SAN DIEGO, Dec. 13 /PRNewswire-FirstCall/ -- Arena Pharmaceuticals, Inc. announced today positive top-line results from its Phase 2b clinical trial of APD356, Arena's orally administered, internally discovered drug candidate for the treatment of obesity. Over the 12 week treatment period, there was a highly statistically significant (p<0.001) average weight loss of 4.0, 5.7 and 7.9 pounds at daily doses of 10 mg, 15 mg and 20 mg (10 mg dosed twice daily), respectively, in patients taking APD356 compared to 0.7 pounds for the placebo group. APD356 was generally well tolerated at all doses investigated in the trial and there were no apparent effects on heart valves or pulmonary artery pressures. APD356 is a selective agonist of 5-HT2C serotonin receptors, which are located in the hypothalamus, an area of the brain that plays an important role in regulating food intake and metabolism.
"The results of this trial are extremely encouraging and unambiguously support further study of APD356. This trial demonstrated excellent weight loss, particularly considering there was no diet or exercise component in this trial, and the emerging safety and tolerability profile compares favorably with other weight loss drugs," commented Steven Smith, M.D., Principal Investigator and Associate Professor of the Pennington Biomedical Research Center. "Due to the prevalence of obesity and the increased health risks associated with obesity, including increased risk of diabetes, stroke, dyslipidemia and cancer, patients and their physicians have a clear need for therapeutic options that are both safe and efficacious."
The Phase 2b clinical trial was a randomized, double-blinded, dose-ranging study conducted at approximately 40 sites in the United States. The trial enrolled 469 male and female obese patients with a body mass index (BMI) of between 29 and 46. Patients were randomized into four groups to evaluate the safety and efficacy of daily 10 mg, 15 mg and 20 mg (10 mg before breakfast and 10 mg before dinner) doses of APD356 compared to placebo for 12 weeks. The 20 mg dose (10 mg dosed twice daily) was designed to provide similar peak blood levels as the 15 mg once daily dose, but higher blood trough levels, thereby maintaining higher average drug concentrations in the blood. It was also designed to provide a second peak in drug level to cover the evening hours. In addition to standard safety evaluations, patients were assessed by echocardiogram prior to enrollment and at the end of the treatment period. Patients did not receive any diet or exercise advice, but were required to abstain from consuming alcohol during the study.
Patient demographic characteristics at baseline were well balanced across the treatment groups. Eighty-seven percent of participants were women, 53% were Caucasian, 29% were African-American and 18% were Hispanic. At baseline, the average age was 41.5 years, the average weight was 220 pounds, and the average BMI was 36.4.
The primary efficacy endpoint of the Phase 2b study was a reduction in weight in patients completing the 12 week treatment period. Compared to placebo, treatment with APD356 was associated with a highly statistically significant (p<0.001) average weight loss of 4.0, 5.7 and 7.9 pounds at daily doses of 10 mg, 15 mg and 20 mg, respectively, in patients taking APD356 compared to 0.7 pounds for the placebo group.
Weight Change: Day 85 - Baseline (Completer Analysis) Group Mean Weight Change P-value (vs. PBO) (pounds) Placebo (n=88) -0.7 --- 10 mg (n=86) -4.0 P<0.001 15 mg (n=82) -5.7 P<0.001 20 mg (n=77) -7.9 P<0.001
Using an intent-to-treat last observation carried forward (ITT-LOCF) analysis, treatment with APD356 was also associated with a highly statistically significant (p<0.001) average weight loss of 3.7, 4.8 and 6.8 pounds at daily doses of 10 mg, 15 mg and 20 mg, respectively, in patients taking APD356 compared to 0.4 pounds for the placebo group.
Weight Change: Day 85 - Baseline (ITT-LOCF Analysis) Group Mean Weight Change P-value (vs. PBO) (pounds) Placebo (n=116) -0.4 --- 10 mg (n=114) -3.7 P<0.001 15 mg (n=113) -4.8 P<0.001 20 mg (n=110) -6.8 P<0.001
APD356 was generally well tolerated at all doses investigated. Four serious adverse events occurred in the trial: two in the placebo group (pneumonia and kidney stone in a single patient), one in the 10 mg group (major depression, judged unlikely study drug related due to preexisting symptoms) and one in the 20 mg group (new onset seizure, judged unlikely study drug related by a consulting neurologist). Adverse events that occurred in five percent or more of patients in a treatment group are listed below. Adverse events were generally single, self-limited events that were mild or moderate in nature.
APD356-004 Adverse Events >5% in Any Group Event Placebo 10 mg 15 mg 20 mg (n=118) (n=117) (n=118) (n=116) Headache 17.8 % 29.1 % 31.4 % 26.7 % Nausea 3.4 % 7.7 % 8.5 % 11.2 % Dizziness 0 % 5.1 % 7.6 % 7.8 % Vomiting 0.8 % 1.7 % 1.7 % 5.2 % Dry Mouth 0 % 1.7 % 1.7 % 5.2 % Diarrhea 5.9 % 0.9 % 4.2 % 3.4 % Nasopharyngitis 8.5 % 5.1 % 5.9 % 6.0 % Fatigue 2.5 % 4.3 % 5.9 % 3.4 % URI 8.5 % 1.7 % 3.4 % 3.4 % UTI 3.4 % 2.6 % 4.2 % 5.2 %
An assessment of echocardiograms taken at baseline and at the end of the treatment period indicates no apparent APD356 effect on heart valves or pulmonary artery pressures.
"The positive results from this Phase 2b underscore not only the potential of APD356 as a new therapy for the treatment of obesity, but also the ability of Arena to discover and develop novel therapeutics for major diseases," stated Jack Lief, Arena's President and CEO. "As we plan for our end of Phase 2 meeting with the FDA and to move our APD356 program into Phase 3 next year, we will continue to differentiate Arena through excellent research, the diversification and advancement of our pipeline of drug candidates, and an opportunistic but value oriented business and partnering strategy."
About Obesity
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.
About APD356
APD356 is a selective agonist of 5-HT2C serotonin receptors, which are located in the hypothalamus, an area of the brain that plays an important role in regulating food intake and metabolism. Discovered by Arena, APD356 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. It is hypothesized that activation of the 5-HT2B receptor is associated with the cardiac valvulopathy observed with non-selective serotonergic agents. In addition, APD356 has approximately 15-fold selectivity in vitro for the 5-HT2C receptor versus the 5-HT2A receptor. Arena believes that the 5-HT2A receptor contributes to the potential central nervous system adverse effects associated with non-selective serotonergic agents. Arena expects that the selectivity of APD356 will allow the compound to be dosed at a well-tolerated level that will induce clinically relevant weight loss without the cardiac valvular side effects observed with non-selective serotonergic agents previously used in the treatment of obesity.
Arena has issued patents in the U.S. and Europe covering 5-HT2C modulators that include APD356.
Conference Call & Webcast
Arena will host both a conference call and webcast to discuss the APD356 Phase 2b clinical results and provide a corporate update on December 13, 2005, at 5:00 p.m. EST (2:00 p.m. PST). 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 866.711.8198 for domestic callers and 617.597.5327 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 knowledge of GPCRs and its technologies, including CART(TM) (Constitutively Activated Receptor Technology) and Melanophore. Arena has three internally discovered, clinical-stage product candidates. Arena's most advanced clinical compound, APD356, a selective 5-HT2C serotonin receptor agonist for the treatment of obesity is expected to enter Phase 3 in 2006. Arena's lead product candidate for the treatment of insomnia, APD125, a compound with a novel mechanism of action (a selective 5-HT2A receptor inverse agonist), is scheduled to begin a Phase 2 clinical trial by the end of 2005. As part of Arena's collaboration with Merck & Co., Inc., an Arena product candidate for the treatment of atherosclerosis and related disorders is in a Phase 1 clinical trial. Arena also has an active collaboration with Ortho-McNeil, Inc., a Johnson & Johnson company, for the treatment of type 2 diabetes.
Arena Pharmaceuticals(R) and Arena(R) are registered service marks of the company. CART(TM) is an unregistered service mark of the company.
Forward-Looking Statements
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 the results of Arena's Phase 2 clinical trial of APD356, the timing of the end of the Phase 2 meeting with the FDA regarding APD356, the Phase 3 clinical trial of APD356 and the Phase 2 clinical trial of APD125, the tolerability, side effects and efficacy of APD356, the potential commercialization of APD356, and other statements about Arena's strategy, research, pipeline, technologies, preclinical and clinical programs, and ability to discover and develop compounds and commercialize 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 results of Arena's clinical trials, including that the full results of the Phase 2b clinical trial of APD356 may vary from the top-line results, the results of preclinical studies or clinical trials may not be predictive of future results, Arena's ability to partner APD356, APD125 or other of its compounds or programs, the timing, success and cost of Arena's research, out-licensing endeavors and clinical trials, Arena's ability to obtain additional financing, Arena's ability to obtain and defend its patents, 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.
Contacts: Jack Lief Carin Canale President and CEO Atkins + Associates Media & Investor Relations David Walsey (858) 336-3027 Director, Corporate Communications Arena Pharmaceuticals (858) 453-7200, Ext. 1682
Arena Pharmaceuticals, Inc.CONTACT: Jack Lief, President and CEO, or David Walsey, Director,Corporate Communications, both of Arena Pharmaceuticals, +1-858-453-7200,ext. 1682; or Carin Canale, Media & Investor Relations of Atkins +Associates, +1-858-336-3027, for Arena Pharmaceuticals
Web site: http://www.arenapharm.com/
