Regeneron's Chief Scientific Officer Updates AXOKINE Obesity Data and Plans at American Society of Hypertension Annual Meeting
TARRYTOWN, N.Y.--(BUSINESS WIRE)--May 19, 2003--Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN - News):
Recently Completed Phase III Trial Suggests Early Weight Loss
Identifies Patients Likely to Benefit the Most from AXOKINE®
Treatment
Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN - News) today announced that George D. Yancopoulos, M.D., Ph.D., Executive Vice President, President of Regeneron Research Laboratories, and Chief Scientific Officer, presented an update of Phase III AXOKINE data and the development program for AXOKINE at the American Society of Hypertension (ASH) Annual Meeting in New York City. Dr. Yancopoulos presented on Saturday, May 17, at the ASH session entitled "New Frontiers in Pathophysiology and Therapy of Obesity," a session he also chaired. AXOKINE is a clinical candidate currently being evaluated by Regeneron for the potential treatment of obesity.
Initial results of the pivotal Phase III AXOKINE study, released on March 31, compared weight loss for trial participants treated with AXOKINE plus a weight control program that included diet and lifestyle modifications ("AXOKINE group") with weight loss for participants on a weight control program who received placebo ("placebo group"). The AXOKINE group achieved statistically significant benefits with regard to both primary endpoints of the study. A greater proportion of AXOKINE-treated patients lost at least 5% of their initial body weight compared with patients treated with a weight control program alone (25.1% vs. 17.6%, p(less than).001). Participants receiving AXOKINE also experienced a greater average weight loss than the weight control program population (6.2 lbs vs. 2.6 lbs, p(less than).001). Further, AXOKINE-treated patients showed improvements in obesity-associated co-morbidities.
Although the study met its primary endpoints and many individuals achieved a medically meaningful weight loss, the average weight loss was modest and limited by the development of antibodies, highlighting the need to target AXOKINE treatment to patients likely to benefit the most from this drug candidate.
At ASH, Dr. Yancopoulos reported that a prospectively planned analysis revealed that in the Phase III trial early weight loss (at least 4 pounds at 1 month) identified patients likely to have greater weight loss after 1 year of treatment. Additional exploratory analyses revealed that patients who appeared to benefit the most from either AXOKINE treatment or a weight reduction program alone were those subjects who lost at least 4 kilograms (8.8 pounds) after 3 months of therapy ("early responders"). The patients who were early responders in the AXOKINE group averaged 14.4 pounds of weight loss at 3 months and 16.6 pounds at 1 year. The early responders in the placebo group had a similar magnitude of average weight loss, but there was a substantially higher fraction of the AXOKINE group (32.2%) than the placebo group (17.6%) who were early responders. The AXOKINE early responder group included both subjects who did and did not develop antibodies to AXOKINE.
Table 1 below summarizes the weight loss results at the end of 1 year of treatment for the early responders in the AXOKINE group compared with those who were not early responders.
Table 1: AXOKINE Early Responders (at least a 4 kilogram weight loss at 3 months) vs. AXOKINE Non-early Responders: Weight loss at 1 year (Intent-to- treat population)
Early Non-early
responders responders
N=472 N=995
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Fraction of total AXOKINE group 32.2% 67.8%
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Average weight loss 16.6 pounds 1.3 pounds
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Average percent weight loss 6.9% 0.6%
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Proportion who lost 5% of weight 54.9% 11.0%
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Proportion who lost 10% of weight 29.2% 2.8%
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"In the United States, 60 million patients suffer from obesity and are therefore at high risk to have a wide variety of ill health effects related to this disease. Given that there is a large target population who might benefit from obesity therapy, and that it is unlikely that any single approach will benefit all individuals, it would be of great value to identify early those individuals most likely to benefit from a particular treatment. Prior data with other obesity therapies indicate that early weight loss is correlated with long-term weight loss. The data from our Phase III study suggest that those individuals most likely to have meaningful weight loss after 1 year are those who demonstrated weight loss early during treatment. This was observed both for individuals on a diet and lifestyle program alone and for those also treated with AXOKINE. AXOKINE treatment increased the proportion of early responders from 17.6% to 32.2% in this study. The early responders achieved meaningful weight loss at 1 year with an average weight loss of 16.6 pounds or a 6.9% reduction in weight. Co-morbidities such as blood pressure, lipids and glycemic control improved as expected given the magnitude of the weight loss in this group. On the other hand, individuals who were not early responders lost only a small amount of weight at 1 year. The approach of treating obese individuals with AXOKINE for 3 months, evaluating their weight loss, and then continuing treatment longer-term for those who are early responders is a paradigm that has the potential to improve the risk benefit profile of AXOKINE," said Dr. Yancopoulos. "We plan to discuss our data and plans with the Food and Drug Administration in the near future."
Phase III Trial Design
The double-blind, randomized, placebo-controlled trial included 501 placebo-treated and 1,467 AXOKINE-treated participants from 65 study sites across the United States. The average baseline weight for all participants was approximately 235 lbs. For 12 months, in addition to counseling in a dietary and lifestyle modification program, subjects received daily subcutaneous injections of either placebo or AXOKINE at a dose of 1.0 microgram per kilogram of body weight. To be included in the study, participants could not have diabetes and had to have a body mass index (BMI) of 30 to 55 without obesity-related risk factors, or 27 to 55 if they had obesity-related risk factors such as high blood pressure or high blood lipids.
BMI is calculated as the weight of an individual in kilograms divided by the square of their height in meters. Normal weight is designated by BMIs of 18.5-24.9, overweight by BMIs of 25-29.9 and obesity by BMIs of 30 and above.
The 12-month treatment period is being followed by a 12-month open-label safety extension phase during which all participants receive AXOKINE and are further monitored for side effects.
AXOKINE Program Next Steps
Regeneron continues to evaluate AXOKINE in the treatment of obese subjects and to further evaluate currently available data from completed trials. Moving forward, the Company plans to work closely with the FDA to review the findings from the recently completed clinical trials and determine whether, and in what manner, to continue with the development of AXOKINE... |
