FDA Panel: Keep Avandia on Market With Restrictions
By Donna Young
Restricting Avandia's use to certain patients could open up more opportunities for other glycemic-control agents, many of them biotech drugs, which could have a greater opportunity to snatch a share of the Type II diabetes market if the FDA acts on its committee's advice.
Panelist Lamont Weide, chief of diabetes and endocrinology at the University of Missouri-Kansas City, said he expected Avandia prescriptions to decrease. "But I would hate to take it away," he said, voting to leave the drug on the market, but under restrictive conditions.
"We need to have very tight control over the administration of this drug," said panelist Clifford Rosen, director of clinical and translational research at Maine Medical Center Research Institute, who called for a registry to "find out what really is going on with those people and their long-term safety."
But he insisted only endocrinologists should be permitted to prescribe the drug. "This is an opportunity to collect data and restrict the use," Rosen added. Ten of the FDA's outside advisers said Avandia should remain available to U.S. Type II diabetes patients, but with stronger warnings and under certain restrictions. Seven said GSK should continue to be allowed to sell Avandia in the
Three on the committee said the drug's status should remain unchanged. But there were 12 panelists who voted in favor of yanking the drug from the market. "I don't see where this drug needs to be on the market anymore," said panelist Morrie Schambelan, associate chair of clinical and translational research at the
"I haven't heard any evidence of meaningful benefit," said panelist Richard Platt, chair of population medicine at
No one on the panel voted in favor of GSK's proposal to remove from Avandia's black-box warning an alert about myocardial ischemia and the language about the meta-analysis of 42 controlled clinical trials and three long-term controlled studies backing up that risk warning.
The committee also voted 19 to 11 – with two abstentions – that GSK's ongoing prospective outcomes TIDE study assessing the CV risks of Avandia vs. Takeda Pharmaceutical Co. Ltd.'s Actos (pioglitazone) should continue.
TIDE, or Thiazolidinedione Intervention with Vitamin D Evaluation, is an event-driven, multicenter, international, randomized, double-blind, placebo-controlled trial designed to evaluate the effects of Avandia and Actos or placebo added-on to background antidiabetic therapies in about 11,680 patients with Type II diabetes on the time to first occurrence of the primary composite endpoint of CV death, nonfatal MI, or nonfatal stroke. The trial's co-primary objectives are noninferiority comparison of Avandia vs. placebo performed after total follow-up of 4.5 years and superiority of Avandia and Actos vs. placebo performed about one year after the noninferiority comparison.
But TIDE has had difficulty recruiting patients, an outcome co-lead investigator Hertzel Gerstein blamed on the negative "political" reports about the drug.
Platt said he voted against continuation of the trial because it failed to meet the
As predicted, the FDA's newly reconfigured voting system resulted in some chaos Wednesday, with a handful of panelists changing their votes after acknowledging they had pushed the wrong buttons."I meant to vote for Pat Buchannan," said Michael Proschan, a mathematical statistician at the National Institute of Allergy and Infectious Diseases, said in making a reference to
Panelists also were not given the normal "abstain" option for most of the questions, but instead were given the choice of answering that they could not make a finding on the particular question.
Committee members, however, could abstain on the TIDE question by pressing the "D" button. For the marketing question, an abstention was acknowledged by simply not voting, since the voting system only had five buttons. Proschan was the lone abstention from the marketing vote.
Much of the two-day meeting revolved around GSK's RECORD study, which showed that Avandia does not have an increased risk of ischemic CV events. But panelists, for the most part, were unsure about the reliability of the results, with many contending that the trial only added to the confusion about Avandia's CV risks.
The panel voted 18 to 6 that the available data were sufficient to raise significant safety concerns for ischemic CV events in Type II diabetics taking Avandia vs. non-TZD antidiabetic agents, while nine panelists said they were not able to make a finding on that question.
The committee voted 21 to 3 that the available data were adequate to raise significant safety concerns for ischemic CV events in Type II diabetics taking Avandia vs. Actos, with nine again responding that they were not able to come to a definitive conclusion on that question. Panelists were more skeptical on the mortality questions, voting 20 to 1 that the data were insufficient to raise significant safety concerns for death in Type II diabetics taking Avandia vs. non-TZD antidiabetic agents, with 12 panelists responding that they were not able to make a finding on that question.
When it came to comparing Avandia to Actos for safety concerns of death, the panel voted 12 to 7 that the data were insufficient on GSK's drug, but the majority, 14, said they could not make a finding on that question.