Obesity
Positive Clinical Trial Results of Novel Anti-Obesity Compound
By Arena Pharmaceuticals, Inc.
May 12, 2005, 18:09

Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) announced today positive top-line results from its Phase 2 clinical trial of APD356, Arena's orally administered, internally discovered drug candidate for the treatment of obesity. Over the 28 day treatment period, there was a highly statistically significant (p=.0002) average weight loss of 2.9 pounds in patients taking the 15 mg dose of APD356 versus 0.7 pounds for the placebo group. APD356 was generally well tolerated at all doses investigated in the trial. APD356 is a selective agonist of 5-HT2C serotonin receptors, which are located in the hypothalamus, an area of the brain known to play an important role in regulating food intake and metabolism.

"The prevalence of obesity has increased substantially in recent years and has reached alarming rates. Obesity is a serious health risk and is associated with several conditions, including diabetes, stroke and heart disease. Patients and their physicians need novel methods to treat obesity," stated Steven Smith, M.D., Principal Investigator and Associate Professor of the Pennington Biomedical Research Center. "The results of this trial are very supportive of further study and provide hope that obese individuals could have a new therapeutic option in the future to help control their weight in an effective, safe and controlled manner."

This Phase 2 clinical trial of APD356 was a randomized, double-blinded, multiple-dose study examining 352 obese volunteers at 24 clinical sites in the United States. The trial was to enroll otherwise healthy male and female patients with a body mass index (BMI) of between 30 and 45. Patients were randomized into four groups to compare doses of 1, 5 and 15 mg of APD356 versus placebo. The trial evaluated safety and weight loss after oral administration of APD356 once daily for 28 days. The trial protocol provided that patients should maintain their normal diet and level of activity, but required that patients abstain from consuming alcohol. In addition to standard safety evaluations, patients were assessed by echocardiogram upon enrollment, and were scheduled for follow-up echocardiograms at 29 and 90 days after receiving their first dose.

Patient demographic characteristics at baseline were well balanced across treatment groups. Eighty percent of participants were women, 55% were Caucasian, 25% African-American and 18% Hispanic. At baseline, the average age was 40 years, the average weight was 223 pounds (range 158-468 pounds), and the average BMI was 36.

The primary efficacy endpoint of the Phase 2 study was a reduction in weight in patients completing the 28 day treatment period (Day 29). Compared to placebo, treatment with APD356 was associated with a highly statistically significant average weight loss of 2.9 pounds in the 15 mg group versus 0.7 pounds in the placebo group. No statistically significant weight loss was observed in the 1 mg or 5 mg groups. Similar results were observed in the intent-to-treat, last observation carried forward (LOCF) analysis. The table below summarizes the mean weight change for all patients completing the study in each group.


Group Mean Weight Change p value
from Baseline
(pounds) (relative to placebo)

Placebo (n=71) -0.7 --
1.0 mg (n=75) -0.7 Not statistically significant
5.0 mg (n=72) -0.9 Not statistically significant
15.0 mg (n=69) -2.9 p = 0.0002



APD356 was generally well tolerated at all doses investigated, and there were no serious adverse events in the trial. Events that occurred in 5% or more of patients in a treatment group are listed below.


Event Placebo 1 mg 5 mg 15 mg

Nausea 3.5% 5.6% 5.6% 6.9%
Nasopharyngitis 5.8% 4.4% 3.4% 1.1%
Headache 14.0% 15.6% 7.9% 20.7%
Cough 1.2% 5.6% 2.2% 1.1%



There was no apparent drug effect on the heart as assessed by Day 29 echocardiograms. Post day 29 echocardiograms are pending.

"All of us at Arena are excited with these results, and we would like to thank all the patients, clinicians and nurses participating in our study. We intend to use these results to build on our APD356 clinical program and soon initiate a Phase 2b trial enrolling approximately 300 to 400 patients in a study designed to investigate the efficacy and safety of APD356 over a three- month period," stated Jack Lief, Arena's President and CEO. "In addition to supporting the continued development of APD356, these top-line results should strongly support our partnering efforts and further validate our research and development capabilities."

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