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.
We are continuing the Phase 3 program following a planned detailed review in March 2008 by an independent Echocardiographic Safety Monitoring Board, or ESMB, of unblinded echocardiographic data performed after patients in the BLOOM trial completed 12 months of dosing in the trial. The ESMB's review confirmed that differences, if any, in the rates of FDA-defined valvulopathy in patients treated with lorcaserin and in the control group did not meet their predetermined stopping criteria. Based on the ESMB's review of the rate of FDA-defined valvulopathy, we 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 echocardiograms after patients completed six months of dosing.
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.
Our product candidates have not been approved by the U.S. Food and Drug Administration or any international regulatory agency.
(NOTE: This page was last updated: June 5, 2008.)
