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Avandia News
In Europe, Warning on Avandia Is Old News
By Jeanne Whalen
Companies Featured in This Article: GlaxoSmithKline
Concerns about the safety of GlaxoSmithKline PLC's diabetes
drug Avandia underscore the different approaches to medical
regulation in different markets.
A day after U.S. politicians called on the U.S. Food and
Drug Administration to strengthen its warnings on the drug,
Europe's main medical regulator reiterated that it had strengthened
warnings about Avandia's cardiovascular risks last fall based
on company data available to regulators on both sides of the
Atlantic.
Avandia came under fire Monday after a prominent U.S. cardiologist
published a study in the New England Journal of Medicine linking
the drug to possible heart-attack risks. The U.S. Food and
...
GSK strongly disagrees with conclusions reached in NEJM
article on Avandia
Pharmaceutical News
GSK strongly disagrees with conclusions reached in NEJM article
on Avandia
Tuesday, 22-May-2007 - GSK strongly disagrees with conclusions
reached in NEJM article on Avandia. GlaxoSmithKline has issued
the following response to an article in the New England Journal
of Medicine (NEJM) on Avandia (rosiglitazone maleate), a widely
used and highly effective treatment for type 2 diabetes.
GSK strongly disagrees with the conclusions reached in the
NEJM article, which are based on incomplete evidence and a
methodology that the author admits has significant limitations.
The NEJM paper is based on an analysis of summary information
that combines a number of studies - a meta-analysis - which
is not the most rigorous way to reach definite conclusions
about adverse events. Each study is designed differently and
looks at unique questions: for example, individual studies
vary in size and length, in the type of patients who participated,
and in the outcomes they investigate. The data compiled from
these varied studies is complex and can be conflicting.
Importantly, the editorial in the NEJM states: "A few
events either way might have changed the findings for myocardial
infarction or for death from cardiovascular causes. In this
setting, the possibility that the findings were due to chance
cannot be excluded. In their discussion, the authors properly
emphasize the fragility of their findings."
In contrast to a meta-analysis, the most scientifically rigorous
way to examine the safety and benefits of a medicine is to
conduct large scale, long- term clinical trials in patients
with the disease. Several trials of this type have been ongoing
for many years. To date concerns regarding patient safety
have not been identified by the independent Safety Monitoring
Boards for these trials. Several trials have been completed
and the results published. For example, GSK's long-term, landmark
study 'ADOPT' (A Diabetes Outcome Progression Trial) - one
of the longest clinical trials in people with type 2 diabetes
to date - directly compared both the safety and effectiveness
of Avandia with other oral anti-diabetic medicines in over
4,300 patients studied for up to 6 years.
Data from ADOPT showed that the overall risk of serious,
cardiovascular events (CV death, myocardial infarction, and
stroke, or MACE endpoint) for patients on Avandia was comparable
to metformin and sulfonylurea (glyburide) - two of the most
commonly used medicines to treat type 2 diabetes. ADOPT showed
comparable rates of cardiovascular deaths: Avandia - 5 reports
out of 1,456 patients, or 0.34%; metformin - 4 out of 1,454,
or 0.28%; and glyburide - 8 out of 1,441 or 0.56%. The ADOPT
clinical trial did show a small increase in reports of myocardial
infarction among the Avandia-treated group (Avandia: 24 out
of 1,456 or 1.65%) vs metformin (20 out of 1,454 or 1.38%)
vs glyburide (14 out of 1,441 or 0.97%); however, the number
of events is too small to reach a reliable conclusion about
the role any of the medicines may have played in this finding.
Importantly, ADOPT also demonstrated that Avandia was superior
to metformin and sulfonylurea regarding long-term control
of blood sugar over five years, which is a key goal in managing
diabetes to avoid the long-term complications of the disease.
In another long-term study, DREAM - which followed over 5,200
patients at high risk of developing of type 2 diabetes for
a period of three to five years - Avandia monotherapy showed
no increase in cardiovascular risk when compared to placebo.
Furthermore, in 2000, GSK initiated RECORD - a large, long-term
clinical trial in people with diabetes- which has been prospectively
designed to look at cardiovascular outcomes. The independent
Safety Monitoring Boards responsible for overseeing the safety
of this trial monitors patients closely, and in its regular
operations has not found any safety risk that would interrupt
continuation of the study.
In addition, in a comprehensive analysis of patients in a
US managed care database of more than 33,000 people with diabetes
- performed by independent investigators - there was no difference
in ischemic cardiovascular events (including myocardial infarction)
among patients taking Avandia-containing regimens versus other
oral anti-diabetic medicines.
The totality of the data show that Avandia has a comparable
cardiovascular profile to other oral anti-diabetic medicines.
GSK stands firmly behind the safety of Avandia when used appropriately,
and we believe its significant benefits continue to outweigh
any treatment risks.
Because Avandia has been shown to control blood sugar for
longer than other standard oral anti-diabetic medicines, it
is an important treatment option for physicians who often
need to prescribe two or three medicines to help their patients
maintain their blood sugar levels. Type 2 diabetes is chronic,
relentlessly progressive and life threatening; yet, two-thirds
of diabetic patients suffer with uncontrolled disease. If
left uncontrolled, diabetes can lead to heart disease, and
is the leading cause of blindness, kidney disease and non-traumatic
amputations in the US.
GSK has consistently shared its data on Avandia from meta-analyses
and controlled studies with the FDA and other regulatory agencies.
Data is also posted publicly on the company's Clinical Trial
Register. We continue to work closely with regulatory authorities
and physicians to keep them fully informed so they can make
the best decisions for patients based on both the safety and
benefit of the medicine.
http://www.gsk.com/
Bill calls for FDA to end all conflicts of interest
Agency faces pressure on advisers who have financial ties to firms
By Diedtra Henderson, Globe Staff
August 7, 2007 - WASHINGTON -- The Food and Drug Administration could face a tough new assignment from Congress: Eliminate all conflicts of interest on outside advisory panels whose votes heavily guide the agency's decision-making.
US Representative Maurice Hinchey, Democrat of New York, attached such language to an agriculture appropriations bill passed by the House last week. The funding measure next moves to the Senate, where the FDA conflicts section faces a tough fight; opponents include Senator Edward M. Kennedy, Democrat of Massachusetts.
Regardless of the Hinchey proposal's fate, such congressional chatter might trigger the FDA to act forcefully on its own.
Under congressional pressure, the agency said earlier this year that it intends to bar advisers with financial ties to drug and medical device companies that exceed $50,000. Even researchers whose grants or consulting fees amount to less than $50,000 during the previous 12 months would be affected under the draft guidance; they would be allowed to serve as FDA advisers but could not vote on the meeting's outcome. The FDA is still sifting public comments and has not issued a final proposal.
The moves come amid unprecedented attention to the billions of dollars in drug industry funding that flow through academia and the nation's top hospitals. Because so many leading researchers accept drug and device company funding, the FDA has said it has a difficult time eliminating all traces of financial ties among its advisers. Often it can't find enough scientists free of conflicts within the FDA or other federal health agencies, such as the National Institutes of Health and the Centers for Disease Control and Prevention. The FDA has argued that it must retain the latitude to grant waivers so the nation's finest scientific talent will be able to serve on advisory panels.
That's a viewpoint endorsed by Kennedy, who noted that doctors Craig Mello and Phillip Sharp, Nobel-Prize-winning Massachusetts sci entists, would face limits on their participation on FDA panels if Senate proponents of the stricter rules were successful.
"Many of the nation's best scientists wear both hats -- working in an academic lab one day and consulting for a start-up biotech firm the next," Kennedy said in May, rejecting a move to impose an "inflexible" cap on the number of waivers the FDA can grant.
Last week, for example, five researchers on the 26-member panel that decided to keep the diabetes drug Avandia on the market had financial ties to GlaxoSmithKline PLC, its manufacturer, or to rival companies.
Dr. John R. Teerlink, director of the heart-failure clinic at the San Francisco Veterans Affairs Medical Center, reported receiving the highest level of funding -- between $10,001 and $50,000 as a reviewer for a drug company that competes with Glaxo and $50,001 to $100,000 in stock held in a health sector mutual fund. Teerlink, permitted to vote by the FDA, agreed with the majority that Avandia's emerging heart attack risks are real, but he also voted to keep the drug on the market.
Dr. Curt Furberg, who also served on the Avandia panel, expects congressional interest will lead the FDA to further refine what it considers to be a conflict of interest. Furberg is paid $200 annually to consult for the NIH on a diabetes study that includes Avandia. The FDA permitted him to serve as a temporary adviser for the Avandia panel but barred him from voting.
Furberg, a drug safety expert at Wake Forest University School of Medicine, and others have argued that the FDA packs panels with clinicians more apt to keep questionable products on the market to help their patients but includes fewer drug safety proponents who argue for restrictions and market withdrawals.
"My assumption is it is going to be tougher to stack the committee with people who have conflicts," Furberg said. "The first step is to limit the number of people with potential conflicts. The other is to define conflict more explicitly."
Diedtra Henderson can be reached at dhenderson@globe.com
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