A controversial 2007 meta-analysis questioning the cardiovascular safety of rosiglitazone opened a Pandora's box for what had been a blockbuster diabetes drug. The story has involved analyses and reanalyses of trial data, accusations of investigator intimidation, FDA and US Senate investigations, black-box warnings, leaked academic papers, accusations of missing data, and wiretapped discussions with the drug manufacturer--all culminating in calls to pull the drug from the market and stop the only trial that might decisively answer the questions that have dogged this drug.
Influenced by a recent RECORD readjudication showing lack of significant harm, a joint FDA advisory panel voted to keep rosiglitazone on the US market and to ease current prescribing restrictions but not remove them entirely.
The first day of a two-day meeting on rosiglitazone included presentations from the FDA, GlaxoSmithKline, Duke University reviewers, and one dissenting FDA official. Today the panel will vote on the drug's future.
A new meta-analysis of observational studies shows rosiglitazone to be associated with a higher risk of heart failure, MI, and death than pioglitazone. But despite having been taken off the market in Europe, the REMS restriction for rosiglitazone recommended by the US FDA last September has still not been finalized.
Physicians who may have seen a sweeping ad campaign unleashed by Takeda when FDA advisors delivered their mostly negative view of rosiglitazone last year should consider other drug classes or lifestyle changes, rather than defaulting to pioglitazone, a new paper argues.
The new label has been changed to highlight the increased cardiovascular risks with the drug, noting that in a meta-analysis of 52 studies, most of which compared rosiglitazone with placebo, the drug was associated with a significantly increased risk of MI.
Regulators from various agencies, including the European Medicines Agency, explain their September 2010 decision to suspend marketing authorization for rosiglitazone in a paper that highlights what evidence was considered in that process, stating that the drug was removed because "benefits of rosiglitazone no longer outweigh the risks."
Doctors do not respond adequately to FDA boxed warnings on drug labels, resulting in significant exposure of patients to potentially unsafe medications, according to researchers, who use the rosiglitazone saga as an example.
Dr Joshua Sharfstein, principal deputy commissioner of the FDA, discusses the recent FDA decision to allow Avandia to stay on the market with restricted access and compares the decision with the European approach that suspended the drug.
Diabetes doctors convened at the EASD meeting in Stockholm have given their verdict on the differing decisions made by the European and American regulatory authorities yesterday on the fate of rosiglitazone. In the US, Nissen says he is "pleased" by the EMA actions; the FDA moves are "reasonable," he added.
UPDATED // After months of deliberations, the FDA has opted to allow Avandia to stay on the market, but only with severe restrictions. It also opted to stop the TIDE trial, pending a rereview of the RECORD trial. In contrast, the EMA has ordered the suspension of all rosiglitazone-containing products.
Two employees of the FDA have raised questions about members of a previous advisory panel who had already voted to keep rosiglitazone on the market being invited to the recent review meeting to decide the future of the drug.
It has emerged this week that UK experts recommended the withdrawal of the diabetes drug rosiglitazone from the British market in July, although this recommendation was not made public at the time. However, because the drug was approved centrally by the European Medicines Agency, only it can revoke the license, says the UK regulatory body; the EMA is discussing rosiglitazone today, although no final decision is expected on the product until the end of this month.
The study isn't a substitute for a bona fide prospective randomized trial, but it is large and controlled for a lot of potential confounders. Why its conclusions contrast with those of some prior studies isn't known for sure, but there's at least one good possible reason.
Following the recent controversial FDA advisory panel decision on rosiglitazone, the drug's future availability is uncertain. But how much does that matter to the treatment of most patients with typeá2 diabetes?
Dr David Capuzzi earned $14á750 as a member of the company's speakers' bureau but received the money related to talks about Lovaza and not for rosiglitazone. DráAbraham Thomas received a few thousand dollars for speaking on behalf of pioglitazone, Avandia's rival.
UPDATED // Near the end of two days of exhaustive, often-polarized debate, 12 panel members said the drug should be withdrawn, with no other choice getting as many votes. But the other 20 votes were spread across three out of four other options, all suggesting that the drug could stay on the market, with certain provisions.
UPDATED // A marathon of 11 hours of presentations has likely left the joint Endocrinologic and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees reeling in confusion. Day two promises more time for questions and reflection before the all-important vote.
If GlaxoSmithKline thought today was its last chance to take a breath before the onslaught of the two-day safety hearing on its diabetes drug Avandia by a joint FDA advisory committee, starting tomorrow, it was mistaken. In the latest twist to this long-running saga, it emerged that the European Medicines Agency is also to review the drug's safety this summer.
UPDATED // The FDA documents, which provide a glimpse of what the agency's presentations will look like next week, are largely critical of rosiglitazone's safety record and of the ethics of the ongoing TIDE trial. In sharp contrast, GlaxoSmithKline's documents reiterate the need for a randomized controlled trial to resolve uncertainties and conclude that by and large the data support "the overall positive risk profile of rosiglitazone."
Investigators with the trial gave reporters at the ADA 2010 Scientific Sessions a cursory preview of a post hoc analysis to be reported in more detail later in the meeting: the controversial drug apparently wasn't associated with an excess risk of MI or other cardiovascular events in the BARI 2D trial. The finding, with all its limitations, adds to an already-contentious debate about the drug's safety.