>>TARRYTOWN, N.Y.--(BW HealthWire)--Sept. 11, 2001--Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN - news) released additional follow-up data from its Phase II study of AXOKINE® for the treatment of obesity.
The Company reported that, on average, patients treated with AXOKINE for 12 weeks maintained weight loss, compared with baseline weight, for at least 36 weeks following cessation of treatment. In contrast, patients receiving placebo not only failed, on average, to lose weight during the treatment phase, but gained weight in the 36 weeks following cessation of placebo. The initial 12-week treatment phase was conducted in a double-blind and placebo-controlled manner, and the study remained blinded and placebo-controlled during the follow-up period. The 36-week follow-up results reported today extend similar findings at 12 and 24 weeks of follow-up as reported by the Company earlier this year. AXOKINE was generally well tolerated during the trial and was not associated with any reported serious adverse events, either during the trial or the subsequent follow-up period.
``We've reached an important milestone in our obesity studies. On average, patients treated with AXOKINE have experienced medically meaningful weight loss and have been able to sustain weight reduction for nearly a year,'' noted Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. ``With obesity increasingly recognized as a causative or contributing factor in serious diseases such as diabetes, hypertension, and coronary artery disease, we can no longer afford to treat this problem simply as a life-style issue. The International Obesity Task Force (IOTF) estimates that more than 1 billion people worldwide are affected by weight problems, and that the related healthcare costs are mounting. While additional work and clinical testing still need to be carried out in the Phase III program we recently initiated, we believe that AXOKINE has the potential to be an important therapy for patients suffering from this major health problem.''
As previously reported, during the treatment phase of Regeneron's Phase II clinical trial of AXOKINE, severely obese patients demonstrated medically meaningful and statistically significant weight loss in a dose-dependent manner compared with placebo. In this trial, patients who received the optimal 1.0 mcg/kg dose of AXOKINE averaged approximately 10 pounds more weight loss than patients on placebo over the 12-week treatment period. Regeneron now reports follow-up analysis in which patients who underwent 12 weeks of treatment were followed for 36 weeks after treatment cessation. At the end of this follow-up period, patients treated with the optimal 1.0 mcg/kg dose of AXOKINE averaged a 12.4 pound weight loss compared with their baseline weight, while placebo treated patients gained 3.1 pounds compared with their baseline weight, for a total differential compared with placebo of 15.5 pounds. Combining all the AXOKINE-treated dose groups, patients averaged a 6.7 pound weight loss compared with baseline weight, for a total differential compared with placebo of 9.8 pounds. The results are based on preliminary analysis of the most recent interim data.
Results for patients who received AXOKINE or placebo during the 12-week treatment period and the subsequent follow-up periods are summarized below:
Mean Change from Baseline Weight (Pounds)
All Available Data for All Patients
AXOKINE
Placebo 0.3 mcg/kg 1.0 mcg/kg 2.0 mcg/kg Combined
AXOKINE
12 Weeks + 0.2 -3.5 -9.1 -8.0 -6.9
(end of
blinded
treatment) (n=23) (n=23) (n=26) (n=19) (n=68)
18 Weeks + 2.2 -4.7 -9.6 -7.8 -7.4
(6 weeks off
treatment) (n=19) (n=22) (n=25) (n=18) (n=65)
24 weeks + 1.9 -4.8 -9.9 -5.8 -7.1
(12 weeks off
treatment) (n=19) (n=18) (n=23) (n=17) (n=58)
36 weeks + 3.8 -4.4 -12.4 -5.4 -7.8
(24 weeks off
treatment) (n=16) (n=18) (n=19) (n=12) (n=49)
48 weeks + 3.1 -2.9 -12.4 -3.9 -6.7
(36 weeks off
treatment) (n=16) (n=17) (n=17) (n=11) (n=45)
Results for just those patients who completed the full 48 weeks in
the study are:
Mean Change from Baseline Weight (Pounds)
Data for Patients Who Completed 48 Weeks of Follow-up
AXOKINE Combined
Placebo 0.3 mcg/kg 1.0 mcg/kg 2.0 mcg/kg AXOKINE
n=16 n=17 n=17 n=11 n=45
12 Weeks + 1.1 -5.0 -10.4 -8.0 -7.8
(end of
blinded
treatment)
18 Weeks + 3.5 -5.4 -12.0 -9.7 -8.8
(6 weeks off
treatment)
24 weeks + 2.7 -5.0 -13.1 -7.7 -8.8
(12 weeks off
treatment)
36 weeks +3.8 -4.7 -15.6 -5.4 -8.8
(24 weeks off
treatment)
48 weeks +3.1 -2.9 -12.4 -3.9 -6.7
(36 weeks off
treatment)
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 of the AXOKINE receptor and the 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 a paper published in the April 10, 2001 issue of the Proceedings of the National Academy of Sciences (PNAS), Regeneron reported that obese animals ate less and lost weight when treated with AXOKINE. Moreover, following cessation of treatment, the animals did not exhibit the binge overeating and immediate rebound weight gain that is characteristic of dieting.
Phase II Clinical Trial
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 with those receiving placebo in a dose-dependent manner.
In the trial, 170 severely or morbidly obese patients were randomized into 5 groups who received 12 weeks of daily treatment administered under the skin by patient self-injection. Of these groups, 4 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 with placebo.
A fifth group consisted of patients who received a daily dose of 1.0 mcg/kg for 8 weeks, followed by a blinded withdrawal period in which they received placebo for 4 weeks. Patients in this group lost weight during the treatment period and, on average, did not appear to regain weight either during the 4 weeks that they received placebo or, based on preliminary data, in the subsequent 36-week follow-up period after the end of the trial.
Phase III Clinical Program
In July 2001, Regeneron initiated a Phase III clinical program of AXOKINE for the treatment of obesity. The program will assess the safety and efficacy of AXOKINE for weight loss in overweight and obese patients. The initial pivotal trial has begun to enroll approximately 2,000 patients at over 60 study sites across the United States in a double-blind, randomized, placebo-controlled study. This initial trial will have a 12-month treatment period, in which patients will receive daily subcutaneous self-injections of placebo or AXOKINE at a dose of 1.0 microgram (mcg) per kilogram (kg) of body weight. The treatment period will be followed by a 12-month open-label safety extension phase, during which all patients will receive AXOKINE. Endpoints of the study are based on changes in body weight versus baseline during the treatment period.<<
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