Abbott Laboratories has voluntarily withdrawn Meridia from the US market, just a month after a regulatory panel could not decide whether the obesity drug should be pulled.
The company says it is taking this action at the request of the US Food and Drug Administration. The agency made the request based primarily on results from the 10,000 patient, six-year SCOUT study, which was suggested by the European Medicines Agency as a post-marketing commitment to evaluate cardiovascular safety in high-risk patients taking Meridia (sibutramine).
Preliminary results of SCOUT came in at the end of last year and the EMA suspended Meridia, sold in Europe as Reductil, Reduxade and Zelium, in January after data revealed a 16% increase in the risk of serious heart events in a group of patients given sibutramine compared to placebo. There was also only a small difference in weight loss.
The SCOUT data led to a stricter label for Meridia in the USA and in September this year, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee was split (8-8) when it voted as to whether the drug should be withdrawn. A month later, however, the agency has had enough.
John Jenkins, director of the Office of New Drugs (OND) in the FDA’s Center for Drug Evaluation and Research, said that "Meridia’s continued availability is not justified when you compare the very modest weight loss that people achieve on this drug to their risk of heart attack or stroke".
Abbott - Meridia still has positive risk/benefit profile
However, while complying with the FDA's request, Abbott still believes "sibutramine has a positive risk/benefit profile in the approved patient population". The company notes that the majority of patients in SCOUT trial had underlying cardiovascular disease and were not eligible to receive Meridia under the current labelling.
Abbott adds that the SCOUT results "are in contrast to the vast body of sibutramine data for the on-label patient population, including 46 controlled clinical trials and more than six million patient years of use accumulated over 13 years". The company also claims that the FDA panel's recent split vote "highlights the complexity of the scientific debate and the different interpretations of the data, even by independent experts".
Gerald Dal Pan, director of the Office of Surveillance and Epidemiology (OSE) in the CDER, acknowledged that the patients in SCOUT "did not have the same characteristics as the patients for the approved indication in the USA" but "these results, combined with other available safety data raised serious questions about Meridia’s safety for all patient groups". The drug is also being withdrawn in Australia and Canada.
Withdrawal taken too long?
The Meridia saga has renewed the debate as to whether regulators have been acting quickly enough in removing suspect drugs from the market. Sidney Wolfe, who heads the Health Research Group at the influential US consumer group Public Citizen, said the FDA’s decision to ask Abbott to withdraw the drug is "commendable, but dangerously too late for all of the victims of its unacceptable risks".
The FDA approved Meridia in 1997 "despite pre-approval randomised trial evidence of significantly increased blood pressure and heart rate (both risk factors for heart attacks)", Dr Wolfe argues, "and despite the opposition of the FDA medical officer who reviewed the drug and the FDA’s advisory committee". Public Citizen petitioned to get Meridia banned in 2002 and since then, more than three million prescriptions have been filled for the drug, "with many patients inevitably having had heart attacks or strokes because of its known toxicity", he added.
Dr Wolfe says "it appears that [Meridia] was banned only because of the rare concordance" about pulling a drug between the FDA’s OND and the OSE, as documented in a memo sent last week from the two divisions to CDER director Janet Woodcock. He claims that in both of the other cases in which drugs have recently been taken off the market in Europe - the painkiller Darvon (propoxyphene) and GlaxoSmithKline's diabetes drug Avandia (rosiglitazone) - the OSE "also urged a ban in this country but was 'overruled' because of the reckless unwillingness of OND or Dr Woodcock to ban the drugs".
Dr Wolfe concluded by saying that both of the latter "unacceptably dangerous drugs remain on the market" in the USA, "predictably injuring or killing many people, who, unlike their European counterparts, do not have the government protecting them from drugs with no unique benefits, but significant, unique risks".