Two weeks ago I wrote about GlaxoSmithKline’s Avandia (rosiglitazone) being under the magnifying lens of regulators because of cardiovascular safety concerns and the verdict is now in: the treatment is being pulled completely from the EU market and will face severe restrictions in the US.
Controversy has surrounded Avandia ever since it was first approved but in recent months there has been increasing pressure — including published articles and a UK television documentary highlighting the risks associated with Avandia — on the FDA and the European Medicines Agency (EMA) to take action.
“The availability of recent studies has added to the knowledge about rosiglitazone and overall, the accumulated data support an increased cardiovascular risk of rosiglitazone,” said a statement from the EMA. “In view of the restrictions already in place on the use of rosiglitazone, the Committee could not identify additional measures that would reduce the cardiovascular risk.”
As such, the EMA concluded that the benefits of the medicine no longer outweigh the risks in any groups of patients and recommended marketing authorization suspension, which has been forwarded to the EC for the adoption of a legally binding decision.
The move was strongly backed by the UK’s Medicines and Healthcare products Regulatory Agency, which conducted its own assessment of the safety of rosiglitazone and concluded that the product no longer had a place on the UK market. In the UK, the Diabetes UK charity has also supported the news, but added in a statement: “We would urge the EMA to make swifter decisions in the future to ensure patient safety.”
The marketing authorization suspension will remain in place unless GSK can provide “convincing” data to identify a group of patients in whom the benefits of the medicines outweigh their risks.
On the other side of the Atlantic, the FDA has chosen not to withdraw the product completely but has implemented stringent restrictions until “more substantial evidence of its safety becomes available”, according to a statement from Janet Woodcock, MD of the FDA’s Center for Drug Evaluation and Research. She also added that the “cardiovascular safety profile of rosiglitazone is still an open question because there are conflicting data on the existence and magnitude of the risk”.
The FDA has also ordered GSK to undertake a restricted access program to assure safe use and commission an independent re-adjudication of the RECORD study — a clinical trial initiated in 2001 that examined Avandia’s cardiovascular safety, but which has sparked a great deal of controversy regarding the validity of the data. The FDA has also placed GSK’s TIDE study, designed to compare the cardiovascular safety of Avandia and Actos, on hold and rescinded all regulatory deadlines.
GSK has said it will be working hard to clear the name of its product. “The company continues to believe that Avandia is an important treatment for patients with type 2 diabetes and is now working closely with the FDA and EMA to implement the required actions,” said a statement.
The loss of sales from the once blockbuster-touted product will be a heavy loss to GSK. According to analyst firm Datamonitor, a number of patients will probably switch to Takeda’s competitor product Actos; however, this product is also currently being subjected to a safety review following a possible link with bladder cancer. “The chances for Takeda to capitalize on Avandia’s further misfortune are limited, as Actos loses patent protection in January 2011,” explained Christine Henry, Healthcare Analyst at Datamonitor, in a statement.
More bad luck for GSK
Bad luck often comes in threes and this also seems to be true for GSK — two of the company’s other medicines, Rotarix and Pandemrix, have also been in the headlines this week for the wrong reasons.
Rotarix, a vaccine for infants to prevent rotavirus disease, has faced a labeling change because of research suggesting that it may increase the risk of intussusception — a potentially fatal bowel problem. Considering a similar vaccine from Wyeth was pulled off the market in 1999 for the same reason, it’s not a good omen for GSK.
The third bit of bad luck stems from Pandemrix. Earlier this month, the safety of the pandemic influenza vaccine was being investigated by the EMA following a possible link between vaccination and narcolepsy. On the plus side, the latest update from the EMA does not confirm a link between Pandemrix and narcolepsy, but the investigation is still ongoing, and it will be 3–6 months before GSK finds out whether or not the vaccine is in the clear.