box warning for Avandia’s increased risk of heart attacks, it is not the strongly worded warning that many patient advocates had call for. But that should surprise no one, as it simply repeats the FDA’s past pattern of turning a blind eye to Avandia safety problems.

Avandia’s heart attack link has been a subject of concern since May, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. Over the summer, GlaxoSmithKline, the maker of Avandia, and the FDA came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. Testimony at a congressional hearing in June revealed that the company and the FDA had known about the heart attack risk as far back as September 2005. That congressional investigation also uncovered allegations that in 2005, an FDA scientist who had advocated for a strong black box warning on Avandia about its risk for congestive heart failure had been removed from an Avandia safety review.

Now comes this weakly worded heart attack warning. While the new black box mentions the Cleveland Clinic heart attack study, it also says that the Avandia – heart attack link is “inconclusive”. In comparison, Canada’s regulatory agency issued a much stronger Avandia warning last week. Under the direction of Health Canada, Glaxo sent a letter to Canadian health professionals informing them that Avandia can no longer be prescribed as monotherapy for type 2 diabetes, except when metformin use is contraindicated or not tolerated. Health Canada has also withdrawn its approval for Avandia to be used in combination with a sulfonylurea, except when metformin is contraindicated or not tolerated. Finally, the letter said that treatment with Avandia is now is now contraindicated in patients with any stage of heart failure.

While many Avandia critics in the US were hoping for the FDA to take action similar to that of Health Canada, the new wording of the black box warning is not suprising. Last month, Glaxo confirmed that it was “negotiating” with the FDA over the wording for a black box warning for heart attack risk, so obviously the company had a lot to say about the warning’s make-up. And just one day before the Avandia black box warning was announced, Glaxo’s CEO told Reuters news agency that he thought Avandia sales would rebound as long as the black box warning wasn’t too strong.

In announcing the new black box warning, the FDA did say that it was requiring Glaxo to perform more clinical trials on Avandia’s heart attack risks. But once again, Glaxo will be paying for and supervising those Avandia trials, so there’s no telling how thorough they’ll be. Obviously, the new black box heart attack warning will not mean the end of the Avandia controversy.

Avandia Black Box Heart Attack Warning Finally Approved

Wed, 14 Nov 2007 00:00:00 -0800

Avandia will finally bear a new black box warning about heart attack risks associated with the controversial diabetes drug, the Food & Drug Administration (FDA) announced today. The black box warning had been sought by patient advocates ever since Avandia was linked to an increased risk of heart attacks earlier this year. The FDA aid that Avandia’s maker, GlaxoSmithKline, had also agreed to conduct a large scale clinical trial of heart attack risks associated with Avandia.

The FDA has been considering an additional heart attack black box warning for Avandia since July, after an advisory panel recommended the new cautions. That same panel had voted to allow Avandia to remain on the market, even though it agreed that there was evidence that the diabetes drug did in fact increase heart attack risk. Avandia’s heart attack link has been a subject of concern since May, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. On August 14, the FDA had upgraded the Avandia label to include a warning about congestive heart failure.

According to the FDA press release announcing the Avandia heart attack black box warning, the new caution would include the following statement: “A meta-analysis of 42 clinical studies (mean duration 6 months; 14,237 total patients), most of which compared Avandia to placebo, showed Avandia to be associated with an increased risk of myocardial ischemic events such as angina or myocardial infarction. Three other studies (mean duration 41 months; 14,067 patients), comparing Avandia to some other approved oral antidiabetic agents or placebo, have not confirmed or excluded this risk. In their entirety, the available data on the risk of myocardial ischemia are inconclusive.” The FDA also said that Glaxo was working on new medical guide for Avandia patients.

Avandia was Glaxo’s number two selling drug prior to the May heart attack revelations. Since the Cleveland Clinic study was published, sales have dropped 48 percent. Some large insurers, including the Department of Veterans Affairs, have dropped Avandia from their prescription drug formularies. Over the summer, Glaxo and the FDA came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. Testimony at a congressional hearing in June revealed that the company and the FDA had known about the heart attack risk as far back as September 2005. That congressional investigation also uncovered allegations that in 2005, an FDA scientist who had advocated for a strong black box warning on Avandia about its risk for congestive heart failure had been removed from an Avandia safety review.

Avandia Heart Attack Warning from FDA Imminent, As Glaxo CEO Says Avandia Sales Could Rebound

Tue, 13 Nov 2007 00:00:00 -0800

Avandia could soon bear a long-awaited black box warning about its potential to cause heart attacks, as media outlets are reporting that a Food & Drug Administration (FDA) decision on the warning’s wording could be handed down in days. If true, the new black box warning would be announced just after the CEO of GlaxoSmithKline boasted that Avandia sales could rebound depending on the wording of the heart attack warning.

Avandia already bears a black box warning – the FDA’s strictest caution – regarding its relationship to congestive heart failure. The FDA has been considering an additional heart attack black box warning for Avandia since July, after an advisory panel recommended the new cautions. That same panel had voted to allow Avandia to remain on the market, even though it agreed that there was evidence that the diabetes drug did in fact increase heart attack risk. Avandia’s heart attack link has been a subject of concern since May, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. Since then, sales of the drug – once a best seller for Glaxo – have fallen by more than 48 percent following the revelations.

But Glaxo CEO Jean-Pierre Garnier told Reuters that the new Avandia black box heart attack warning was not necessarily bad news for the drug or the company. In fact, Garnier said that he expected Avandia sales to rebound, depending on the black box’s wording. "It's not the black box that matters or the lack of black box, that's not important to me; it's -- what is it saying?" Garnier told the Reuters Health Summit in New York.

Last month, Glaxo confirmed that it was “negotiating” with the FDA over the wording for a black box warning for heart attack risk. Given the FDA’s prior conduct in relation to Avandia’s safety issues, Garnier’s words will likely not comfort many patient safety advocates. Over the summer, Glaxo and the FDA came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. Testimony at a congressional hearing in June revealed that the company and the FDA had known about the heart attack risk as far back as September 2005. That congressional investigation also uncovered allegations that in 2005, an FDA scientist who had advocated for a strong black box warning on Avandia about its risk for congestive heart failure had been removed from an Avandia safety review. Given that track record, it is possible to read quite a bit into Garnier’s optimism over Avandia sales.

Exactly what Garnier’s statements indicated could become apparent in the next few days. Dr. Janet Woodcock, the FDA's deputy commissioner for operations, confirmed to Reuters that the agency’s internal Drug Safety Oversight Board had delivered a recommendation to her office but declined to reveal its contents. According to Woodcock, an announcement regarding the new Avandia black box warning could come any day.

Avandia Faces Tough New Restrictions in Canada Due to Heart Attack Risk

Wed, 07 Nov 2007 00:00:00 -0800

Avandia has been hit with new restrictions by Canadian regulatory authorities following reports that the controversial diabetes drug puts patients at a higher risk for heart attacks and other cardiac problems. The new Canadian Avandia restrictions will no doubt further weaken sales of the medication, which had already fallen 60% since questions about the drug’s safety were first raised.

The new Avandia restrictions were requested by Health Canada, the agency which regulates drugs in that country. Health Canada said that its request was prompted by reports of adverse events linked to Avandia, as well as published studies that indicated it put users at an increased risk for heart problems. Those studies included one published in May by the Cleveland Clinic that showed that patients taking Avandia had a 43-percent higher risk of having a heart attack.

GlaxoSmithKline, the manufacturer of Avandia, sent a letter to Canadian health professionals informing them that Avandia can no longer be prescribed as monotherapy for type 2 diabetes, except when metformin use is contraindicated or not tolerated. Health Canada has also withdrawn its approval for Avandia to be used in combination with a sulfonylurea, except when metformin is contraindicated or not tolerated. Finally, the letter said that treatment with Avandia is now is now contraindicated in patients with any stage of heart failure.

Health Canada is only the latest regulatory agency to restrict Avandia usage. Last month, the United States Department of Veterans Affairs (VA) announced that it was dropping Avandia from its prescription drug formulary. In a statement announcing the move, the VA said that it had conducted its own review and concluded that, for some patients, Avandia did not afford the same margin of safety as other diabetes medications. The VA said that it would still make Avandia available for patients who were currently taking it and wanted to continue. However, the VA urged doctors to discuss Avandia’s safety issues with these patients. But the decision means that patients not currently prescribed Avandia will not be able to get it through the VA in the future. Prior to its announcement, the VA accounted for about 8% of Avandia’s sales in the United States.

In July, the Food & Drug Administration (FDA) convened a panel to discuss the issues surrounding Avandia’s heart attack risk. The panel voted 20-3 that the drug did in fact raise the chance of heart attacks, yet the panel still voted 22-1 to allow it to remain on the market. The advisory panel did recommend that stronger heart attack warnings be added to the Avandia label, and the FDA is currently working with GlaxoSmithKline to develop a black box warning for Avandia regarding heart attack risks.

Avandia Vote at FDA Kept Secret, Leads to Questions From US Senator

Tue, 30 Oct 2007 00:00:00 -0700

Avandia may have been the subject of a secret vote by a Food & Drug Administration (FDA) panel in which it apparently decided by a one-vote margin to keep the controversial drug on the market. Now, a member of the US Senate wants to know if the report of the 8-7 vote by the FDA’s Drug Safety Oversight Board is accurate, and if so, why the agency has yet to make this vote public.

Avandia has been under intense scrutiny since May when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. During a congressional hearing earlier this summer, the drug’s maker, GlaxoSmithKline, and the FDA have came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. Testimony at that hearing revealed that the company and the FDA had known about the heart attack risk as far back as September 2005. In July, the FDA convened a panel to discuss the issues surrounding Avandia’s heart attack risk. The panel voted 20-3 that the drug did in fact raise the chance of heart attacks, yet the panel still voted 22-1 to allow it to remain on the market.

Now, the FDA’s conduct in relation to Avandia is being called into question by Senator Charles Grassley, the leading Republican on the Senate Finance Committee. According to Senator Grassley’s office, the committee recently learned that the Drug Safety Oversight Board had voted 8-7 on October 2 to keep Avandia on the market. While the board’s meetings are not open to the public, details of these meetings are published on the FDA website. So far, this has not been done.

Now Senator Grassley wants information on that meeting and vote, and he said in a statement that the FDA’s failure to inform the public of the close Avandia vote presents “new rounds of questions about the way the FDA monitors and assesses drug risks and decides whether to let the public know about emerging risks.” So far, the FDA has not responded to the Senator’s concerns.

GlaxoSmithKline, which continues to insist that Avandia is safe, is currently negotiating with the FDA to include a new black box warning about the drug’s heart attack risks on its labels. It is not known when that new warning will finally appear on Avandia.

Avandia Black Box Warning on Heart Attack Risk Could Soon Be a Reality

Wed, 24 Oct 2007 00:00:00 -0700

An Avandia black box warning about its potential to cause heart attacks could soon appear on the drug’s label if officials at the Food & Drug Administration (FDA) have their way. The FDA is said to be pushing hard for the black box warning, the FDA’s strictest, to be including on Avandia’s label regarding the heart attack risks associated with the controversial diabetes drug. Avandia already carries a warning about heart failure risks, but a new black box heart attack warning would be far more serious.

Avandia has been a subject of debate since May 21, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. Since the Cleveland Clinic study was published, a great deal of controversy has swirled around Avandia. In June, Congress held hearings to discuss Avandia and the FDA’s handling of its safety issues. At those hearings, it was revealed that GaxoSmithKline, Avandia’s manufacturer, had informed the FDA of a study it had conducted that produced similar results. However, both the agency and the manufacturer felt that more investigation was needed before conclusions could be made about Avandia’s possible safety issues. Since those revelations were made public, the FDA has been under a great deal of pressure to take action on Avandia.

In July, the FDA convened a panel to discuss the issues surrounding Avandia’s heart attack risk. The panel voted 20-3 that the drug did in fact raise the chance of heart attacks, yet the panel still voted 22-1 to allow it to remain on the market. They recommended that Avandia be given a warning label about the cardiac problems.

If labeling changes are adopted, the new Avandia black box warning would focus on the drug’s risk of ischemic heart problems, or events in which blood is unable to reach the heart. The FDA’s own analysis of various Avandia studies had found that the drug carries a 38% higher risk of causing such problems. For its part, GlaxoSmithKline continues to insist that Avandia poses no more risk than other diabetes drugs, and that other studies have shown it to be safe.

The addition of a black box warning on Avandia could be a further drag on sales of the drug, which have dropped more than 60% since the release of the Cleveland Clinic study. Just last week, the Department of Veterans Affairs (VA) announced that it was removing Avandia from its prescription drug formulary. The VA said that it would still make Avandia available for patients who were taking it now and wanted to continue. But the decision means that patients not currently prescribed Avandia will not be able to get it through the VA in the future. Right now, the VA accounts for about 8% of Avandia sales.

GlaxoSmithKline has acknowledged that it is working with the FDA to formulate a new warning label for Avandia. The FDA will make the new Avandia black box warning public once it is finalized.

Avandia Removed from Veteran Affairs Drug Formulary

Thu, 18 Oct 2007 00:00:00 -0700

Avandia will no longer be a drug of choice for The Department of Veterans Affairs (VA). The decision to remove rosiglitazone, known by the brand name Avandia, from the VA drug formulary comes after months of debate over the diabetes medication’s safety.   The VA’s decision is a blow to GlaxoSmithKline, the maker of the drug, because the department makes up about 8% of Avandia’s sales.

In a statement announcing the move, the VA said yesterday that “The Department of Veterans Affairs conducted its own review and has concluded that, for some patients, rosiglitazone may not afford the same margin of safety as alternative drug therapies.” The VA said that it would still make Avandia available for patients who were taking it now and wanted to continue. However, the VA has urged doctors to discuss Avandia’s safety issues with these patients.   But the decision means that patients not currently prescribed Avandia will not be able to get it through the VA in the future.

The decision by the VA is not a good one for GlaxoSmithKline, which has already seen sales of Avandia drop by 60% since concerns over its safety were first raised. While removing the drug from the VA formulary will have an impact on Avandia sales, the effect could be far worse if many VA patients currently taking Avandia decide to switch to something else.   Between September 2006 and August 2007, the VA had issued more than 160,000 Avandia prescriptions.

Avandia has been a subject of debate since May 21, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. Following the publication of that study, it was revealed that in 2005, GlaxoSmithKline, Avandia’s manufacturer, had informed the FDA of a study it had conducted that produced similar results. However, both the agency and the manufacturer felt that more investigation was needed before conclusions could be made about Avandia’s possible safety issues. As a result, the cardiac problems were not made public until the Cleveland Clinic published its analysis in May.

In July, the FDA convened a panel to discuss the issues surrounding Avandia’s heart attack risk. The panel voted 20-3 that the drug did in fact raise the chance of heart attacks, yet the panel still voted 22-1 to allow it to remain on the market. As a result of that meeting, new warnings were added to Avandia’s label. The advisory panel recommendations are not binding, and the FDA could still take more drastic action.   The FDA safety review is ongoing, and there are many at the agency pushing to have Avandia removed from the market.

Avandia Study Says Drug Increases Chance of Heart Failure

Fri, 28 Sep 2007 00:00:00 -0700

Yet another study has found that Avandia and Actos, popular diabetes drugs, raise a patient’s risk for heart failure. These new findings are just the latest to cast doubts on the safety of these medications, which have been under scrutiny for some time.

Actos and Avandia are drugs known as thiazolidinediones, or TZDs and are used to lower blood sugar.   These drugs have been under scrutiny since May when a study of 42 clinical trials conducted by the Cleveland Clinic showed that patients taking Avandia had a 43% higher risk of having a heart attack, and a 64% higher chance of sudden cardiac death. The Cleveland Clinic study also found that Avandia nearly doubled the risk for heart failure. That study caused the Food & Drug Administration (FDA) to convene a hearing of an advisory panel to discuss Avandia’s heart attack risks. While the panel agreed that patients using Avandia do face a greater risk of heart attack, and the diabetes drug should bear the strictest FDA warnings, it stopped short of recommending that Avandia be pulled from the market entirely. Both Actos and Avandia already carry warnings that they may cause or worsen congestive heart failure, a condition in which the heart does not pump blood efficiently.

Published in the Lancet, the latest study was conducted by researchers at the Lahey Medical Center in Massachusetts. Like most other research into these drugs, it was a meta-analysis, meaning that it pooled data from many different clinical trials. This particular study took data from seven trials where more than 20,000 patients with type 2 diabetes or pre diabetes were given Actos or Avandia.   The overall risk of heart failure in all patients was around 72% percent higher than it is the general population.   Patients with a history of heart disease and heart failure had he highest risk of developing heart failure when using Actos or Avandia. However the Lahey study did not find an increased risk of cardiac death in patients using these drugs, something that other research has pointed to.

The authors of the Lahey study claim that the data they examined was more robust than those the Cleveland Clinic analyzed.   The researchers had a panel of experts determine if any heart attacks had occurred in the clinical trials they analyzed.   Also, the seven clinical trials used in the Lahey study had all been previously published.

While the Lahey researchers found that Actos and Avandia both were effective in controlling blood sugar, an accompanying editorial in the Lancet criticized researchers for using reduced blood sugar levels as evidence of a drug’s success.   Rather, it said they should focus more on patient outcomes such as quality of life and survival. The editorial recommends that drug companies conduct further clinical trials of their medications after they are on the market. “Regulatory agencies must hold manufacturers’ feet to the fire to ensure that these are performed,” it says. “Unless limitations on the understanding, analysis, and communication of drug safety issues are addressed, the TZDs will simply become the latest in a series of preventable drug disasters.

Avandia Safety Questioned By More Studies

Wed, 12 Sep 2007 00:00:00 -0700

Avandia has come under fire again, after two more studies raised additional concerns over the safety of the diabetes medication. The new research could add to pressure on the Food & Drug Administration (FDA) to further regulate the controversial drug, and will undoubtedly cause many more doctors to cease prescribing Avandia.   Sales of Avandia had already plunged over the summer after an earlier study indicated the drug could increase a patient’s risk of suffering a heart attack.

Both studies were published in the Journal of the American Medical Association. The first found that Avandia doubled the risk of a patient developing heart failure, and increased the chance of heart attack by 42 percent. The second study found that another diabetes drug, Actos, actually provided patients some protection from heart attacks, strokes and death, although it also increased the risk of heart failure. An accompanying editorial only added fuel to the controversy by claiming that had Avandia’s heart attack risk been known in 1999, it would have never been granted FDA approval.

Avandia has been a subject of debate since May 21, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. Following the publication of that study, it was revealed that in 2005, GlaxoSmithKline, Avandia’s manufacturer, had informed the FDA of a study it had conducted that produced similar results. However, both the agency and the manufacturer felt that more investigation was needed before conclusions could be made about Avandia’s possible safety issues. As a result, the cardiac problems were not made public until the Cleveland Clinic published its analysis in May.

The first of the two studies published in the Journal was conducted by researchers from Wake Forest University.   It was similar to the analysis published by the Cleveland Clinic in May, but was limited to four long-term clinical trials. The results of the Wake Forest analysis were strikingly similar to the Cleveland Clinic’s earlier findings.

The second was conducted by the Cleveland Clinic, and analyzed data from 19 clinical trails on Actos.   The study found that Actos actually lowered the risk of heart attacks, stroke and death by 20-percent. Although Actos also increased a patient’s risk of heart failure, those problems are reversible.

Dr. Sonal Singh, a co-author of the Wake Forest Study, told the New York Times that doctors should reconsider prescribing Avandia. “There are older and cheaper drugs that are far better to treat diabetes.” He also said that in addition to the risks of heart failure and heart attacks, Avandia also can lead to blindness, and can cause bone fractures in women

In July, the FDA convened a panel to discuss the issues surrounding Avandia’s heart attack risk. The panel voted 20-3 that the drug did in fact raise the chance of heart attacks, yet the panel still voted 22-1 to allow it to remain on the market. As a result of that meeting, new warnings were added to Avandia’s label. But in an editorial published along with the new studies, two doctors from Boston’s Brigham and Woman’s Hospital wrote that had such a lopsided vote on Avandia’s heart risks taken place prior to its approval, the drug would never have gotten on to the market. And Dr. Steven Nissan, an author on both Cleveland Clinic studies, told USA Today that the new research should put more pressure on the FDA to reconsider Avandia.

Clues to Avandia Heart Failure Risk Uncovered

Fri, 07 Sep 2007 00:00:00 -0700

Avandia and other drugs in its class that are used to treat Type II diabetes have been linked to increased risk of heart failure, but the reasons behind this deadly side effect were poorly understood. Now, an experiment involving mice has given researchers clues to the reasons behind this heart failure connection. The study, conducted by researchers at the Columbia College of Physicians and Surgeons, found that PPARg agonists like Avandia can increase the uptake of both glucose and triglycerides in cardiac tissue. Such an occurrence can lead to or exacerbate heart failure, and the mice in the study developed cardiomyopathy.

To evaluate the effects of Avandia on the heart, the researchers used two types of mice. The mice were bred to over-express PPARg, the nuclear receptor that is targeted by drugs like Avandia. Some mice were bred to over-express PPARg at high-levels, while the other group over-expressed it at lower levels. The mice were also bred to have dilated left ventricles, impaired systolic function and increased heart-to-body ratios and other signs associated with heart failure. When the mice were exposed to Avandia, the treatment caused further deterioration of heart function including lipid accumulation and larger hearts.

When the researchers compared PPARg expression levels in the hearts of the mice and human hearts, they found that the expression in human hearts was greater. This would suggest that PPARg has a bigger impact on human hearts. The researchers wrote that “While PPARg antagonists appear to have multiple beneficial affects, their direct actions on the myocardium have the potential to lead to deterioration in heart function.”

Avandia carries a black box warning about its potential to cause or exacerbate heart failure, and it is not recommended for patients with heart failure. The drug became a subject of controversy in May when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. Earlier this summer, the Food & Drug Administration (FDA) convened an advisory panel to look into safety issues surrounding Avandia. The panel found that patients using the drug did face a greater risk of heart attack, and recommended that its label include the strongest FDA warning possible regarding this risk. However, the panel stopped short of recommending that Avandia be pulled from the market. The panel also said that there was a need for more studies on the safety issues surrounding Avandia.

FDA Approving Fewer New Drugs in Wake of Vioxx, Avandia, Other Scandals

Thu, 23 Aug 2007 00:00:00 -0700

The Food & Drug Administration (FDA) is still struggling to regain credibility after its approval process came under fire as a result of scandals surrounding drugs like Vioxx, Avandia and Ketek. That could be one reason why the FDA is approving new medications at a much slower rate than in the past. Since January, the FDA has approved only 38 new drugs. During the same period in 2006, the FDA had already approved 55 new medications.

In the past several years, the FDA’s drug approval process has been criticized for allowing defective drugs to go on the market even when serious questions were raised about their safety. Ketek is a prime example of the FDA’s lax approval process. Ketek, an antibiotic used to treat sinus infections, was granted FDA approval in 2004, even though the FDA had found serious irregularities in clinical trials conducted by its manufacturer, Sanofi-Aventis. At least one doctor involved in the trial falsified data and was sent to prison for fraud. Still, Ketek was approved by the FDA in 2004. Shortly after it approved Ketek, the FDA began receiving reports that linked it to liver problems. The FDA eventually confirmed 53 cases of liver failure in patients using the antibiotic, including five deaths. This past February, the FDA finally added black box warnings to the Ketek label and severely restricted its use.

Vioxx, another FDA approved drug, has been linked to severe heart problems. In 2004, an FDA study estimated that this defective drug could have contributed to 27,785 heart attacks and sudden cardiac deaths between 1999 and 2003. After Vioxx was pulled from the market in 2004, it was revealed that the FDA had tried to silence the drug expert who headed that study. Dr. David Graham, associate director for science in the FDA Drug Center's Office of Drug Safety, told Senate investigators that he had been subjected to veiled threats and intimidation when he informed the FDA of his findings.

Avandia is another drug that has caused the FDA a great deal of embarrassment. In May, a study by the Cleveland Clinic found that the diabetes drug increased a patient’s risk of heart attack by 43-percent. In June, a congressional committee convened hearings to investigate problems with the drug. The committee heard testimony from Dr. John Buse, a diabetes expert who raised questions about Avandia’s cardiac risks in 1999. Dr. Buse told the committee that he felt pressured by the drug’s maker, SmithKlineBeecham (now part of GlaxoSmithKline) to sign a clarifying statement drafted by the company that downplayed his concerns. Testimony at that hearing also revealed that the manufacturer and the FDA had known about Avandia’s heart attack risk as far back as September 2005. However, the agency felt that more investigation was needed before conclusions could be made about Avandia’s possible safety issues.

All of these scandals have damaged the public’s confidence in the FDA’s ability to insure drug safety. The fact that the FDA has approved fewer new medications this year could be a sign that the agency is finally starting to take that seriously.

Avandia, Other Diabetes Drugs to Carry Stronger Heart Failure Warnings

Wed, 15 Aug 2007 00:00:00 -0700

The diabetes drug Avandia will now carry stronger warnings about heart failure risks, the Food & Drug Administration (FDA) said yesterday.   Avandia, marketed by GlaxoSmithKline, is one of a class of diabetes drugs called thiazolidinediones that will carry the black box warning.

This class of drugs already had heart failure warnings on its labels, but they were buried deep within the label information.   The FDA had asked all the manufacturers of thiazolidinediones to add the more prominent black box warnings in June, after the agency received reports that patients with heart failure had still taken the drugs and had died.   In addition to Avandia, Glaxo manufactures two other thiazoldinediones, Avandaryl and Avandamet.   Another company, Takeda, markets two thiazoldinediones under the names Actos and Duetact.

The new warnings will say that patients with the most severe forms of heart failure should not take the drugs, and that thiazoldinediones are not recommended for patients with heart failure that causes symptoms. The warnings also advise that doctors should reconsider the use of the drugs if a patient develops heart failure while taking thiazoldinediones.

The new warnings do not address a higher risk of heart attack that could be a side effect of thiazoldinediones.   In May, the Cleveland Clinic had published a study showing that patients taking Avandia had a 43-percent higher risk of having a heart attack. After that study was published, Avandia became the subject of much controversy. In July, an FDA advisory panel voted to keep Avandia on the market despite the heart attack risk, but the panel also recommended that the drug bear the strongest possible FDA warnings about heart attacks. The FDA said that it is continuing to evaluate Avandia’s heart attack risks and the need for such a warning.

Over the summer both Glaxo and the FDA came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. Testimony at a congressional hearing in June revealed that the company and the FDA had known about a possible heart attack risk as far back as September 2005. However, both the agency and the manufacturer felt that more investigation was needed before conclusions could be made about Avandia’s possible safety issues. As a result, the cardiac problems were not made public until the Cleveland Clinic published its analysis in May.

That same congressional hearing also shed light on disturbing facts surrounding the FDA’s approval review of Avandia. At least one doctor testified that in 1999, he was pressured into downplaying his concerns with the medication’s cardiac side effects after Glaxo threatened him with legal action. It was also revealed that following its approval of the drug, the FDA had never required the manufacturer to conduct a post-market study of Avandia’s possible heart risks, even though an FDA reviewer had suggested such a study be done.

Avandia the Defective Drug and its Maker GlaxoSmithKline Under Heat Lamp

Tue, 31 Jul 2007 00:00:00 -0700

Patients using Avandia do face a greater risk of heart attack, and the diabetes drug should bear the strictest Food & Drug Administration (FDA) warning possible, said an FDA Advisory Panel investigating the medication’s safety. But the panel stopped short of recommending that Avandia be pulled from the market, even as one of its own members urged it to do so.

That member, FDA Safety Reviewer Dr. David Graham, contended that any increased cardiac risk was unacceptable. In the past, Dr. Graham has blasted Avandia safety trails conducted by GlaxoSmithKline as being “useless”. In his testimony, Dr. Graham argued that because most diabetes patients will eventually die from heart problems, any drug that raises heart attack risk is too dangerous.

Avandia has been under scrutiny since May 21, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. During yesterday’s hearing, GlaxoSmithKline defended Avandia, saying that its own clinical trails showed that the drug posed no more risk of heart attack than other drugs.

In the past, Dr. Graham has attacked those studies, which were funded by GalxoSmithKline. In documents he posted on the FDA website on June 26, Dr. Graham argued that GlaxoSmithKline's studies “suffer from a profound lack of statistical power” because one did not include a placebo group, and because doctors knew what drug their patients were taking. Dr. Graham wrote that the design of the trials rendered them “useless”.

The advisory panel voted 22-1 to recommend that Avandia remain on the market. In doing so, they asserted that the findings of the Cleveland Clinic study were not conclusive enough, especially since other trails – notably GlaxoSmithKline’s – came to different conclusions. “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 and the panel's patient representative.

Still, the panel voted 20-3 that Avandia did carry a risk of heart attack. They recommended that the drug be given a warning label about the cardiac problems. The panel also said that there was a need for more studies on the issue. The FDA is not bound by any of the panel’s recommendations.

Dr. Graham, who has been outspoken in the past on safety issues surrounding other drugs like Vioxx, asserted that the panel’s decision made no sense, saying that it “violates the principle taught us all in medical school ... 'First, do no harm.'

Avandia Lawyer Liver Failure Attorney Side Effects

Tue, 31 Jul 2007 00:00:00 -0700

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Avandia Liver Failure Injury Lawyers

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The lawyers and attorneys at our firm are offering free case evaluations to victims of Avandia side effects. Since being introduced in 1999, Avandia has been linked to a variety of serious side effects, including fatal liver failure, cardiovascular problems, edema and bone fractures. If you or someone you love suffered from one of these problems while taking Avandia, you may be entitled to compensation. Please contact one of our Avandia injury lawyers as soon as possible to protect your legal rights.

At its peak in 2006, 13.2 million people had taken Avandia. But by 2008, concerns over side effects had caused that number to fall to 4.6 million. In October 2008, safety worries prompted the American Diabetes Association (ADA) and the European Association for the Study of Diabetes to unanimously advise against using Avandia. Still, an estimated 10,000 prescriptions are written for Avandia in the U.S. every day. Our Avandia injury lawyers believe this drug has the potential to injure, and even kill, thousands of people.

Avandia and Liver Failure

The Avandia injury lawyers at our firm are currently investigating potential lawsuits against GlaxoSmithKline on behalf of victims of Avandia-induced liver failure. In October 2008, the consumer advocacy group Public Citizen petitioned the Food & Drug Administration (FDA) to remove Avandia from the U.S. market because of its association with liver failure.

Public Citizen petitioned the FDA after the group identified 14 cases of Avandia-induced liver failure, including 12 deaths. These cases were derived from the FDA Adverse Event Reporting System after Public Citizen reviewed the agency’s MedWatch forms, which are submitted to the agency when adverse drug reactions are suspected.

Public Citizen's petition pointed out that potentially fatal liver failure was just one of many problems associated with Avandia. The group said in a press release that the drug increases the risk of heart attack approximately 40 percent, doubles the risk of heart failure and bone fractures, and increases the risk of anemia and vision loss from macular edema, a swelling of the retina caused by fluids accumulating in the eye.

“The scientific consensus against Avandia is overwhelming,” Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group, said in the press release. “The timing of these findings should give the FDA the momentum it needs to act swiftly to prevent further needless deaths and health damage by banning this drug.”

Avandia and Heart Problems

The Avandia injury lawyers at our firm are also offering case evaluations to victims of Avandia-induced heart failure and heart attacks. In May 2007, a Cleveland Clinic study published in the New England Journal of Medicine found that patients taking Avandia had a 43-percent higher risk of having a heart attack. The study created a firestorm, and many called for Avandia to be recalled at that time.

That summer, Glaxo and the FDA came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. Testimony at a congressional hearing in June 2007 revealed that the company and the FDA had known about the heart attack risk as far back as September 2005. That congressional investigation also uncovered allegations that in 2005, an FDA scientist who had advocated for a strong black box warning on Avandia about its risk for congestive heart failure had been removed from an Avandia safety review.

In August 2007, the FDA finally approved a black box warning - the agency's strictest safety notice - for Avandia about its link to heart attacks. The Avandia black box warning included the following statement: “A meta-analysis of 42 clinical studies (mean duration 6 months; 14,237 total patients), most of which compared Avandia to placebo, showed Avandia to be associated with an increased risk of myocardial ischemic events such as angina or myocardial infarction.”

In August 2007, the FDA also approved a black box warning for Avandia about its association with congestive heart failure. The new warning said that patients with the most severe forms of heart failure should not take the drug, and that thiazolidinediones are not recommended for patients with heart failure that causes symptoms. The warnings also advise that doctors should reconsider the use of drugs like Avandia if a patient develops heart failure while taking thiazolidinediones.

Avandia and Vision Problems

The Avandia injury lawyers at our firm are also investigating reports of Avandia-related macular edema. According to Public Citizen's 2008 petition, there were 39 times more reports of macular edema per million prescriptions filled for Avandia than for an older diabetes drug, glipizide.

In January 2006, the FDA and GlaxoSmithKline said that patients who have taken Avandia reported blurry vision and swelling of the feet and legs. GlaxoSmithKline stated it had received some reports of new or worsening diabetic macular edema in diabetic patients who took Avandia. The swelling of the retina can cause blurry or distorted vision. Additionally, most of those patients also reported peripheral edema, or swelling of the legs, ankles and feet. In some situations, stopping treatment or reducing the dose if Avandia eliminated or improved the condition.

Avandia and Bone Problems

The Avandia injury lawyers at our firm are also investigating reports of Avandia-related bone fractures in many patients. According to a Swiss study published in April 2008, the risk of fractures increased among Avandia patients who took the drug for approximately 12 to 18 months. The risk was highest for those with two or more years of therapy. The researchers came to their conclusions by comparing the records of 1,020 diabetic patients with fractures diagnosed by British doctors between 1994 and 2005 against a control group of diabetics who did not have fractures.

In December 2007, researchers doing experiments with mice discovered a possible reason for this Avandia side effect. Avandia appears to throw the body’s system for removing and replacing old bone cells off balance in two important ways. In addition to inhibiting the action of osteoblasts, cells in the body that build bone, researchers also discovered that Avandia stimulates the action of osteoclasts, cells that degrade bone.

The Avandia researchers, whose work was published in the December 2007 issue of Nature Medicine, surmised that the medication’s effect on these cells could account for Avandia’s bone fracture side effects. While there are medications available to counter the Avandia bone fracture risk, the authors of the December 2007 study recommended that all Avandia patients be monitored for bone problems.

Legal Help for Victims of Avandia Injuries

Considering the unacceptably high number of dangerous side effects associated with Avandia, it is clear that this drug was not subject to adequate testing. The Avandia injury lawyers at our firm are committed to making sure that GlaxoSmithKline is held accountable for this negligence.

If you or someone you love suffered from liver failure, heart problems, vision problems or bone fractures as a result of Avandia, you have valuable legal rights. Please fill out our online form or call 1 800 LAW INFO (1-800-529-4636) as soon as possible to discuss your case with one of our Avandia injury lawyers.