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Diabetes drugs need cardiovascular risk studies, says FDA panel
 
 
  03 July 2008
www.pharmatimes.com
 
US regulators have been advised by a panel of experts to insist that studies on new diabetes treatments need to include much more data on the potential heart risks of the treatments.
 
The US Food and Drug Administration's Endocrinologic and Metabolic Drugs Advisory Committee has voted 14-2 to recommend that pharmaceutical firms must carry out a long-term study of cardiovascular effects or provide equivalent evidence to rule out what the panel calls an unacceptable risk of heart problems. Such studies would need to last as long as five years to detect heart attacks, strokes etc, said a number of panel members, while a number of them endorsed the idea of completing such studies after a drug reaches the market.
 
The two-day meeting heard from a non-voting panel member, Steven Nissen of the Cleveland Clinic who said that "merely lowering blood glucose levels in diabetes is too simplistic. We must reduce the complications of diabetes, including cardiovascular disease". Dr Nissen was the author of the controversial meta-analysis published over a year ago in the New England Journal of Medicine which claimed that users of GlaxoSmithKline's Avandia (rosiglitazone) experienced increased cardiovascular risks.
 
These latest recommendations are unlikely to go down well with the pharmaceutical firms who are developing new treatments for diabetes as they would inevitably led to more studies and increased costs. However John Jenkins, director of the FDA's Office of New Drugs, said that it involves "a shift in expectations of what we are asking for". It is a higher level of assurance, he said, "that you've excluded cardiovascular risks."
 
Panel member Clifford Rosen, an endocrinologist at the Maine Center for Osteoporosis, acknowledged that "although it might be a little more burdensome...we need more studies". The FDA will decide what restrictions are to be put on drugmakers soon and it usually follows panel recommendations.
 

FDA Panel Urges Upgrade _Of Diabetes-Drug Standards
 
By JARED A. FAVOLE
Wall St J
July 3, 2008
 
A Food and Drug Administration panel of outside medical experts Wednesday said the agency should raise standards for approving diabetes drugs, a move that could affect the $5 billion-plus diabetes drug market in the U.S. The panel recommended the FDA require that companies conduct long-term studies in order to rule out cardiovascular risks, the No. 1 killer of diabetics. Most panel members leaned toward requiring that companies start the studies before the drug is approved and complete them after approval, a move suggested by a prominent cardiologist and frequent FDA critic, Steven Nissen of the Cleveland Clinic.
 
The FDA doesn't have to follow its panels' advice, but generally does. "The most important thing they were saying is, 'Yeah, you need cardiovascular outcome data,"' said Robert Temple, director of the FDA's office of medical policy. The panel stopped short of saying new diabetes drugs should show a benefit to patients' cardiovascular health, citing FDA evidence that no diabetes drug has shown such a benefit. "Showing cardiovascular benefit would be nice to know," panel member and physician Jessica W. Henderson said. "But ruling out cardiovascular risk is a need-to-know" requirement for approval.
 

FDA panel urges more testing for diabetes drugs
 
By MATTHEW PERRONE
WASHINGTON (AP) - Diabetes drugs should face tougher safety standards that could cost manufacturers millions but protect patients from unforeseen heart risks, a government panel has recommended.
 
Advisers to the Food and Drug Administration voted 14-2 on Wednesday that all new diabetes drugs should undergo longer studies to assure they don't increase risks of heart problems. The agency currently doesn't screen for heart risks associated with diabetes drugs.
 
The opinions from diabetes experts, cardiologists and statisticians come less than a year after the FDA was criticized for its handling of heart risks connected with a widely used GlaxoSmithKline pill. The drug was approved in 1999 but the agency didn't add a warning about potential heart risks until last November.
 
The majority of the panel said drug companies could begin safety testing before they submit drugs to the FDA, and finish the studies after the drugs are on the market. The testing would take an estimated five to seven years to complete, and likely cost tens of millions of dollars.
 
At least one panelist doubted whether the proposed studies would actually uncover heart risks, and added they could delay important medical breakthroughs.
 
"If you wait this amount of time for testing you're going to be preventing certain drugs from getting out there that may be better than what we already have," said Dr. Eric Felner, a pediatric specialist at Emory University School of Medicine.
 
The FDA is not required to follow the panel's advice, though it often does.
 
GlaxoSmithKline PLC, AstraZeneca and Novartis AG are among the companies developing diabetes treatments to compete in the domestic market, which grew to more than $6 billion last year, according to pharmaceutical research firm IMS Heath.
 
Takeda Pharmaceuticals' Actos, GlaxoSmithKline's Avandia, and Eli Lilly and Amylin Pharmaceutical's Byetta currently dominate the U.S. market.
 
Nearly 24 million Americans have Type 2 diabetes, which can lead to kidney failure, blindness and heart disease.
 
The FDA was pressured to reconsider how it approves diabetes medications after an analysis released last year showed GlaxoSmithKline's blockbuster drug Avandia may increase patients' risk of heart attack.
 
The agency currently approves diabetes drugs based on their ability to lower blood sugar. But Dr. Steven Nissen, who authored the analysis on Avandia, said Tuesday that criterion has little value if drugs also increase heart problems.
 
Nissen, the chairman of cardiology at the Cleveland Clinic, said the FDA is operating under "the irrational belief that lowering blood sugar using virtually any pharmacological means will produce" better results for patients.
 
He recommended the FDA require drug companies to prove their drugs do not have significant heart risks before granting approval.
 
"The fallacy here is that we will never know everything we'd like to about a drug before it goes on the market," Dr. Ray Woosley, president of the Critical Path Institute in Tucson, Ariz., said in a phone interview Tuesday. "If we held up drugs until we did know everything a lot of people would die."
 
Tougher U.S. rules for diabetes drugs debated
Tue Jul 1, 2008 5:24pm EDT
 
By Lisa Richwine__SILVER SPRING, Md., July 1 (Reuters) - Drug makers should do more testing to see if proposed new diabetes medicines may damage patients' hearts, a prominent cardiologist told a U.S. advisory panel on Tuesday.__
 
Other experts warned that tough standards could stifle development of new treatments by requiring longer and more expensive clinical trials. The U.S. market for the top-selling diabetes medicines now exceeds $6 billion.__
 
"We have to rule out some level of harm prior to approval," Cleveland Clinic cardiologist Steven Nissen told a panel of experts that advises the Food and Drug Administration._
 
_Nissen co-authored an analysis last year that found patients who took GlaxoSmithKline's (GSK.L: Quote, Profile, Research, Stock Buzz) pill Avandia had a higher chance of having a heart attack.__
 
Another government-funded study found diabetics given intensive therapy to lower blood sugar died at a higher rate than others who were allowed a higher blood sugar level. It said no one drug was to blame.__
 
Both studies raised questions about the FDA's current standard for judging diabetes drugs. Companies generally need to show only that the drugs control blood sugar.__
 
The FDA, criticized for its oversight of Avandia and other drugs, is asking the panel of outside experts how much data to demand on cardiovascular effects for new and already approved diabetes drugs.__
 
Recommendations are expected from the panel on Wednesday. The agency usually follows its panels' advice.__
 
Nearly 24 million Americans have diabetes, the U.S. government estimates. Most cases are type 2 diabetes, which experts link with obesity, poor diet and lack of exercise.__
 
Diabetics produce less insulin, or their bodies use it less effectively, which makes blood sugar rise. That can damage blood vessels and organs, leading to blindness, kidney disease, limb loss and heart disease.__
 
Experts agree blood-sugar control helps prevent complications such as damage to the eyes and kidneys. But no conclusive evidence exists that any diabetes drug reduces heart disease, the top killer of diabetics, FDA officials said.__
 
The agency will request a long-term trial on heart risks if mid- and late-stage testing raises concern, Hylton Joffe, lead medical officer in the FDA's diabetes drug group, said. The question remains if all diabetes drugs need cardiovascular testing to show they benefit the heart, or do not harm it.__
 
That requirement would "set a very high hurdle that would affect the availability of new drugs," Joffe said.__
 
Nissen, a vocal FDA critic, said the agency should make companies collect enough data to rule out a certain level of cardiac harm before approval. The FDA also should mandate that companies start a long-term study of heart-related effects before they can sell a new medicine, he said.__
 
The proposal could "modestly" slow a drug's path to the market by about six to 12 months, Nissen said.__
 
"We can still get drugs to patients in a speedy fashion," he said.__
 
Diabetes medicines are among the biggest sellers. U.S. sales of the leading drugs exceeded $6 billion in 2007, according to healthcare information company IMS Health.__
 
The top sellers include Glaxo's Avandia and Takeda Pharmaceutical Co's (4502.T:Quote, Profile, Research, Stock Buzz) rival Actos.__
 
Merck & Co Inc's (MRK.N: Quote, Profile, Research, Stock Buzz) Januvia and Eli Lilly (LLY.N: Quote, Profile, Research, Stock Buzz) and Amylin Pharmaceuticals Inc's (AMLN.O: Quote, Profile, Research, Stock Buzz) Byetta are newer drugs that have gained market share recently.__
 
Glaxo has said Avandia's safety is comparable to similar pills. The company agreed to add a strong warning, however, that the drug might increase heart attack risk with a note that the data is inconclusive. Studies of cardiac effects are continuing. (Reporting by Lisa Richwine; editing by Tim Dobbyn)
 
 
 
 
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