April 10, 2001--Scientists at Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN - news) report in a paper in the April 10, 2001 issue of the Proceedings of the National Academy of Sciences (PNAS) that obese animals ate less and lost weight when treated with AXOKINE®, Regeneron's clinical candidate for the treatment of obesity. Moreover, following cessation of treatment, the animals did not exhibit the binge overeating and rebound weight gain that is characteristic of forced dieting, apparently because AXOKINE reduced the increased hunger signals normally associated with weight loss.
These findings parallel the results of a Phase II clinical trial of AXOKINE that Regeneron completed in late 2000. In that trial, severely obese patients treated with AXOKINE showed medically meaningful and statistically significant weight loss compared to those receiving a placebo. Patients who received the optimal dose of drug over the twelve-week treatment period averaged ten pounds more weight loss than patients on placebo. Preliminary analysis of available data for patients in this dose group who were followed for another twelve weeks after their final AXOKINE treatment shows that they maintained their average weight loss during this post-treatment follow-up period.
In the study published in PNAS, mice were fed a high fat diet until they were 30% overweight. Half the animals were then treated for three or seven days with AXOKINE, which caused them to reduce their food intake. The remaining mice were placed on a forced diet, on which their food intake was restricted to the amounts eaten by the treated animals. Over the treatment period, both groups of mice consumed the same amounts of food and lost similar amounts of weight. In both groups, weight loss was almost exclusively related to loss of fat, as opposed to lean body mass.
When the treatment period ended, all animals were allowed free access to food. The animals on the forced diet immediately resorted to binge overeating, and their weight rapidly returned to pre-restriction levels. At that point, their food intake normalized, suggesting that these animals had retained a ``memory'' of the calories lost during the food restriction period and made up for these missed calories when allowed free access to food. In contrast, the animals treated with AXOKINE did not overeat following cessation of treatment and did not have an immediate rebound in weight.
Philip D. Lambert, Ph.D., Staff Scientist at Regeneron and principal author of the study, commented, ``In animal models, AXOKINE appears to be able to reduce food intake without triggering hunger signals in the brain or associated stress responses. We believe that AXOKINE may alter, at least for some amount of time, the body weight settings in the brain, so the lower weight seems natural. Therefore, even when drug treatment is ended, the animal does not feel starved and does not respond by overeating.''
George D. Yancopoulos, M.D., Ph.D., President of Regeneron Research Laboratories and Chief Scientific Officer of Regeneron, added, ``One of the most satisfying aspects of our studies with AXOKINE is the remarkable correspondence between the effects observed in human patients and the animal studies. Rarely do preclinical findings so nicely predict the results of Phase I and Phase II clinical trials, reinforcing our belief that AXOKINE may prove to be a useful drug for treating obese human patients.'' ... |
