FDA advisory committee undecided on withdrawal of sibutramine from market
The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee did not reach an agreement today on whether or not to withdraw sibutramine hydrochloride capsules from the market.
The results were split: Eight members of the advisory panel voted to withdraw sibutramine (Meridia, Abbott Laboratories) from the market based on their perception of an increased risk for CV adverse events; six members recommended adding a boxed warning to the label and restricting distribution to trained physicians; two members recommended the boxed warning with increased monitoring of patient BP, heart rate, and body weight.
“The FDA criteria for efficacy is weight-loss,” John M. Flack, MD, MPH, FAHA, FACP, chair of the Department of Internal Medicine, Wayne State University School of Medicine, Detroit, said during the meeting. “CV risk reduction is good, but is not an FDA requirement. The absence of a real, proven benefit does not mean no benefit.” Flack voted against withdrawal of sibutramine.
The meeting cited results of the SCOUT trial, which indicated that 30% of patients assigned sibutramine had at least 5% weight-loss at 3 months compared with 19% of patients assigned placebo. Patients in the trial included those who were aged 55 years and older with a history of CV disease, type 2 diabetes or both.
Panel members who voted for more stringent monitoring argued removing sibutramine from the market would decrease an already sparse choice of weight-loss medications. Although a 5% weight-loss appears slight, the change is enough to improve obesity-associated conditions and increase self-esteem, according to patient advocate and member of the panel, Melanie Coffin.
However, as previously reported by Endocrine Today, participants who were assigned to sibutramine for a mean 3.4 years had an 11.4% risk for a primary outcome event (nonfatal MI, nonfatal stroke, resuscitation after cardiac arrest or cardiovascular death) compared with a 10% risk among patients assigned to placebo (HR=1.16; 95% CI, 1.03-1.31). The weight-loss drug was also linked to a 4.1% rate of nonfatal MI vs. 3.2% with placebo (HR=1.28; 95% CI, 1.04-1.57), and a 2.6% vs. 1.9% rate of nonfatal stroke (HR=1.36; 95% CI, 1.04-1.77).
Cheryl Renz, MD, of Abbott, suggested that SCOUT did not represent clinical practice, due to the inclusion of high-risk patients who were excluded in the current labeling. Renz presented strategies to mitigate the risk of CV adverse events, including training for physicians, patient education, and pretreatment screening for CV disease.
“Weight-loss is a symptomatic endpoint,” said committee member William R. Hiatt, MD, FACP, of the University of Colorado Denver School of Medicine, who voted for the withdrawal. In the case of sibutramine, “we see the benefit in weight-loss does not translate into clinical benefit, but instead it translates into clinical harm.”
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