GlaxoSmithKline is breathing a huge sigh of relief this morning following a recommendation from a US Food and Drug Administration advisory panel that the drug giant’s controversial diabetes treatment Avandia should remain on the market, albeit with new safety warnings.
The company’s shares had been on the slide ahead of the meeting and indeed since May when a meta-analysis published in May in the New England Journal of Medicine claimed that users of Avandia (rosiglitazone) increased cardiovascular risks. However, the joint meeting of the FDA Endocrinologic and Metabolic Drugs and the Drug Safety and Risk Management Advisory Committees ended with a 22 to 1 vote in favour of keeping the drug on the market in the USA.
GSK welcomed the “nearly unanimous recommendation” of the advisory committee and chief medical officer Ronald Krall claimed that it had recognised “the debilitating nature of this disease and the importance of multiple treatment options”. He noted that this was the “first opportunity for these scientific experts to review the full data behind Avandia” and the company believes the correct decision has been made.
However the FDA committee did vote 20-3 that there was sufficient evidence of increased heart disease risk associated with Avandia, The panel said that certain groups should not take the drug, including people taking nitrates or insulin, and that a ‘black box’ warning needs to be added to the label. It was also recommended that further studies be carried out.
Other speakers at the meeting still maintain that the steps proposed by the committee do not go far enough and most vocal of those was David Graham. Dr Graham, the FDA drug safety officer who caused a stir in 2004 by criticising the agency’s handling of Merck & Co’s withdrawn painkiller Vioxx (rofecoxib), called for the withdrawal of Avandia, saying that waiting for yet more data could subject as many as 2,200 people a month to serious side effects from the drug. He added that “any drug that increases the risk of heart disease makes no sense".
Gerald Dal Pan, director of the agency's office of surveillance and epidemiology, agreed with his colleague and both he and Dr Graham, in their analysis of the risks of Avandia, presented data on a head-to-head comparison of the drug with another thiazolidinedione Actos (pioglitazone), manufactured by Takeda and co-marketed with Eli Lilly. However the panel members said that the data had not yet been peer reviewed and had not been presented to them in time for a full evaluation.
Furthermore, once Drs Graham and Dal Pan had spoken, Robert Meyer, director of the FDA's office of new drug evaluation, immediately disagreed and stated that “I think it’s important that the committee understand there’s a fundamental disagreement” within the agency. Rebecca Killion, a patient representative on the advisory panel, said that withdrawal was not the best option as “we are being asked to take a very draconian action based on studies that are very inadequate for us to make that kind of decision”.
As for Steven Nissen, whose article in the NEJM started the furore, he said he was “very satisfied” the committee voted to put a strong warning on the drug, but others are less likely to be placated. Sidney Wolfe, director of the Health Research Group at the influential pressure group Public Citizen, told the panellists about pre- and post-approval evidence of cardiac toxicity, liver toxicity and anaemia associated with the drug and discussed post-approval evidence of increased bone fractures in women and damage to patients’ vision.
“There is no evidence of any uniquely beneficial clinical outcome for Avandia and growing evidence of unique risks in multiple organ systems,” said Dr Wolfe. “If Avandia were up for approval today, based on what is now known, it would be summarily rejected. There should not be a double standard for removing it from the market.”
Nevertheless, the fact remains that GSK has won the day for the timebeing and at 10am the firm’s shares had climbed 3.3% to 1,225 pence. However, the whole Avandia issue is far from settled and the panel’s chair, Clifford Rosen, noted that “we have provided at least some guidance for where the risk is [but] this is not the end of the road." By Kevin Grogan