November 24, 2008
Avandia associated with increased mortality
The New York Times reports today that a new study published in The Archives of Internal Medicine found that Avandia (the drug also known as rosiglitazone) was linked to a higher rate of mortality than a similar drug sold under the brand name Actos (also known as pioglitazone). This was an observational study, and representatives of GlaxoSmithKlein criticized it for being inconsistent with and not being as rigorous as randomized clinical trials they conducted. Read more about the study and the reactions of the president of the American Diabetes Association, the consumer watchdog group Public Citizen (which is calling for the drug to be taken off the market) and GlaxoSmithKlein here.
March 27, 2008
FDA Drug Approval Near Deadline Linked to Safety Problems
Article in the Wall Street Journal -- Late Drug Approval Linked To Safety Issues, by Keith J. Winstein. Here's an excerpt:
Although every unsafe drug is different, most of them have something in common: last-minute approvals by the Food and Drug Administration, according to a new study.
Liver problems led Pfizer Inc. to withdraw its diabetes drug Rezulin from the U.S. market in 2000. Bayer AG pulled cholesterol-lowering Baycol in 2001 because it caused muscle damage in some patients. Vioxx, Merck & Co.'s controversial painkiller, was withdrawn in 2004 because it sometimes caused heart attacks and strokes.
These and other unsafe drugs all received approval shortly before the FDA deadline for deciding on new-drug applications.
Since 1993, the 97 drugs approved near the FDA's deadline had a 14% rate of severe safety problems down the road, compared with 3% for 216 other drugs. That's according to an analysis in Thursday's issue of the New England Journal of Medicine by Daniel Carpenter, a professor of government at Harvard University. The FDA says some of Dr. Carpenter's data are inaccurate, and disputed his conclusions.
December 02, 2007
Research Suggests Avandia May Increase Bone Thinning
Article on cnn.com -- Glaxo's Avandia may increase bone thinning. Here's an excerpt:
The popular diabetes drug marketed as Avandia may increase bone thinning, a discovery that could help explain why diabetics can have an increased risk of fractures.
New research raises the possibility that long-term treatment with rosiglitazone, as Avandia is also called, could lead to osteoporosis. The diabetes drug is used to improve response to insulin.
While bones seem solid, they constantly are being broken down and rebuilt by the body. Researchers found that in mice, the drug increased the activity of the cells that degrade bones, according to a report in this week's online issue of Nature Medicine.
Avandia recently was labeled with warnings about the risk of heart failure in some patients. GlaxoSmithKline (Charts), which markets the drug, already has acknowledged that a study found a higher risk of fractures among women who take the drug. But this report is the first to attempt to explain the link between the drug and fractures.
November 17, 2007
Senate Report Criticizes Glaxo's Treatment of Physician Raising Avandia Concerns
Article in the Wall Street Journal -- Glaxo's Handling of Physician Criticized, by Jeanne Whalen. Here's an excerpt:
Over a period of several years, drug maker GlaxoSmithKline PLC was so concerned about a prominent physician's negative views of its diabetes drug that it engaged in a concerted effort to intimidate him and stifle his opinion, a report by the U.S. Senate Finance Committee found.
The report offers a window into the rarely acknowledged practice among drug companies of monitoring and seeking to influence the opinions of leading physicians, who can make or break a drug's sales. The report alleges that Glaxo Chief Executive Jean-Pierre Garnier and former research chief Tachi Yamada were involved in the intimidation.
The Senate Finance Committee released the report Thursday, after researching Glaxo's relationship with 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, one of Glaxo's top selling drugs.
October 24, 2007
Glaxo to Cut Jobs Because of Avandia Problems
Article in the Wall Street Journal -- Glaxo to Cut Jobs As Generics Hit Sales, Profit, by Jeanne Whalen. Here's an excerpt:
GlaxoSmithKline PLC became the latest drug company to announce layoffs and cost cuts after competition from generic medicines and sharply lower sales of the diabetes drug Avandia hurt third-quarter earnings.
The world's second-largest pharmaceutical company by sales said it would take a £1.5 billion ($3.08 billion) charge as part of cost cuts that it estimates will save the company £700 million a year by 2010. Glaxo Chief Executive Jean-Pierre Garnier said layoffs would be involved, but he declined to say how many.
Glaxo, based in Brentford, England, was particularly hard hit by plummeting sales of Avandia, a once-popular diabetes drug now linked by some research to heart-attack risks.
August 17, 2007
Black Box Warnings for Avandia and Actos
Article on cnn.com -- Avandia, Actos to include 'black box' warnings, by the Associated Press. Here's an excerpt:
The diabetes drugs Avandia and Actos will be labeled with severe warnings about a risk of heart failure to some patients, health officials said Tuesday.
The makers of the drugs, GlaxoSmithKline Plc and Takeda Pharmaceutical Company Ltd., have agreed to add the "black-box" warnings, the Food and Drug Administration said. The warnings, the most severe that prescription drugs can bear, stress the medicines may cause or worsen heart failure and that patients should be closely monitored.
The warnings also apply to combination drugs that include the active ingredients in Avandia, made by Glaxo, or Takeda's Actos. The drugs help patients with Type 2 diabetes control their blood sugar levels.
July 31, 2007
FDA Advisory Panel for Avandia Votes, Finds Heart Risk
Article in the Wall Street Journal -- Panel Keeps Avandia on Market: Glaxo's Diabetes Drug May Require Warning On Label for Heart Risks, by Anna Wilde Mathews. Here's an excerpt:
A Food and Drug Administration advisory committee found that GlaxoSmithKline PLC's diabetes drug Avandia is tied to a risk of heart attacks, but it stopped short of voting to pull the medication off the market.
Several panel members said the drug should get a new heart-risk warning in its label, which would be a blow to the company but far less serious than a recommendation to end sales of Avandia. Last year, it was the company's second-biggest-selling drug with global sales of $3.38 billion, and it has been used by more than seven million patients world-wide.
The heart-risk warning is likely to accelerate the reshuffling of the growing market for diabetes drugs, boosting sales of older medications and Takeda Pharmaceutical Co.'s Actos, the only marketed rival that works the same way as Avandia. So far, Actos hasn't been linked to a heart-attack risk. The FDA doesn't have to follow the advice of its expert panels, but it typically does. An agency official said after the meeting that the FDA would aim to reach a decision quickly.
July 27, 2007
Upcoming FDA Advisory Panel Meeting on Glaxo's Avandia
Article in the Wall Street Journal -- FDA to Seek Guidance Over Avandia, by Jennifer Corbett Dooren and Anna Wilde Mathews. Here's an excerpt:
The Food and Drug Administration is concerned about the potential heart-attack risk tied to the widely used GlaxoSmithKline PLC diabetes drug Avandia, and the agency will ask an advisory panel whether the medication should remain on the U.S. market.
In documents made public yesterday in advance of a public meeting set for Monday, FDA officials wrote that they view Avandia's potential heart-attack risk with "considerable concern," despite "somewhat inconsistent findings that complicate the interpretation of the available data." They wrote that "it is also important to place any risk into context of what is known about the risks of other available therapies" -- notably Japan's Takeda Pharmaceutical Co.'s Actos, the only marketed diabetes drug that works the same way as Avandia.
Monday's meeting could be as significant for the Takeda medication as it is for Avandia. In January, Avandia had 51% while Actos had 49% of the U.S. market for their class of drugs, according to a Morgan Stanley research report that cites data from IMS Health. In May, the New England Journal of Medicine published an analysis by Cleveland Clinic cardiologist Steven Nissen linking Avandia to a potential risk of heart attacks. By July 13, Avandia's market share had dropped to 33% and Actos had soared to 67%. Last year, Avandia was Glaxo's second biggest-selling drug with global sales of $3.38 billion, making up 7% of the Brentford, England, company's total sales of $47.63 billion.
July 26, 2007
Glaxo Maintains Profit Outlook Despite Avandia Concerns
Article in the Wall Street Journal -- Glaxo, Set Back By Diabetes Drug, Sticks to Forecast, by Elena Berton. Here's an excerpt:
Sales for the Avandia family of drugs, which also include combination products Avandamet and Avandaryl, fell 22% to £349 million. Avandia has been hit by concerns about possible cardiovascular side effects linked to the drug. The company has mounted a robust defense of its second best-selling product, releasing data from studies that appear to back Avandia's safety.
A Food and Drug Administration panel of experts is scheduled to meet next week to decide whether Avandia should remain on the market and, if so, whether its use should be further restricted. Chief Executive Jean-Pierre Garnier said Glaxo has submitted to the U.S. regulator new data from an epidemiology study on 400,000 diabetes patients, which supports the safety of the drug.
May 27, 2007
Sen. Grassley Says FDA Study Also Shows Avandia Risk
Article in the Washington Post -- FDA Study Said to Show Avandia Risk, by Marilynn Marchione. Here's an excerpt:
The government's own preliminary evaluation of the diabetes pill Avandia confirms the heart risks reported in a study earlier this week and suggests that as many as 60,000 to 100,000 heart attacks might be linked to its use since it came on the market eight years ago, a leading member of Congress said Thursday.
In a floor statement placed in the Senate record, Sen. Charles Grassley also said that safety watchdogs within the federal Food and Drug Administration "several months ago" recommended a "black box" on the drug's label _ the strongest possible warning.
It is the first confirmation that the FDA's own analysis of Avandia shows a similar magnitude of heart attack risks _ dangers that were first publicly raised in a medical journal report published earlier this week.
Grassley complained that FDA higher-ups have said they want to wait for results of an ongoing study that will not be available for two more years before making a decision.
May 26, 2007
Glaxo's Large Avandia Clinical Study In Question Because of Patients Dropping Out
Article in the New York Times -- Test of Drug for Diabetes in Jeopardy, by Stephanie Saul. Here's an excerpt:
A large clinical study meant to test the heart safety of the diabetes treatment Avandia may be in jeopardy as a result of recent reports of the drug’s risks, according to an executive for its maker, GlaxoSmithKline.
Dr. Ronald L. Krall, the medical director for GlaxoSmithKline, said in a telephone interview yesterday that some of the 4,450 patients enrolled in the drug trial, called Record, have dropped out this week because of safety concerns about Avandia.
Dr. Krall said he did not yet know how many patients have withdrawn, but said Glaxo was now worried about whether it could complete the drug trial, which has been scheduled to run through next year. The company has been counting on a successful outcome from the study to dispel widespread concerns that Avandia carries a higher risk of heart attacks than other diabetes drugs.
Now, though, the independent research committees overseeing the study “are concerned about the ability of the study to continue” and are “considering what to do to prevent people from dropping out of the trial,” Dr. Krall said.
May 25, 2007
Glaxo Courts Doctor Support for Diabetes Drug Avandia
Article in the Wall Street Journal -- Glaxo Courts Doctor Support of Avandia: No Plans Currently Set To Run Consumer Ads To Defend Drug's Safety, by Jeanne Whalen and Anna Wilde Mathews. Here's an excerpt:
GlaxoSmithKline PLC, under pressure to protect its diabetes drug Avandia, is reaching out to physicians to defend the drug's safety, but isn't currently planning a similar ad campaign for consumers.
In meetings with doctors, Glaxo sales representatives are focusing on data from a large clinical trial called A Diabetes Outcome Progression Trial, or ADOPT. "We are reassuring physicians about the safety data we have, particularly looking at ADOPT," said Alice Hunt, a Glaxo spokeswoman.
Monday, the New England Journal of Medicine released an analysis by Cleveland Clinic cardiologist Steven Nissen linking Avandia to a potential risk of heart attacks. Glaxo disagrees with the finding, which it says is contradicted by data the company considers stronger, including ADOPT data.
Congressional investigators are examining the Food and Drug Administration's and the company's handling of the drug. Yesterday, Republican Sen. Charles Grassley of Iowa said that the FDA's division of drug-risk evaluation had recommended a tough "black box" warning about heart-attack risk for the label of Avandia, which hasn't been added. He and Senate Finance Committee Chairman Max Baucus, a Montana Democrat, introduced a bill that would grant researchers access to Medicare data on medical treatments.
May 23, 2007
Glaxo's Agreement to Disclose Publicly Clinical-Trial Results Lead to Finding of Avandia Risk
Article in the New York Times -- For Drug Makers, a Downside to Full Disclosure, by Barry Meier. Here's an excerpt:
When GlaxoSmithKline settled a lawsuit three years ago with the State of New York over the antidepressant medication Paxil, the company agreed to take an unusual step: publicly disclosing the results of its clinical trials for Paxil and other drugs.
The company, which was criticized at the time for failing to publicize all pediatric trials of Paxil, not just the positive ones, made good on its promise. The first posting on a new Web site was about 65 studies involving its popular diabetes drug, Avandia.
This week, GlaxoSmithKline learned what that greater disclosure could mean.
A cardiologist at the Cleveland Clinic, Dr. Steven Nissen, stumbled onto the Glaxo Web site while researching Avandia last April. He and a colleague quickly analyzed the data, and on Monday, The New England Journal of Medicine released its finding that Avandia posed a heightened cardiac risk.
“It was a treasure trove,” Dr. Nissen said about the Web site.
Concerns About Glaxo Drug Avandia and PPAR Drugs
Article in the Wall Street Journal -- Avandia Concerns Reopen a Wider Debate, by Anna Wilde Mathews and Jeanne Whalen. Here's an excerpt:
The assertion that GlaxoSmithKline PLC's widely used diabetes drug Avandia is tied to a risk of heart attacks will reopen debate over a potentially valuable, but problem-plagued, type of drugs.
Avandia and the competing diabetes medication Actos, made by Japan's Takeda Pharmaceutical Co., are known as PPAR drugs. They work by affecting receptors in a cell's nucleus that can affect a broad range of human genes. (PPAR represents the name of the receptors, which are called peroxisome proliferator-activated receptors.)
The upshot can be valuable treatment benefits for serious conditions such as diabetes but also an enormous range of sometimes unpredictable side effects that have sidelined many treatments before they reached the market. Among the companies still working on possible new PPAR drugs are Glaxo, AstraZeneca PLC and closely held Metabolex Inc., which has partnered with Johnson & Johnson.
"It is a challenging class of drugs," said Robert Meyer, who heads the Food and Drug Administration office that oversees diabetes medications. "These are drugs with many effects and many targets" in the body.
May 22, 2007
Prominent Doctor Publishes Study Showing Heart Risk from Glaxo Diabetes Drug Avandia
Article in the Wall Street Journal -- Sequel for Vioxx Critic: Attack on Diabetes Pill: Glaxo Shares Plunge As Dr. Nissen Sees Risk To Heart From Avandia, by Anna WIlde Mathews. Here's an excerpt:
An analysis linking the widely used diabetes drug Avandia to higher risk of heart attacks represents a serious blow to GlaxoSmithKline PLC and underscores how outside critics have been empowered to challenge big-selling drugs after the outcry over the withdrawn painkiller Vioxx.
Glaxo rang up more than $3 billion in world-wide sales of Avandia last year. Its share price fell more than 7% after the New England Journal of Medicine released the analysis by prominent cardiologist Steven Nissen of the Cleveland Clinic, who helped raise early safety concerns about Vioxx. The analysis suggested that people on Avandia have a 43% higher chance of suffering a heart attack.
Glaxo said it "strongly disagrees" with his conclusions, which come from a "meta-analysis" in which results from many trials are combined. Glaxo said data sources it considers more reliable suggest that Avandia is no riskier for the heart than other diabetes medications.
Here's a link to the related article in the New England Journal of Medicine -- Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes, by Steven E. Nissen, M.D., and Kathy Wolski, M.P.H.; and a link to the related New England Journal of Medicine editorial --
Rosiglitazone and Cardiovascular Risk, by Bruce M. Psaty, M.D., Ph.D., and Curt D. Furberg, M.D., Ph.D.