NYT19980614.0047 NEWS NEWSWIRE A potential anti-obesity drug being developed by Amgen Inc., which made headlines a few years ago by sharply reducing body fat in mice, has now been found to contribute to weight loss in people as well, scientists reported Sunday. The results, the first clinical trial data presented at a scientific meeting, could help lay to rest recent speculation that the drug, leptin, would not work in humans. The results, however, also seem to suggest that leptin will not be a sure-fire cure for obesity. ``At appropriate doses it causes weight loss in some people,'' said Dr. Andrew S. Greenberg, who directs obesity research at Tufts University and at the New England Medical Center in Boston. He was the lead author of the study presented Sunday at the annual scientific sessions of the American Diabetes Association in Chicago. In the Phase I trial, mainly intended to test leptin's safety, obese people who dieted and got the highest dose of leptin lost an average of 15.6 pounds after six months, an 8 percent weight reduction. Those who dieted but received a placebo lost an average of only 3.7 pounds, a reduction of about 1.5 percent to 2 percent, Greenberg said. But leptin did not work for everyone. Of the eight people who got the highest dose, one had no weight loss and a second actually gained weight. The variability is to be expected because obesity has many causes, Greenberg said. He said the results were significant in two respects. One is that weight loss increased as dosage increased, a sign the drug is effective. Second, it removes the doubts as to whether leptin would work at all. Leptin is produced by fat cells in the body and helps keep weight in check, apparently by signaling the brain to suppress the appetite or to burn off fat more quickly. The discovery of leptin and the gene to produce it three years ago created a stir because it seemed to point to a genetic basis for obesity and a potential new therapy. Mice that lacked the gene to produce leptin were obese. Moreover, both obese and normal mice quickly lost body fat when given injections of leptin made by genetic engineering. Amgen licensed the patents from Rockefeller University in New York, where the initial discovery was made. But hopes that leptin would be an anti-fat potion dimmed when subsequent research showed that obese people actually had higher levels of leptin than others, suggesting that the problem is not a lack of leptin but an inability to use it. If that were the case, then giving even more leptin might be futile. But the study presented Sunday suggested that extra leptin can help, as if giving more of it helps compensate for the inefficiency in using it. Still, Dr. Xavier Pi-Sunyer, professor of medicine at Columbia University, said the weight loss reported for leptin appears only equivalent to that of existing weight-loss medications like Meridia by the Knoll Pharmaceuticals unit of BASF. Also, the existing medications are pills while leptin must be injected daily. Some patients taking the highest dose of leptin needed three shots a day and developed skin irritations from the injections. ``I think you really have to show a better response with injectables because you have to compete head to head with the orals,'' Dr. Pi-Sunyer said. ``Leptin in my mind is a little bit of a disappointment.'' But Amgen hopes that as a natural protein, leptin will have fewer side effects than weight-loss pills, some of which have been withdrawn from the market. Amgen, which is based in Thousand Oaks, Calif., has started a Phase I trial with a second-generation leptin that it hopes will allow for greater doses with fewer shots. It is continuing with Phase II trials of the first-generation leptin to treat obesity and to control blood sugar levels in overweight diabetics. Amgen is under Wall Street pressure to come up with a new hit, after going several years without a significant new drug.