AvandiaGate: The FDA Panel Will Meet July 30
4 CommentsBy Ed Silverman // June 5th, 2007 // 12:09 pm
A lot of folks will need their scheduled vacation after this one. Reuters is reporting that the FDA has scheduled the date to convene two - count ‘em, two - advisory committees to discuss the cardivascular risks of Avandia.
The endocrine and metabolic drugs committee and the drug safety and risk management committee will meet simultaneously.
Absent the heated political rhetoric that’s certain to be heard at tomorrow’s Congressional hearing, this promises to be just as fascinating. You can almost hear the sparring between Glaxo scientists, academic researchers and FDA staffers now.
Meanwhile, the drugmaker is reading from the crisis playbook - last week, execs appeared before cameras looking solemn and speaking assertively about Avandia safety risks. Then there was the letter to The Lancet. And today, Glaxo takes out well-timed, full-page ads in various newspapers to reassure the public that it stands behind the safety of Avandia. The drugmaker wouldn’t say how much it spent, but a spokeswoman for The New York Times tells Reuters it charges $110,000 for a full-page ad.
Investors, however, aren’t moved. Pressure is mounting for Glaxo, which has already increased debt and its share buyback program, to boost its dividend or sell off one of its businesses, perhaps consumer healthcare or the soft-drink unit (that’s the one that sold Ribena without the advertised vitamin C).
Dr. Remulac
Hopefully the panel will broaden the scope of this to include all PPAR agonists, including Actos and drugs like Tricor that are PPAR-alpha agonists. There was a little media activity around Tricor Sun/Mon due to the Barron’s piece, which was a bit off-focus with it’s emphasis on rises in serum creatinine on Tricor (this has been long known), and it’s provocative comment attriubuted to Steve Nissen that he “won’t prescribe this drug”. The real issue with Tricor is found in the full results of the FIELD trial, and Abbott’s behavior relating to that study. Citigroup issued a report yesterday on the subject of an updated analysis of that trial published as a simple letter in the Lancet back in October of 2006. (By the way, the primary endpoint was not met in this trial, and Abbott has engaged in programmatic cherry-picking of secondary endpoints) In this analysis, they found that the risk of cardiovascular events was 27% to 106% (!!) higher among patients on the combination of a statin plus Tricor versus those on monotherapy. Since most patients with diabetes should be on a statin these days per NCEP, ADA, and AHA prevention guidelines, this is particuarly troublesome. Given that this is data from a prospective clinical trial, with about 2500 patients treated for 3-5 years making up this subanalysis, this is rather serious. It is certainly more impactful and scientifically meaningful than a seriously flawed meta-analysis with about 6 months of follow-up that put Avandia in hot water! Even more damning has been Abbott’s behavior and treatment of this information. Abbott has conducted a huge amount of promotion/marketing/medical education around the FIELD trial, but they have never acknowledged this updated information in any way, shape, or form. So much for fair balance and complete disclosure! The entire group of PPAR agonists (alpha and gamma included) needs to be scrutinized, and companies like Takeda and Abbott must be held to the same scrutiny as GSK has been. Hell, at least Glaxo voluntarily submitted less-than-positive information to the FDA in form of their own meta-analysis last year. What has Abbott, and for that matter Takeda, done???
Dr. Remulac
Boy, no sooner than I post my original comment, this comes out. CHF is a very well-known complication of TZD therapy, and has also been clearly documented with Actos.
Press Release Source: GlaxoSmithKline
Interim Data From RECORD Study Show No Significant Difference Between Avandia and Standard Therapy in Risk of Cardiovascular Hospitalization or Death
Tuesday June 5, 3:15 pm ET
“Patients and physicians should find these data reassuring”
PHILADELPHIA, June 5 /PRNewswire-FirstCall/ — GlaxoSmithKline (NYSE: GSK - News) said today that findings from an interim analysis of RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycemia in Diabetes), a prospective clinical trial designed specifically to determine cardiovascular outcomes in more than 4,400 patients with type 2 diabetes, adds further evidence to the overall cardiovascular safety profile of Avandia® (rosiglitazone maleate). The study results, authored by Philip D. Home and colleagues on the RECORD Steering Committee, were published Tuesday in the online edition of The New England Journal of Medicine.
The study compares cardiovascular hospitalization and death in patients treated with Avandia dual therapy (Avandia plus metformin or sulfonylurea) and in patients treated with metformin and sulfonylurea in combination. After following patients for an average of 3.75 years, the interim analysis found a low number of events overall, and a similar number of events in each group. The study is scheduled to complete in late 2008.
Like all interim analyses, these data do not offer final conclusions. Based on the interim analysis, key findings include:
— The interim data show no significant difference between the Avandia and
control groups in the key outcomes of hospitalization or death due to
cardiovascular events.
— There was no difference between the groups in mortality, whether
cardiovascular deaths or deaths from all causes.
— The interim data show that Avandia was not significantly different than
the control groups in several secondary outcomes, including heart
attack.
— A significant difference between the Avandia and control groups was
seen only in the secondary outcome of congestive heart failure (CHF),
where significantly more cases were seen in Avandia patients -
consistent with the well known association between fluid retention and
TZDs, the class of medicine to which Avandia belongs. Fluid retention
can worsen or lead to CHF. Importantly, despite the increase in CHF,
there was no difference between the Avandia group and the control
groups in the key outcome of cardiovascular hospitalizations and death.
“The interim findings do not show evidence of a significant difference in cardiovascular death and heart attack between Avandia and the control groups, and therefore do not confirm the hypothesis generated by the recently published meta-analysis in the New England Journal of Medicine that raised concerns about these events with Avandia,” said Moncef Slaoui, chairman, R&D for GSK. “They add to the weight of evidence, from both previously published long-term clinical trials and other studies, that the overall ischemic cardiovascular safety profile of Avandia is comparable to the traditional anti-diabetes treatments. Patients and physicians should find these data reassuring.”
Because Avandia has been shown to control blood sugar for longer than other traditional oral anti-diabetic medicines, it is an important option for physicians who often need to prescribe a combination of diabetes medicines to help their patients maintain blood sugar levels.
Professor Home, Vice President, International Diabetes Federation, University of Newcastle-upon-Tyne, UK, and chairman of the RECORD Steering Committee, said that although the study is not expected to be complete until late 2008, the committee concluded that an interim analysis should be published as soon as possible. “Ideally, we would have allowed RECORD to complete before analyzing and releasing the results,” Home said. “However, in light of the questions raised recently about Avandia, we felt it critical that interim data from this important study be made available to physicians and patients immediately so that treatment decisions may be based on all the available evidence.”
Richard Nesto, MD, Chairman of the Department of Cardiovascular Medicine at the Lahey Clinic Medical Center, said these new findings provide important information for physicians caring for diabetic patients. “Despite its limitations, the recent meta-analysis in the New England Journal of Medicine raised important questions about the cardiac safety of rosiglitazone. These questions can only be answered with better evidence from clinical trials. This interim analysis of RECORD, a randomized prospective clinical trial, helps to establish the overall cardiac safety profile of the drug,” said Dr. Nesto, who is an author of the American Heart Association and American Diabetes Association consensus statement on the use of thiazolidinediones in diabetic patients with heart disease. “Additional clinical trials are underway to specifically address this issue, but the data from RECORD should be reassuring for physicians who need effective drugs to lower blood sugar levels — the main cornerstone of treatment for diabetic patients.”
The RECORD study’s robust design and breadth make it uniquely suited to answer questions about cardiovascular risk with Avandia.
First, the study was designed to include a wide range of Type 2 diabetes patients, including those with and without existing cardiovascular disease, making it highly representative of real-world diabetes patients. Second, patients in RECORD were managed such that blood sugar remained within current guidelines, thereby eliminating a variable that may affect results, as inadequate blood sugar control is itself associated with cardiovascular events. Third, although an open-label design, each cardiovascular event was verified by an independent panel of physicians who did not know which medicines the patients were taking.
Under these rigorous standards, the interim analysis shows that the incidence of cardiovascular hospitalization and death were comparable for the patients taking the Avandia combination and the patients taking the metformin-sulfonylurea combination
[e-PHARMArketing.com]
Avandia, communication de crise aux US…
Pour les blogueurs pharma US, il s’agit déjà d’un Avandiagate. Avec toute la dramaturgie voulue… Pour vous faire une idée regardez les 1028 références (aujourd’hui) que ramène une recherche Google avec AvandiaGate
Une viei…
Avandia, communication de crise aux US | [ e-PHARMArketing.com ]
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