The majority of panelists at an FDA meeting that revisited regulatory decisions made in 2010 recommended relaxing restrictions on the diabetes drug rosiglitazone.
“The [readjudication] results do not remove my concerns about the cardiovascular safety of rosiglitazone,” said Marvin Konstam, MD, chief physician executive at the Cardiovascular Center at Tufts Medical Center in Boston. “But they move the needle in a direction that seems to me is appropriate to shift the burden of decision making for prescribing this drug to the physician.”
Konstam was one of 13 panelists at the meeting to vote in favor of modifying tight restrictions placed on rosiglitazone (Avandia, GlaxoSmithKline) in 2010. The joint meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was assembled to review readjudicated results of RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes). The RECORD trial has been criticized for its open-label design, missing data, potential biases and other limitations. The readjudication process also came under fire from one FDA official who questioned the independence of the Duke Clinical Research institute (DCRI), the contractor who performed the adjudication.
Seven other panelists at the readjudication meeting voted to remove restrictions while five recommended no changes. One member called for withdrawing rosiglitazone from the market.
Several of the panelists who voted to modify restrictions to the risk evaluation and mitigation strategy imposed previously said they wavered between removal and modification of restrictions. The drug had been limited to being a last resort option for patients who don’t respond to other medications.
“The readjudication reconfirmed my uncertainty,” said Sanjay Kaul, MD, director of cardiovascular fellowship training at Cedars-Sinai Medical Center in Los Angeles. I debated between A [removal] and C [modification]. I voted for C because there are some unresolved issues, particularly some of the high-risk subsets, for example, ischemic heart disease.”
Kaul pointed out the potential interaction between drugs commonly prescribed to treat patients with diabetes and an underlying risk for cardiovascular disease. “I think it is a good opportunity to communicate those uncertainties to the patients in a form of a communication plan and medication guidance and to have some process [to]collect information, evaluate and see sudden spikes in the use of rosiglitazone.”
The vote was taken on June 6 at the FDA’s center in Silver Spring, Md. The first day of the meeting included a critical review of RECORD and presentations by the DCRI and FDA officials.
The FDA will consider the panel’s recommendations, which included “a wide range of perspectives on the data. It illustrates that this is not an easy decision on the benefit and risk, given the data and the uncertainties,” according to the FDA. The agency often, but not always, follows the recommendations of its advisory panels.