Experimental Weight-Loss Pill Passes Early Test
FRIDAY Dec. 12, 2008 -- Researchers are hoping that an experimental new weight-loss drug will prove to be a valuable new weapon in the crusade against obesity.
In recently released phase 2 trials, the drug, known as lorcaserin, resulted in substantial weight loss in obese men and women.
"Lorcaserin is a completely novel mechanism and we think it can bring very robust weight loss. But, also, the safety profile of the compound is excellent," said Dominic P. Behan, co-founder and chief scientific officer of Arena Pharmaceuticals in San Diego, which makes the drug and sponsored a study published in the Dec. 4 issue of the journal Obesity.
"We demonstrated a highly statistically significant, progressive weight loss. This study involved no diet or exercise and the weight loss was rapid and we saw the weight loss in as little as two weeks," he added.
A phase 3 trial is under way and, if all goes well, Arena Pharmaceuticals may file a new drug application with the U.S. Food and Drug Administration at the end of 2009, Behan said.
With some two-thirds of Americans either overweight or obese, the need for an effective weight loss tool is tremendous. Excess weight can lead to a variety of health problems, including heart disease, stroke, cancer, arthritis and type 2 diabetes.
"Obesity is an epidemic," said Dr. Stuart Weiss, a clinical assistant professor of medicine at New York University's Langone Medical Center in New York City. "Diabetes trails behind obesity by a short few years and the numbers of patients that are developing diabetes is staggering."
Diet and exercise are proven antidotes for excess weight, but few people are able to sustain such changes and, even if they lose weight, will regain it.
Some weight-loss drugs are already on the market -- such as Xenical and Meridia -- but have certain side effects.
The drug Fen-phen, a combination of fenfluramine and dexfenfluramine, worked for many but was withdrawn from the market in 1997 when it was linked with increased rates of heart valve problems in patients.
Fen-phen acted on serotonin receptors both in the brain and in the heart and therein lay the problem, Behan said.
"The challenge was to design a compound that was purely selective for the receptor involved, namely the 2c receptor [located in the hypothalamus region of the brain and involved in weight loss] and avoiding the 2b receptor [located in the heart]," Behan said.
The result was lorcaserin, which targets the 5-HT2C serotonin receptor only.
For the phase 2 trial, 469 men and women with a body mass index ranging from 30 to 45 were randomly assigned to one of four groups: 10 milligrams (mg) of lorcaserin once a day, 15 mg once a day, 10 mg twice a day, or a placebo.
Participants taking lorcaserin at 10 mg, 15 mg and 20 mg a day lost 4 pounds, 5.7 pounds and 7.9 pounds, respectively, over the 12-week period. Those in the placebo group lost less than a pound.
In the 10 mg, 15 mg and 20 mg groups, respectively, 12.8 percent, 19.5 percent and 31.2 percent of participants lost 5 percent or more of their starting body weight, versus only 2.3 percent of patients on the placebo.
Participants taking the two higher doses of lorcaserin also shaved inches off their waist and dropped their cholesterol levels.
Also, their echocardiograms -- ultrasound images of the heart -- were normal.
"It [lorcaserin] certainly looks a bit better [than other weight-loss medications]," Weiss said. "We don't have much out there. They're really just modest medications and they don't do much at all."
Visit the U.S. Centers for Disease Control and Prevention for more on overweight and obesity.
Posted: December 2008