SAN DIEGO, May 11 /PRNewswire-FirstCall/ -- 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."
Obesity affects tens of millions of adults and children in the U.S. and poses a serious long-term threat to their health and welfare. The number of overweight and obese people has substantially increased over the past several decades. Approximately two-thirds of all adults in the U.S. are obese or overweight. Medical and related costs of obesity in the U.S. were more than $117 billion in 2000. Being obese or overweight is associated with a number of conditions, including heart disease, stroke, diabetes, cancer and osteoarthritis. Medical treatment options for obese and overweight people are currently limited.
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.
Arena holds a patent entitled "5-HT2C Receptor Modulators" granted by the European Patent Office earlier this month. The patent relates to novel compounds that modulate the 5-HT2C serotonin receptor. APD356 is covered under the patent. Arena has a similar patent pending in the United States and elsewhere.
Conference Call & Webcast
Arena will host both a conference call and webcast to discuss the APD356 Phase 2 clinical results and provide a corporate update on May 11, 2005, at 11:00 a.m. EDT (8:00 a.m. PDT). Jack Lief, President and Chief Executive Officer, Dominic P. Behan, Ph.D., Senior Vice President and Chief Scientific Officer, and William R. Shanahan, Jr., M.D., Vice President and Chief Medical Officer, will be present on the conference call.
The conference call can be accessed by dialing 800.329.9097 for domestic callers and 617.614.4929 for international callers. Please specify to the operator that you would like to join the "Arena APD356 conference call." Additionally, the conference call will be webcast live under the investor relations section of Arena's website at http://www.arenapharm.com, and will be archived there for 30 days following the call. Please connect to Arena's website several minutes prior to the start of the conference call to ensure adequate time for any software download that may be necessary.
About Arena Pharmaceuticals
Arena is a clinical-stage biopharmaceutical company focusing on the discovery, development and commercialization of small molecule drugs in four major therapeutic areas: metabolic, cardiovascular, inflammatory and central nervous system diseases. Arena is developing a broad pipeline of compounds that act on an important class of drug targets called G protein-coupled receptors, or GPCRs, using its proprietary technologies, including CART (Constitutively Activated Receptor Technology) and Melanophore. Arena's most advanced clinical compound, APD356, a selective 5-HT2C serotonin receptor agonist for the treatment of obesity, is in Phase 2. Arena is also conducting Phase 1 clinical trials on APD125, a compound with a novel mechanism of action (a selective 5-HT2A receptor antagonist) for the treatment of insomnia. Arena has active collaborations with two major pharmaceutical companies, Ortho- McNeil Pharmaceutical, Inc., a Johnson & Johnson company, for the treatment of type 2 diabetes, and Merck & Co., Inc., for the treatment of atherosclerosis and related disorders.
Arena Pharmaceuticals® and Arena® are registered service marks of the company. CART is an unregistered service mark of the company.
Certain statements in this press release are forward-looking statements that involve a number of risks and uncertainties. Such forward-looking statements include statements about APD356's safety profile, potency and pharmaceutical behavior, expectations for future studies of APD356, the possibility of partnering and ultimately marketing APD356, the pending echocardiograms, and other statements about Arena's strategy, technologies, preclinical and clinical programs, and ability to develop compounds and commercializing drugs. For such statements, Arena claims the protection of the Private Securities Litigation Reform Act of 1995. Actual events or results may differ materially from Arena's expectations. Factors that could cause actual results to differ materially from the forward-looking statements include, but are not limited to, the risk that the results of clinical trials may not be predictive of future results, Arena's ability to partner APD356, the results of any future studies of APD356, the results of echocardiograms, the timing, success and cost of Arena's research, out-licensing endeavors and clinical studies, Arena's ability to obtain additional financing, and the timing and receipt of payments and fees, if any, from Arena's collaborators, including Ortho-McNeil and Merck. Additional factors that could cause actual results to differ materially from those stated or implied by Arena's forward- looking statements are disclosed in Arena's filings with the Securities and Exchange Commission. These forward-looking statements represent Arena's judgment as of the time of this release. Arena disclaims any intent or obligation to update these forward-looking statements, other than as may be required under applicable law.
SOURCE Arena Pharmaceuticals, Inc.
CONTACT: Jack Lief, President and CEO, or David Walsey, Director, Corporate Communications, both of Arena Pharmaceuticals, Inc., +1-858-453-7200; or Susan Neath of Atkins + Associates, +1-858-527-3486, Media & Investor Relations for Arena Pharmaceuticals, Inc.
Web site: http://www.arenapharm.com