• E-mail
• Print
• Comment
• Font Size
• Digg
• del.icio.us
• Discuss article

Arena Pharmaceuticals' Lorcaserin Hydrochloride Phase 2b Study Results Demonstrate Significant Weight Loss and Positive Effect on BMI and Waist and Hip Circumference in Obese Patients

Posted on: Monday, 12 June 2006, 18:00 CDT

WASHINGTON, June 12 /PRNewswire-FirstCall/ -- Arena Pharmaceuticals, Inc. announced today that Steven Smith, M.D., principal investigator in the study and associate professor and chief, in-patient unit of the Pennington Biomedical Research Center is presenting data from Arena's positive Phase 2b clinical trial of lorcaserin hydrochloride (formerly APD356) for the treatment of obesity in an oral presentation at the 66th Annual Scientific Sessions of the American Diabetes Association (ADA) in Washington, DC. When compared to placebo, patients treated with lorcaserin experienced a highly statistically significant average weight loss and reductions in other physical measures, including body mass index (BMI) and waist and hip circumference. Trends or improvements were seen in fasting glucose and most lipid measures despite normal mean baseline values and the relatively short study duration.

"Lorcaserin demonstrated excellent weight loss in this study, coupled with excellent tolerability and a positive impact on associated physical measures and most lipid parameters in obese patients," stated Steven Smith, M.D., principal investigator in the study and associate professor and chief, in-patient unit of the Pennington Biomedical Research Center. "More than 60 million Americans are obese, leaving them at increased risk of diabetes, heart attack, stroke, dyslipidemia and cancer. Currently available treatments are limited and new therapies are needed that can provide safe and effective long-term weight loss."

"Discovered through Arena's proprietary platform, lorcaserin is a highly selective compound which works on a specific serotonin receptor located in the hypothalamus, an area of the brain known to impact satiety and influence metabolic rate," stated Jack Lief, Arena's President and CEO. "Based on the strength of these data, we are currently in discussions with the FDA about initiating a Phase 3 trial of lorcaserin in obese patients later this year."

Lorcaserin Phase 2b Study Results

Patients completing the twelve-week treatment period with lorcaserin achieved a highly statistically significant (p<0.001) mean 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, compared to 0.7 pounds for the placebo group. Using an intent-to-treat, last-observation-carried-forward (ITT-LOCF) analysis, treatment with lorcaserin 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 lorcaserin compared to 0.4 pounds for the placebo group.

The proportions of patients completing the twelve week treatment period with lorcaserin who achieved a 5% or greater weight loss from baseline were 13% (p=0.015), 20% (p<0.001) and 31% (p<0.001) at daily doses of 10 mg, 15 mg and 20 mg, respectively, compared to 2% in the placebo group. As in the prior Phase 2a clinical trial, weight loss was progressive.

Treatment with lorcaserin was also associated with dose-dependent and statistically significant improvements in BMI (p<0.001 for all three doses), waist circumference (p=0.017 for the 15 mg dose; p=0.001 for the 20 mg dose), hip circumference, (p=0.017 for the 20 mg dose), cholesterol (p=0.019 for the 15 mg dose; p=0.006 (-3.7%) for the 20 mg dose), and fasting blood sugar (p=0.028 (-3.0%) for the 20 mg dose). Positive, dose-dependent trends on LDL-cholesterol and triglycerides were also observed, and there was no apparent effect on blood pressure.

A small, non-dose dependent decrease of 3.3-3.5% was observed in HDL levels that was marginally statistically significant at all doses (p=0.038-0.053). The decrease in HDL levels resulted in slight increases in LDL:HDL ratios, which were also non-dose dependent and not statistically significant. A similar small increase was also observed in the placebo group.

Lorcaserin was generally well tolerated at all doses investigated in the trial. Adverse events occurring in greater than 5% in any of the dosed groups were headache, nausea, dizziness, vomiting, dry mouth, nasopharyngitis, fatigue and urinary tract infection.

An assessment of baseline and Day 85 echocardiograms indicated no apparent lorcaserin effect on heart valves or pulmonary artery pressure. No changes in valvular regurgitation greater than one category, no significant differences between any treatment group and placebo in number of increases in valve regurgitation at any valve, and no significant increases in pulmonary artery pressure in any group were identified in the echocardiogram results.

Lorcaserin Phase 2b Study Design

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 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 dosed twice daily) doses of lorcaserin compared to placebo for 12 weeks. The primary efficacy endpoint of the Phase 2b study was a reduction in weight in patients completing the 12 week treatment period. 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.

A complete set of the slides presented today at the ADA annual meeting will be available on the investor relations section of the Arena website at http://www.arenapharm.com/.

About Lorcaserin Hydrochloride

Lorcaserin hydrochloride stimulates the 5-HT2C serotonin receptor, located in the part of the brain called the hypothalamus, which helps regulate satiety and influences metabolic rate. Lorcaserin 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 agents. In addition, lorcaserin has approximately 15-fold selectivity in vitro for the 5-HT2C receptor versus the 5-HT2A receptor, a central nervous system (CNS) receptor thought to be responsible for many of the CNS adverse effects of non-selective serotonergic agents.

Arena holds similar patents entitled "5-HT2C Receptor Modulators" granted by both the U.S. Patent and Trademark Office and the European Patent Office. The patents relate to novel compounds that modulate the 5-HT2C serotonin receptor. Lorcaserin is covered under the patents.

About Obesity

Obesity affects tens of millions of adults and children in the United States 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 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, central nervous system, cardiovascular and inflammatory diseases. Arena is developing a broad pipeline of compounds targeting 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 four internally discovered, clinical-stage drug candidates for major diseases. The most advanced is lorcaserin hydrochloride, a selective 5-HT2C serotonin receptor agonist that is under investigation for the treatment of obesity and is expected to enter Phase 3 clinical development in the second half of 2006. Arena's lead drug candidate for the treatment of insomnia, APD125, is a compound with a novel mechanism of action (a selective 5-HT2A receptor inverse agonist) with an IND pending before the FDA for the initiation of a Phase 2 trial in patients with chronic insomnia. Arena also has two clinical-stage collaborations with major pharmaceutical companies: Merck & Co., Inc., began a Phase 2 clinical trial of MK-0354, an Arena discovered drug candidate for the treatment of atherosclerosis and related disorders, in the second quarter of 2006; and Ortho-McNeil, Inc., a Johnson & Johnson company, began a Phase 1 clinical trial of APD668, an Arena discovered drug candidate for the treatment of type 2 diabetes, in the first quarter of 2006.

Arena Pharmaceuticals(R) and Arena(R) are registered service marks of the company. CART(TM) is an unregistered service mark of the company. "APD" is an abbreviation for Arena Pharmaceuticals Development.

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 trials of lorcaserin hydrochloride, the tolerability, side effects and efficacy of lorcaserin hydrochloride, the expected clinical trials of lorcaserin hydrochloride and APD125, the potential of lorcaserin hydrochloride to help satisfy a need for new therapies that can provide safe and effective long-term weight loss, and other statements about Arena's strategy, technologies, preclinical and internal and partnered clinical programs, and ability to 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 FDA may not allow Arena's planned clinical trials to proceed at the time Arena expects or at all, the results of preclinical studies or clinical trials may not be predictive of future results, Arena's ability to partner lorcaserin hydrochloride, 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. 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 President and CEO David Walsey Director, Corporate Communications Arena Pharmaceuticals 858.531.7778 Carolyn Wang WeissComm Partners Media Relations 415.225.5050 http://www.arenapharm.com/

Arena Pharmaceuticals, Inc.

CONTACT: Jack Lief, President and CEO, or David Walsey, Director,Corporate Communications, both of Arena Pharmaceuticals, +1-858-531-7778; orMedia, Carolyn Wang of WeissComm Partners, +1-415-225-5050, for ArenaPharmaceuticals, Inc.

Web site: http://www.arenapharm.com/

Source: PRNewswire-FirstCall

More News in this Category