Positive Phase 2 clinical trial results reported for novel anti-obesity compound
Drug News -- May 11, 2005
News: Positive Phase 2 clinical trial results reported for novel anti-obesity compound APD356
SAN DIEGO, CALIF., May 11, 2005 --Arena Pharmaceuticals announced positive top-line results from its Phase 2 clinical trial of APD356, the company'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.
APD356 was generally well tolerated at all doses investigated, and there were no serious adverse events in the trial. There was no apparent drug effect on the heart as assessed by Day 29 echocardiograms. Post day 29 echocardiograms are pending.
Stimulation of the 5-HT2C receptor is thought to play an important role in food intake. APD356, discovered by Arena, is intended to selectively stimulate the 5-HT2C receptor and has approximately 100-fold selectivity in vitro for the 5-HT2C receptor relative to the 5-HT2B receptor. Arena believes the 5-HT2B receptor is primarily implicated in the cardiac valvulopathy observed with non-selective serotonergic drugs. In addition, APD356 has approximately 15-fold selectivity in vitro for the 5-HT2C receptor versus the 5-HT2A receptor, thought to be primarily responsible for most of the central nervous system adverse effects of non-selective serotonergic agents. Arena believes that the selectivity of APD356 may allow the compound to be dosed at a well-tolerated level that will induce clinically relevant weight loss without the side effects observed with non-selective serotonergic agents.
More information is available at http://www.arenapharm.com
Source: Arena Pharmaceuticals
Posted: May 2005