Abbott is withdrawing its anti-obesity drug sibutramine from the European Union markets at the urging of the European Medicines Agency.

The EMEA announced Jan. 21 that it is recommending to the European Commission that the drug, marketed as Reductil , Reduxade Zelium and other trade names in the EU, be suspended due to a study showing that people taking sibutramine have an increased risk of cardiovascular events.

The same day, FDA announced that it was requesting that Abbott strengthen the Meridia labeling to contraindicate use of the drug in people with a history of cardiovascular disease, including heart attack, stroke, heart arrhythmias and uncontrolled hypertension. The label already includes warnings against the use of Meridia in patients with cardiovascular disease.

The actions come two months after FDA sent a letter to health professionals and patients advising them of preliminary results from Abbott's Sibutramine Cardiovascular Outcomes Trial (SCOUT). It found that patients receiving Meridia had an 11.4 percent rate of cardiovascular events compared to 10 percent of those receiving placebo.

FDA said additional data from SCOUT indicate the increased risk occurred only in patients with a history of cardiovascular disease. It said Abbott is expected to submit the full study report in March. After it reviews this and other relevant information the agency will convene an advisory committee to discuss Meridia's benefit/risk profile and determine if additional regulatory actions should be taken.

Abbott said more than 90 percent of patients in SCOUT had underlying cardiovascular disease and most were not eligible to receive the drug under current labeling and prescribing information.

For obesity drug developers, the study results mean that it would be reasonable to expect that FDA will now consider requiring an outcomes trial before approval of any new product (¹ Also see "Will A CV Warning On Meridia Alter FDA Views On Obesity Drugs?" - Pink Sheet, 30 November, 2009.). But the decisions to opt for label change and not a risk management plan suggest that the risks seen in the trial were not all that profound.

EMEA's Committee for Medicinal Products for Human Use acknowledged that sibutramine was not recommended for most of the patients enrolled in the study and that the duration of the study was longer than normally recommended. But it concluded that the risks of sibutramine-containing medicines are greater than their benefits.

"Because obese and overweight patients are likely to have a higher risk of cardiovascular events, the committee was of the opinion that the data from SCOUT are relevant for use of the medicine in clinical practice," EMEA stated. The committee also said data shows that weight loss from sibutramine is modest and may not be maintained after discontinuing the drug. EMEA forwarded its recommendation to suspend marketing to the European Commission.

"We believe there are many patients who benefit from sibutramine and respectfully disagree with the committee's opinion and the recommendation to suspend the medicine," an Abbott spokesperson stated. "However, we will act promptly to comply with the committee's recommendation."

Abbott does not break out Meridia sales by country. In 2009, the drug had global sales of approximately $300 million, the majority from outside the U.S.

Sidney Wolfe, the head of Public Citizen, strongly objected to FDA's request to bolster the labeling rather than withdraw the drug. "Once again, it is clear that under its present leadership, FDA's CDER [Center for Drug Evaluation and Research] is not willing to adequately protect the public health even with clear evidence of risks outweighing benefits for drugs such as Meridia," he said.

Wolfe said there has never before been a long-term outcome study on weight reduction drugs and the implications of SCOUT go beyond Meridia.

Public Citizen submitted a second petition to FDA calling for a ban on Meridia after FDA reported preliminary study results (² Also see "Public Citizen Re-Petitions FDA To Withdraw Obesity Drug Meridia" - Pink Sheet, 7 December, 2009.). The consumer watchdog group first asked FDA to remove Meridia from the market in 2002 based on pre-approval clinical trials that showed obese patients receiving the drug had increased blood pressure, pulse rate and palpitations. FDA responded to that petition in 2005 saying the SCOUT study would provide an objective assessment of Meridia's safety profile. The EMEA requested that Abbott conduct the study as a post-marketing commitment to evaluate cardiovascular safety in a high-risk patient population.

- Brenda Sandburg ( ³ b.sandburg@elsevier.com )

Weighing Obesity Risk: FDA, EMEA Use Different Scales For Abbott's Meridia

More from Archive

More from Pink Sheet