As controversy continues to surround GlaxoSmithKline (GSK) and its diabetes drug rosiglitazone (Avandia), the FDA has released hundreds of pages of briefing documents in preparation of FDA committee meetings starting today that will answer questions and hope to settle the ongoing debate whether Avandia does more harm than good.
This week’s committee meetings will be the second surrounding the drug after the FDA in July 2007 concluded that Avandia poses risks (20 to three vote), but could stay on the market (22 to one vote).
Since then, 10 new studies have surfaced, prompting the FDA to further evaluate the safety of rosiglitazone.
“Although the results of RECORD [trial], on their face, would have met the agency’s criteria for evidence that rosiglitazone is not associated with an unacceptably increased risk for major adverse cardiovascular events, there continue to be differences of opinion in this regard," the FDA wrote.
GSK continued to defend Avandia. Within its briefing documents, the company said it has found through the trials that “rosiglitazone has been shown to reduce hyperglycemia and maintain glucose control longer than metformin or sulfonylurean, with no overall increase in CV morbidity and mortality as compared to these agents.”
Additionally in its brief, GSK depicted major cardiac event (MACE) rates for the 52-study meta-analysis as “low” and as being similar between the control arm and the rosiglitazone arm, 0.73 percent versus 0.80 percent, respectively.
GSK admitted that rosiglitazone “is associated with dose related fluid retention,” which could lead to coronary heart failure or edema—information that is currently found as a black box warning on the drug as Avandia is not recommended for patients with symptomatic heart failure.
More questions than answers
In the documents, the FDA sited previous trials that have shown use of rosiglitazone increased the rates of stroke, HF and death, particularly the elderly patient population. "The negative population impact of rosglitazone has probably been great," the documents state.
During Wendesday's portion of the meeting, members will be asked to evaluate the safety of the drug and answer whether present data show Avandia increases cardiac risk.
The committee also will be asked whether or not it recommends that the TIDE (Thiazolidinedione Intervention with Vitamin D Evaluation) trial, an ongoing, prospective trial evaluating the CV risks of rosiglitazone and pioglitazone (Actos; Takeda), should be continued.
The meetings will be a hodge podge of information from variant sources including GSK, Steven Nissen, MD, of the Cleveland Clinic, who will present on the RECORD trial, in addition to Thomas Marciniak, MD, of the FDA’s cardiovascular and renal products division and Ellis Unger, MD, who will also present on the RECORD trial.
On July 14, Hertzel Gerstein, MD, of McMaster University in Hamilton, Ontario, will present on the ongoing TIDE trial that will further study the drug, along with presentations by the Institute of Medicine, followed by an open public forum from 9:40 am to 10:40 am, concluding with a committee vote.