WASHINGTON, Oct. 27, 2009 /PRNewswire-FirstCall/ -- Arena Pharmaceuticals, Inc. reported today data from the pivotal BLOSSOM (Behavioral modification and LOrcaserin Second Study for Obesity Management) Phase 3 trial that demonstrate improvements in patients’ body composition, cardiovascular risk factors and quality of life. These findings add to the previously announced top-line BLOSSOM data that showed highly significant weight loss with lorcaserin over one year of treatment in 4,008 patients.
“Safety is of paramount importance in treating patients who are overweight or have obesity,” said Dr. Kaplan. “We need new therapies that help patients reduce their weight and improve cardiovascular factors such as high blood pressure and cholesterol, while avoiding cardiac toxicity and symptoms of depression. Lorcaserin works by selectively affecting a unique and important pathway, which allows for significant weight loss and improvements in these important risk factors, along with an excellent safety and tolerability profile.”
Specifically, the new data demonstrate that treatment with lorcaserin over one year was associated with highly significant improvements or favorable trends compared to placebo in multiple secondary endpoints evaluated in the trial:
Using Intent-to-Treat Last Observation Carried Forward (ITT-LOCF) analysis, lorcaserin patients achieved highly significant improvements in Body Mass Index (BMI), waist circumference and hip circumference. Changes from baseline for patients who took lorcaserin twice daily, lorcaserin once daily or placebo, respectively, were as follows: BMI (kg/m squared), (-2.1, -1.7, -1.0); waist circumference (cm), (-6.2, -5.6, -4.2); and hip circumference (cm), (-5.3, -5.0, -3.3), (p<0.0001) compared to placebo for all measurements. In addition, lorcaserin patients lost significantly more body fat than the placebo patients.
Using ITT-LOCF analysis, lorcaserin helped improve patients’ cardiovascular risk factors. Patients dosed with 10 mg of lorcaserin once or twice daily achieved statistical significance (p<0.05) versus placebo at Week 52 for percent change in HDL cholesterol and triglycerides and achieved favorable trends in total cholesterol and LDL cholesterol. Lorcaserin did not increase blood pressure or heart rate at any time point. Changes from baseline for patients who took lorcaserin twice daily, lorcaserin once daily or placebo, respectively, were as follows: diastolic blood pressure (mmHg), (-1.9, -1.0, -1.9); systolic blood pressure (mmHg), (-2.0, -1.1, -1.2); and heart rate (bpm), (-2.3, -1.1, -1.6).
Lorcaserin did not increase depression or suicidal ideation compared to placebo. Adverse events related to depression and their rates for patients who took lorcaserin twice daily, lorcaserin once daily or placebo, respectively, were as follows: depression (1.9%, 1.1%, 1.8%); depressed mood (0.6%, 0.9%, 0.9%); and depressive symptoms (<0.1%, 0%, 0%).
“Our team at Arena has worked diligently to discover and develop a novel treatment for weight management that delivers the combination of efficacy, safety and tolerability. Lorcaserin patients in the pivotal program achieved meaningful weight loss and improvements in important secondary endpoints,” said Jack Lief, Arena’s President and Chief Executive Officer. “The Obesity Society meeting provides us with an outstanding opportunity to discuss lorcaserin’s profile with the enthusiastic physicians who are in need of promising, new treatment options.”
Lorcaserin was very well tolerated. Adverse events that exceeded placebo by greater than 3% and their rates for patients who took lorcaserin twice daily, lorcaserin once daily or placebo, respectively, were as follows: headache (15.6%, 15.6%, 9.2%); nausea (9.1%, 7.6%, 5.3%); dizziness (8.7%, 6.2%, 3.9%); fatigue (8.4%, 6.6%, 4.1%); and dry mouth ( 5.4%, 3.4%, 2.3%). Serious adverse events occurred infrequently and their rates for patients who took lorcaserin twice daily, lorcaserin once daily or placebo, respectively, were as follows: 3.1%, 3.4% and 2.2%.
The assessment of echocardiograms performed at baseline and after patients completed 6 and 12 months of dosing indicated that lorcaserin did not increase echocardiographic heart valve regurgitation. Lorcaserin met the primary safety endpoint that evaluated the rates of new FDA-defined valvulopathy in BLOSSOM at Week 52: lorcaserin 10 mg twice daily (2.0%), 10 mg once daily (1.4%) and placebo (2.0%). The integrated BLOOM (Behavioral modification and Lorcaserin for Overweight and Obesity Management) and BLOSSOM echocardiography data set rules out a risk of valvulopathy in lorcaserin patients according to criteria requested by the FDA.
Previously Announced Efficacy Data
Patient Disposition
BLOSSOM Trial Design
Phase 3 Program Overview
A standardized program of moderate diet and exercise guidance is included in the Phase 3 program. The program’s hierarchically ordered co-primary efficacy endpoints are: the proportion of patients achieving 5% or greater weight loss after 12 months, the difference in mean weight loss compared to placebo after 12 months, and the proportion of patients achieving 10% or greater weight loss after 12 months. Arena is also studying several key secondary endpoints, including changes in serum lipids, markers of inflammation and insulin resistance, and in the BLOOM-DM trial, other indicators of glycemic control.
Lorcaserin is a novel single agent that represents the first in a new class of selective serotonin 2C receptor agonists. The serotonin 2C receptor is expressed in the brain, including the hypothalamus, an area involved in the control of appetite and metabolism. Stimulation of this receptor is strongly associated with feeding behavior and satiety. Arena has patents that cover lorcaserin in the US and other jurisdictions, which in most cases are capable of continuing into 2023 without taking into account any patent term extensions or other exclusivity Arena might obtain.
The National Institutes of Health reported in 2007 that about 65% of US adults are overweight or obese. A 2009 publication in Health Affairs estimated the annual medical burden of obesity in the US to be $147 billion in 2008. Studies have shown that weight loss of 5% to 10% is medically significant and results in meaningful improvements in cardiovascular risk factors and a significant reduction in the incidence of type 2 diabetes in patients with glucose intolerance.
Arena is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing oral drugs in four major therapeutic areas: cardiovascular, central nervous system, inflammatory and metabolic diseases. Arena’s most advanced drug candidate, lorcaserin, is being investigated in a Phase 3 clinical trial program for weight management. Arena has a broad pipeline of novel compounds targeting G protein-coupled receptors, an important class of validated drug targets, which includes compounds being evaluated independently and with partners, including Merck & Co., Inc., and Ortho-McNeil-Janssen Pharmaceuticals, Inc.
Forward-Looking Statements
Arena Pharmaceuticals, Inc.
