Bayer forced to recall Contour TS diabetes strips in seven countries

Bayer AG announced a seven-country recall of Contour TS diabetes test strips due to a manufacturing problem that could lead to blood sugar readings higher than actual levels of glucose. According to a release from the U.S. Food and Drug Administration, glucose test results returned by the recalled strips generally show up five to 17 percent higher than the user’s actual glucose levels.

The recalled Contour TS test strips have lot numbers beginning with WK followed by the characters 7D, 7E, 7F or 7G and then followed by a series of other numbers and letters (for example WK7ED3E52C). The recalled lots have the characters 7D, 7E, 7F, or 7G in the third and fourth position in the sequence.

Consumers may contact Bayer at 1-800-348-8100 to return recalled test strips for a replacement.

Source: U.S. Food and Drug Administration, MedWatch, “Test Strip Recall for CONTOUR TS,” December 21, 2007.

Novartis’ diabetes drug future delayed due to liver-safety problems

Patients could suffer from liver-enzyme elevation

On November 7, 2007, Novartis AG announced that high doses of its diabetes drug, Galvus, could cause liver-safety problems. The announcement has delayed the drug’s path to approval and has raised questions about its future. The company said it would seek a revision to fix the problem before introducing it in Europe.

Patients taking 100 milligram doses of Galvus once-a-day were more prone to have liver-enzyme elevation when compared to patients taking 50 milligrams a day or 50 milligrams twice daily. Recommendations from the company will probably include changing doses to once- or twice-daily 50 milligram doses.

Galvus was approved by the European Union, but the new finding and announcement may delay its debut by several months as the label is finalized. Novartis intends to submit Galvus for approval in the U.S. in 2009, where separate skin toxicity warnings have set back its approval.

The drug is called a DPP-4 inhibitor, which is designed to enhance the body’s ability to lower elevated blood sugar, and may help control Type 2 diabetes. Drug makers also believe they could become blockbuster drugs because they are not associated with weight gain, a major side effect of some established drugs.

Source: “Novartis Diabetes Drug Delayed,” Reuters, November 7, 2007.

FDA associates Byetta with acute pancreatitis after 30 reports of illnesses

Twenty-one diabetes drug patients hospitalized

The United States Food and Drug Administration (FDA) asked Amylin Pharmaceuticals to change its type 2 diabetes drug’s label to include a warning of acute pancreatitis. The recommendation comes after the agency received 30 reports of the illness in patients taking the drug, Byetta.

Twenty-one patients were hospitalized, five of whom developed serious complications of pancreatitis, such as dehydration and renal failure. Pancreatitis symptoms in six patients began or worsened soon after their dose of Byetta was doubled. Details from three patients indicated the symptoms of pancreatitis returned when Byetta was restarted.

In some of these cases, the FDA said, this evidence suggests an association between Byetta and acute pancreatitis. The agency recommended doctors instruct patients who are taking Byetta to seek medical care if they have unexplained persistent abdominal pain, possibly accompanied by vomiting. If doctors suspect a patient is showing symptoms of pancreatitis, they should discontinue the drug.

Source: Peggy Peck, “FDA wants pancreatitis caution added to exenatide (Byetta) label,” MedPage Today, October 16, 2007.

FDA adds black box warning to Avandia, diabetes drugs

Warning says drugs linked to heart failure

On August 14, 2007, the U.S. Food and Drug Administration (FDA) announced it was placing a black box warning on a class of diabetes drugs that includes Avandia. The warning, which is the most serious warning the agency can give, says the drugs are linked to an increase in heart failure.

The drugs receiving the warning are in a class of antidiabetic drugs called thiazolidinedione. The drugs which will receive the black-boxed warning about heart risks include:

Avandia (rosiglitazone) Actos (pioglitazone) Avandaryl (rosiglitazone and glimepiride) Avandamet (rosiglitazone and metformin) Duetact (pioglitazone and glimepride)

The FDA reviewed adverse event reports for the drugs and found cases of significant weight gain and edema (swelling), which are considered warning signs of heart failure. Continuation of these therapies has also been associated with patient deaths.

Heart failure is a condition characterized by the heart’s inability to properly pump blood. It is a condition that develops over time, and differs from a heart attack.

GlaxoSmithKline manufactures Avandia, Actos and Avandaryl. Avandia was the focus of a July 2007 FDA review because of a possible link to heart attacks. The panel agreed to allow the drug to continue to be marketed.

Takeda manufactures Avandamet and Duetact.

Sources: Jennifer Corbett Dooren, “FDA requires Avandia, Actos to have ‘black box’ warning,” Wall Street Journal, August 15, 2007; “Manufacturers of some diabetes drugs to strengthen warning on heart failure risk,” Food and Drug Administration [Press Release]; August 14, 2007; “Information for Healthcare professionals,” Food and Drug Administration [Information Sheet], August 14, 2007; “Information for Healthcare professionals,” Food and Drug Administration Information Sheet, August 14, 2007.

Review finds Januvia, Byetta no better than older drugs, more expensive

Newer diabetes drugs also cause unpleasant side effects

On July 11, 2007, the National Institute of Diabetes and Digestive and Kidney Diseases published a review of 29 studies that found newer diabetes medicines work about the same as older, cheaper drugs.

Merck & Co.’s Januvia, approved in 2006, and Eli Lilly & Company’s Byetta, approved in 2005, were among those studied. The newer drugs are touted as more beneficial because they do not cause low blood sugar and can lead to weight loss.

But the published review found the newer diabetes drugs are no more effective than older medications available for nearly one-third of the cost. The newer drugs also cause new side effects such as nausea, vomiting, and infections.

For a one month’s supply, or 30 pills, of Januvia, consumers pay nearly $5.50 per pill. A one month’s supply of Byetta, given in an injectable cartridge, costs $200. But 60 pills of metformin, a generic drug for type 2 diabetes, costs $33.99, or about $1.76 a pill.

Researchers who found the newer drugs cause headaches, urinary-tract infections, and other side effects are concerned a patient’s immune-system function may be affected. This is significant for diabetes patients because they are more likely to develop a urinary-tract infection and are at an increased risk of complications.

Source: Michelle Fay Cortez, “Merck’s Januvia, Lilly’s Byetta work no better than older drugs,” Bloomberg.com, July 10, 2007.

Avandamet lawsuit filed in eastern Texas

60-year-old Avandamet user died from heart attack

On the same day the New England Journal of Medicine said the popular diabetes drug rosiglitazone, an ingredient in the diabetes drug Avandia, was linked to a greater risk of heart attack, a 60-year-old patient and user of the drug died of a heart attack. Now his wife and son are suing GlaxoSmithKline (GSK), the drug’s maker, saying it contributed to the man’s death.

Larry Alan Stanford had taken Avandamet, a form of Avandia mixed with another diabetes drug, since early 2005. Now GSK is faced with what could be the first of many Avandia lawsuits or Avandamet lawsuits.

“I believe the evidence will show the company knew there were problems with Avandia, but decided to keep on selling it to Larry and others,” personal injury attorney Stephen Drinnon, who represents the Stanford family, said in a release dated June 20, 2007.

The New England Journal of Medicine said Avandia could raise a patient’s risk of heart attack by 40 percent. The drug linking Avandia and Avandamet is rosiglitazone, a drug the lawsuit against GSK says is deadly.

“Glaxo knew or should have known that its rosiglitazone drug greatly increased plaintiffs’ risks of having a heart attack and /or other negative cardiovascular consequences or of causing sudden cardiac death,” the lawsuit says.

Sources: “Avandia maker sued over heart attack,” Associated Press, June 20, 2007; “Glaxo failed to warn of diabetes drug risks: lawsuit,” Reuters, June 20, 2007.

FDA reprimands its own scientist for Avandia warning

Employee and her staff said Avandia was not safe

On June 12, 2007, USA Today reported on a scientist from the U.S. Food and Drug Administration (FDA) who said her directors reprimanded her for recommending that Avandia get a “black box” warning about congestive heart failure.

Rosemary Johann-Liang, the former deputy director of the Division of Drug Risk Evaluation, said she recommended the Avandia warning on the suggestion of her staff. The FDA is investigating the validity of Johann-Liang’s claims.

In the meantime, the Senate Finance Committee is asking the FDA to make sure no scientist is reprimanded for raising safety questions.

“Those FDA employees dedicated to post-marketing surveillance…should be able to express their opinions in writing and independently without fear of retaliation, or reprimand or reprisal,” Sen. Chuck Grassley wrote in a letter dated June 4, 2007.

Johann-Liang said she wanted to be an advocate for drug safety, but oftentimes, her bosses did not want to hear about it.

“A lot of times the agency doesn’t want to hear that there are problems,” she said. “I think, in general, there is a culture of ‘The drug is always innocent.’”

Specifically Johann-Liang is warning people about Avandia, which she feels is a dangerous drug.

“People are continuing to be hurt,” she said. “Congestive heart failure is a very, very clear adverse reaction syndrome with Avandia.”

Source: Rita Rubin, USA Today, “FDA scientist says she was reprimanded for warning.” June 12, 2007.

Patients start to file cases against Avandia

Shareholders lawsuit seeks class-action status

At least two cases have been filed against GlaxoSmithKline PLC (GSK) about the company’s diabetes drug Avandia. The lawsuits allege that GSK caused patients to suffer heart attacks

Shareholders in GSK. also filed a lawsuit, claiming the company misled investors about the safety of the drug. The lawsuit seeks class-action status and alleges the company failed to acknowledge a link between Avandia and higher risk of heart attacks.

On May 29, 2007, Sharon Ann Dabon filed a suit against GSK claiming Avandia caused her to suffer injuries like heart injury and liver failure. Another case, filed June 1, 2007 by Benjamin Sarconi, claims Avandia caused a heart attack and congestive heart failure.

Some attorneys said the personal injury lawyers for those filing Avandia lawsuits may have difficulty proving the drug caused heart problems because diabetes itself increases a person’s risk for heart attacks.

Source: “Jeanne Whalen,” Shareholders sue Glaxo over Avandia disclosure,” Wall Street Journal, June 13, 2007.

Cheatham, MannKind settle lawsuit over new diabetes drug

Whistleblower says former employer withheld information from FDA about Technosphere

While a jury in the Los Angeles County Superior Court deliberated a wrongful termination case on June 5, 2007, Wayman Wendell Cheatham settled with his former employer, MannKind Corp., out of court.

Cheatham alleged that MannKind, the maker of a new diabetes drug, Technosphere, withheld important information from the FDA during the drug’s trials. He did not suggest the drug is dangerous.

Cheatham claimed MannKind hid unexpected lab test results that showed Technosphere, a new inhaled form of insulin, demonstrated potentially more potency than expected. Cheatham said the company did not contact the FDA about the results.

While neither side would release the terms of the settlement, Cheatham’s suit sought $4 million in damages.

Sources: Daniel Yi, , “MannKind to settle lawsuit.” Los Angeles Times, June 6, 2007; Daniel Yi, “MannKind’s hopes rest with its inhaled insulin,” Los Angeles Times, May 21, 2007.

UNC doctor says GlaxoSmithKline threatened to sue him over Avandia criticism

Buse says Avandia may increase risk by 50 percent

When Dr. John B. Buse testified at a U.S. Congressional hearing on June 6, 2007, he explained how a top executive at pharmaceutical giant GlaxoSmithKline (GSK) threatened him with a lawsuit because the doctor warned the public about Glaxo’s drug, Avandia.

Buse’s confrontation with GSK began in 1999, he said, when he told the U.S. Food and Drug Administration that Avandia raised the risk of chest pain and heart attacks by 50 percent. He said he was given 25 minutes to present two hours worth of research at that hearing.

After that hearing, Buse said “an executive,” later tabbed as Dr. Tadataka Yamada, the then-chief of research and development at SmithKline Beecham, called him a “liar” and a “scoundrel” for his research on Avandia.

According to Buse, the company went as far as suggesting to his boss that the doctor wanted to be paid off. Buse wrote in a letter to Yamada in 1999, in which he said “I was not upset when my chairman called me into his office to tell me that some in your company perceive me as being ‘for sale,’ as he knows me well enough to doubt it.”

In addition, GSK suggested Buse might be sued for lost profits. “The market capitalisation of the company had declined by $4 billion and there were people in the company who felt I might be liable for that,” he stated.

Representative John Yarmuth, Democrat from Kentucky, said in the June 6 hearing, “We cannot have a post-regulatory environment where manufacturers intimidate scientists.”

Sources: Stephanie Saul, “Doctor Says He Was Assailed for Challenging Drug’s Safety,” New York Times, June 7, 2007.