Arena Pharmaceuticals, Inc. (ARNA)

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Lorcaserin Hydrochloride for Obesity

Lorcaserin hydrochloride, our most advanced drug candidate, is a promising investigative oral treatment for obesity. In September 2006, we initiated a Phase 3 clinical trial program to evaluate the safety and efficacy of lorcaserin for the treatment of obesity. BLOOM (Behavioral modification and Lorcaserin for Overweight and Obesity Management) was the first of three Phase 3 clinical trials in the lorcaserin program. In December 2007, we initiated BLOSSOM (Behavioral modification and LOrcaserin Second Study for Obesity Management) and BLOOM-DM (Behavioral modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus), the second and third Phase 3 clinical trials evaluating lorcaserin's safety and efficacy.

In March 2008 an independent Echocardiographic Safety Monitoring Board, or ESMB, performed a planned detailed review of unblinded echocardiographic data of patients in the BLOOM trial 12 months after enrollment of the last patient. The ESMB's review confirmed that differences, if any, in the Month 12 rates of FDA-defined valvulopathy in patients in the lorcaserin and control groups did not meet their predetermined stopping criteria. Based on the ESMB's review, we have continued the Phase 3 program and have been able to confirm that the statistical power calculations used in the design of the Phase 3 program to monitor patients for increased risk of developing valvulopathy are justified. The findings from the Month 12 review build on the ESMB's September 2007 review that evaluated Month 6 echocardiographic data.

We believe lorcaserin selectively stimulates the 5-HT2C serotonin receptor, a GPCR located in the hypothalamus. Stimulation of this hypothalamic receptor is strongly associated with feeding behavior and satiety. We conducted preclinical studies examining the activity and 5-HT receptor subtype specificity of lorcaserin. In these studies, lorcaserin demonstrated a high affinity and selectivity for the 5-HT2C receptor, with approximately 15-fold and 100-fold selectivity in vitro over the human 5-HT2A and 5-HT2B receptors, respectively, and no pharmacologic activity at other serotonin receptors except at concentrations greatly exceeding the expected therapeutic range.

By preferentially targeting the 5-HT2C receptor, we believe we can help patients effectively lose weight in a safe, well tolerated and efficacious manner. Data from Phase 2 clinical trials of lorcaserin demonstrated that patients who received the drug experienced significantly greater weight loss than patients who received placebo. Lorcaserin has been generally well tolerated at all doses investigated in clinical trials dosing patients up to 12 weeks.

Obesity affects tens of millions of adults and children in the United States and poses serious long-term threats to their health and welfare. Studies have shown that modest weight loss of as little as 5% of initial body weight can result in a meaningful reduction in the risks associated with obesity, such as diabetes. Currently, pharmaceutical treatment options for obesity are limited.

(This page was last updated: August 14, 2008. Additional information regarding Arena is available in its SEC filings.)

http://www.arenapharm.com/wt/page/lho.html