The results of the two-year trial, released at the American Heart Assn.'s Scientific Sessions in New Orleans on Nov. 9, "raised no red flags," said lead investigator Dr. F. Xavier Pi-Sunyer of St. Luke's/Roosevelt Hospital Center in New York. That virtually assures that Acomplia, made by Paris-based Sanofi-Synthelabo, will proceed on schedule to file for approval from the Food & Drug Administration in 2005.
Sanofi and Pi-Sunyer, though, would prefer that Acomplia be described as a cardiovascular drug and not a diet drug. That's because it appears to do far more than promote weight loss. Acomplia also reduces cardiovascular risk factors such as high cholesterol and can be used to stop nicotine addiction.
SCRAMBLED SUBJECTS. The drug is the first of a new class of compounds under development to block receptors found in both the brain and in fat tissue called cannabinoid type 1 (CB1). These receptors go into overdrive when exposed to excessive food intake or chronic tobacco use, and blocking them dampens those urges.
The study is especially significant because for obese patients to maintain weight loss over an extended period is extremely difficult. In the results reported at the AHA meeting, 3,040 patients, 80.7% of them women, were divided into three groups -- those receiving 20 milligrams of Acomplia (considered the ideal dose), those receiving 5 mg, and a placebo. They were all placed on a mild diet. After one year, the patient sample was scrambled again, so that many of those on Acomplia were switched without their knowledge to placebo.
At the two-year mark, 62.5% of patients on the 20-mg dose lost more than 5% of their initial body weight vs. 33.2% of those on placebo. Over the same period, 32.8% of patients on 20 mg lost more than 10% of their initial body weight, vs. 16.4% on placebo.
WIDE-RANGING GOOD. Those patients who switched from Acomplia to placebo after one year didn't sustain their weight loss. Concerns have often arisen that because Acomplia blocks a receptor involved in pleasure, might cause depression, but Pi-Sunyer said no differences appeared among the three groups as measured by the standard Hospital Anxiety Depression Scale.
Acomplia produced other benefits, however. Waist circumference in the 20-mg group was reduced by an average of 3.1 inches, vs. 1.5 inches in the placebo group. Pi-Sunyer noted that the drug's effect on HDL-cholesterol, triglycerides, and insulin levels appeared to be twice what would normally be expected from the degree of weight loss achieved, indicating that Acomplia can improve heart health independent of any weight loss.
It also reduced by one-third the number of patients diagnosed with metabolic syndrome, a set of serious health conditions that dramatically increases a person's chance of developing heart disease or diabetes. "This drug is really a double whammy for patients," Pi-Sunyer said, because it addresses both cardiovascular risk factors and weight gain.
Pi-Sunyer's study is the most comprehensive of all the Acomplia tests presented to date. In all, late-stage clinical trials have been conducted with 6,600 overweight or obese patients, while other smoking-cessation trials are ongoing. With the two-year data now in, Acomplia is on track for FDA approval, and the 30% of Americans who are overweight could have a new drug for their condition by 2006. Arnst is a senior writer for BusinessWeek