Feb. 28, 2001--At the ``Keystone Symposium on Obesity and the Regulation of Energy Homeostasis'' in Taos, New Mexico, George D. Yancopoulos, M.D., Ph.D., President of Regeneron Research Laboratories and Chief Scientific Officer of Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN - news) reported that patients who received AXOKINE® therapy in the Company's recently completed Phase II clinical trial maintained their average weight loss relative to patients who received placebo three months following their last treatment with AXOKINE. In addition, patients who were treated with AXOKINE for only eight weeks pursuant to the study protocol continued to maintain their average weight loss for an additional four months following their last treatment. Dr. Yancopoulos explained that this information is based on a preliminary analysis of interim data as the Company continues to monitor patients for a one year period following the end of the Phase II trial.
Results for the patients who received AXOKINE or placebo for twelve weeks and have completed the full twelve week follow-up are summarized below:
Mean Change from Baseline Weight
(Pounds)
Placebo 0.3 mcg/kg 1.0 2.0 mcg/kg
(n=15) (n=16) mcg/kg (n=17)
(n=19)
12 Weeks + 1.7 - 4.6 - 9.7 - 7.6
(end of blinded
treatment)
18 Weeks + 2.9 - 4.9 - 11.0 - 7.6
(6 weeks off
treatment)
24 weeks + 3.8 - 4.2 - 10.8 - 5.5
(12 weeks off
treatment)
Dr. Yancopoulos reviewed results from Regeneron's Phase II clinical trial of AXOKINE, originally described in November 2000, in which severely obese patients demonstrated medically meaningful and statistically significant weight loss in a dose-dependent manner compared to placebo. In this trial, patients who received the optimal dose of AXOKINE averaged approximately 10 pounds more weight loss than patients on placebo over the twelve week treatment period.
Dr. Yancopoulos noted that maintenance of weight loss in severely obese patients for a period of time following cessation of AXOKINE treatment was consistent with animal studies conducted by Regeneron scientists. In these animal studies, AXOKINE induced weight loss without triggering the hunger signals or associated stress responses that are otherwise associated with dieting and food deprivation. These findings may explain why cessation of AXOKINE treatment in animals does not result in binge overeating and immediate rebound weight gain seen upon allowing animals to eat after restricting food intake (forced dieting). These preclinical findings will be described in detail in a paper to be published shortly in the Proceedings of the National Academy of Sciences (PNAS).
Subject to discussions with regulatory authorities, Regeneron plans to initiate Phase III testing of AXOKINE in mid-2001 to gather information about the safety and efficacy of the drug in larger numbers of patients over longer periods of time.
Background
In November 2000, Regeneron reported the preliminary results of a randomized, double-blind, placebo-controlled Phase II dose-ranging trial to study the safety and efficacy of AXOKINE in severely obese patients. In the trial, patients treated with AXOKINE showed medically meaningful and statistically significant weight loss compared to those receiving placebo in a dose-dependent manner. The drug was generally well tolerated and was not associated with any reported serious adverse events. The most common reported side effect was injection site reactions (skin redness), which occurred in all patient groups, including placebo, and were generally mild. Other side effects associated with the drug included cough and vomiting, which were notable only in the highest dose group, and nausea, which occurred most frequently in the highest dose group.
In the trial, 170 severely or morbidly obese patients were randomized into five groups who received twelve weeks of daily treatment administered under the skin by patient self-injection. Four of the groups were part of the pre-specified primary analyses and consisted of groups receiving placebo, a daily dose of 0.3, 1.0 or 2.0 micrograms (mcg) of AXOKINE per kilogram (kg) of body weight. All AXOKINE-treated groups showed statistically significant weight loss compared to placebo.
A fifth group consisted of patients who received a daily dose of 1.0 mcg/kg for eight weeks, followed by a blinded withdrawal period in which they received placebo for four weeks. Patients in this group lost weight during the treatment period and did not appear to regain weight while taking placebo. Moreover, these patients maintained average weight loss for the additional three months that were the subject of the preliminary analysis reported on by the Company today.
AXOKINE: Scientific Rationale in Obesity
AXOKINE is a genetically re-engineered version of a naturally occurring human protein known as ciliary neurotrophic factor (CNTF). Preclinical studies have shown that injected AXOKINE travels through the bloodstream to reach a critical area of the brain, known as the hypothalamus, that regulates body weight. AxokinE is believed to bind to specific receptors and activate key signaling pathways in the hypothalamus that suppress appetite and reduce body weight. Both the site and mechanism of action of AXOKINE are similar to those of leptin, a natural hormone regulator of body weight that is released by fat cells. However, in animal models of the most common form of obesity (diet-induced obesity), animals are resistant to administration of leptin, while AXOKINE is able to cause substantial weight loss.
In animal studies, AXOKINE caused weight loss and produced selective loss of fat (as opposed to lean body mass). In addition, unlike the reaction to restricting food intake, cessation of AXOKINE treatment did not lead to an immediate rebound in weight.... |
