Arena Pharmaceuticals Announces Lorcaserin Data Demonstrating Highly Significant Categorical and Absolute Weight Loss and Improvements in Secondary Endpoints Associated with Cardiovascular Risk
-- Late-Breaking Data from Pivotal BLOOM Trial Presented at the American Diabetes Association's 69th Scientific Sessions Expand on Previously Announced Positive Top-Line Results -
NEW ORLEANS, June 6, 2009 /PRNewswire-FirstCall via COMTEX News Network/ -- Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) announced today a late-breaking poster presentation of positive results from BLOOM (Behavioral modification and Lorcaserin for Overweight and Obesity Management), the first of two pivotal trials evaluating the safety and efficacy of lorcaserin for weight management, at the American Diabetes Association's 69th Scientific Sessions. Lorcaserin patients achieved highly significant categorical and absolute weight loss in Year 1, and continued treatment with lorcaserin in Year 2 helped significantly more patients maintain their weight loss as compared to those on placebo. Treatment with lorcaserin also resulted in highly significant improvements as compared to placebo in multiple secondary endpoints associated with cardiovascular risk. Lorcaserin did not result in increased risk of depression and was not associated with the development of cardiac valvular insufficiency.
Previously announced BLOOM data demonstrated that lorcaserin was highly efficacious, achieving statistical significance on all three co-primary efficacy endpoints, and was very well tolerated. The BLOOM results also satisfy the efficacy requirement in the most recent US Food and Drug Administration, or FDA, draft guidance for the development of drugs for weight management.
"These data provide reason for new optimism for the millions of people who struggle with managing their weight and are in need of novel, well tolerated treatments to help improve their overall health," said Steven R. Smith, M.D., Co-Principal Investigator and Professor and Assistant Director for Clinical Research at the Pennington Biomedical Research Center. "Lorcaserin's positive impact on multiple secondary measures has important implications for improving co-morbidities associated with excess weight and further demonstrates the medically significant benefits of 5% or more weight loss, a mark two-thirds of the lorcaserin patients who completed the BLOOM trial achieved."
"Given the positive lorcaserin BLOOM results, we are focused on partnering efforts and realizing lorcaserin's significant commercial potential," stated Jack Lief, Arena's President and Chief Executive Officer.
Per Protocol Efficacy
In addition to supporting the previously announced results on all three co-primary endpoints on an intent-to-treat, last observation carried forward (ITT-LOCF) basis, the data presented today demonstrated strong efficacy in patients who completed one year of treatment according to the trial's protocol. In the per protocol population, nearly two-thirds (66.4%) of lorcaserin patients lost at least 5% of their weight compared to 32.1% of patients on placebo (p<0.0001), and over one-third (36.2%) of lorcaserin patients lost at least 10% of their weight compared to 13.6% for placebo (p<0.0001). The average weight loss in this population was 17.9 pounds in the lorcaserin group, compared to 7.4 pounds in the placebo group. Patients randomized to remain on lorcaserin for Year 2 maintained a significantly greater amount of weight loss compared to the lorcaserin patients who switched to placebo at Week 52 in both the ITT-LOCF and per protocol populations.
Secondary Endpoint Analysis
New data demonstrate that treatment with lorcaserin over one year was associated with highly significant improvements compared to placebo in multiple secondary endpoints associated with cardiovascular risk, including:
-- Blood Pressure: systolic blood pressure, diastolic blood pressure and
-- Lipids: total cholesterol, LDL cholesterol and triglycerides
-- Glycemic Parameters: fasting glucose, fasting insulin and insulin
-- Inflammatory Markers of Cardiovascular Risk: high-sensitivity CRP and
Quality of Life, as assessed by the Impact of Weight Questionnaire - Lite, also improved to a significantly greater extent in the lorcaserin group than the placebo group at Week 52.
"We are pleased to present the BLOOM data in a scientific forum. In this trial, lorcaserin helped patients rapidly lose weight and keep it off in a well-tolerated manner," said William R. Shanahan, M.D., Arena's Vice President and Chief Medical Officer. "We believe that lorcaserin's overall safety profile along with the significant improvements seen in important secondary endpoints associated with cardiovascular risk will be supportive of the approval process. We look forward to announcing our BLOSSOM data in September and completing our NDA submission by the end of the year."
Safety and Tolerability Profile
Lorcaserin was very well tolerated. Discontinuation rates for adverse events were similar in the lorcaserin and placebo groups for Year 1 and Year 2 (7.1% vs. 6.7% and 3.0% vs. 3.0%, respectively).
In addition to the previously announced tolerability data, today's presentation also reported that lorcaserin demonstrated no increase in depression or suicidal ideation compared to placebo. Depression adverse events were measured using a Standard MedDRA Query for adverse event terms related to depression (e.g. depression, depressed mood, crying, decreased interest, etc.). Overall, the rate of depression-related events was low and rates were comparable in patients who took lorcaserin and placebo. Suicidal ideation was prospectively evaluated by administration of the Beck Depression Inventory-II. Overall, the rate of suicidal ideation was low and similar numbers of patients on lorcaserin and placebo reported suicidal thoughts during Year 1 and Year 2.
Using an LOCF analysis for each year, the assessment of echocardiograms performed at baseline and after patients completed 6, 12, 18 and 24 months of dosing indicated that lorcaserin was not associated with valvular insufficiency: during two years of use, rates of change in individual regurgitant scores and the development of FDA-defined valvulopathy (moderate or greater mitral insufficiency and/or mild or greater aortic insufficiency) were similar between treatment groups.
Lorcaserin met the primary safety endpoint of no significant difference in rates of valvulopathy at 12 months. Rates of valvulopathy at 6, 12, 18 and 24 months for lorcaserin versus placebo were 2.1% vs. 1.9% (p=0.88), 2.7% vs. 2.3% (p=0.70), 2.9% vs. 3.1% (p=0.86) and 2.6% vs. 2.7% (p=1.00). At 18 and 24 months, rates of valvulopathy for lorcaserin patients crossing over to placebo were 3.6% and 1.9%, respectively.
In addition, similar numbers of mitral insufficiency shifts and aortic insufficiency shifts in Year 1 and Year 2 were reported for patients on lorcaserin and placebo.
The FDA previously requested that Arena rule out a 1.5-fold or greater risk of valvulopathy with 80% power. Assuming similar results in Arena's final pivotal trial, BLOSSOM (Behavioral modification and LOrcaserin Second Study for Obesity Management), the integrated data set from the two trials will be more than sufficiently large to meet this requirement.
BLOOM Trial Design
BLOOM, the first of three lorcaserin Phase 3 trials, is a double-blind, randomized, placebo-controlled trial involving 3,182 patients in approximately 100 sites in the US. The trial evaluated 10 mg of lorcaserin dosed twice daily versus placebo over a two-year treatment period in obese patients (Body Mass Index, or BMI, 30 to 45) with or without co-morbid conditions and overweight patients (BMI 27 to less than 30) with at least one co-morbid condition. The trial did not include any dose titration or run-in period. Patients were randomized in a 1:1 ratio to lorcaserin or placebo at baseline. At Week 52, 856 patients taking lorcaserin were re-randomized in a 2:1 ratio to continue lorcaserin or to switch to placebo, and 697 patients on placebo were continued on placebo. Patients received echocardiograms at screening, and at 6, 12, 18 and 24 months after initiating dosing in the trial; patients with FDA-defined valvulopathy were excluded from enrolling in the trial.
Phase 3 Program Overview
The Phase 3 program consists of three trials, BLOOM, BLOSSOM and BLOOM-DM (Behavioral modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus), and is planned to enroll a total of approximately 7,800 patients. BLOOM and BLOSSOM comprise the Phase 3 pivotal registration program. BLOSSOM has enrolled 4,008 patients and is evaluating 10 mg of lorcaserin dosed once or twice daily versus placebo over a one-year treatment period in obese patients with or without co-morbid conditions and overweight patients with at least one co-morbid condition at about 100 sites in the US. BLOOM-DM is expected to complete enrollment around the end of June and is evaluating 10 mg of lorcaserin dosed once or twice daily versus placebo over a one-year treatment period in obese and overweight patients with type 2 diabetes at about 60 sites in the US. Approximately 600 patients are expected to be enrolled in BLOOM-DM, which is planned as a supplement to the lorcaserin NDA.
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. In BLOSSOM and BLOOM-DM all patients will receive echocardiograms at baseline, at month 6, and at the end of the study to assess heart valve function over time. In contrast to the BLOOM trial, however, there are no echocardiographic exclusion criteria for entry into these trials and there is no monitoring by an independent board.
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 located in areas of the brain involved in the control of appetite and metabolism, such as the hypothalamus. Stimulation of this receptor is strongly associated with feeding behavior and satiety. Lorcaserin is currently being evaluated in a Phase 3 program expected to enroll approximately 7,800 patients and potentially represents a targeted treatment option for the millions of patients who need to better manage their weight. 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. Medical and related costs of obesity to the US are $123 billion per year according to a 2005 report by the International Diabetes Federation. 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. Diet and exercise should form the basis of healthy weight loss, but pharmaceutical treatment options for obesity are currently limited for the many patients that require additional help in achieving and maintaining medically important weight loss.
About the FDA Draft Guidance
The FDA draft guidance document for developing products for weight management dated February 2007 provides recommendations regarding the development of drugs for the indication of weight management. It contains two alternate efficacy benchmarks, only one of which needs to be met for approval. The guidance provides that, in general, a product can be considered effective for weight management if after one year of treatment either of the following occurs: (1) the difference in mean weight loss between the active-product and placebo-treated groups is at least 5% and the difference is statistically significant, or (2) the proportion of subjects who lose greater than or equal to 5% of baseline body weight in the active-product group is at least 35%, is approximately double the proportion in the placebo-treated group, and the difference between groups is statistically significant.
About Arena Pharmaceuticals
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's broad pipeline of novel compounds target G protein-coupled receptors, an important class of validated drug targets, and includes compounds being evaluated independently and with partners, including Merck & Co., Inc., and Ortho-McNeil-Janssen Pharmaceuticals, Inc.
Arena Pharmaceuticals(R) and Arena(R) are registered service marks of the company. "APD" is an abbreviation for Arena Pharmaceuticals Development.
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 BLOOM results; the development, advancement, therapeutic indication, tolerability, safety, selectivity and efficacy of lorcaserin; the FDA's guidance, process and requirements; the potential of the lorcaserin Phase 3 program and its results to meet the FDA's approval requirements, including with regard to assessing the risk of developing valvulopathy; the approval of lorcaserin for marketing; lorcaserin's partnering, commercial and other potential; the protocol, design, scope, enrollment and other aspects of the lorcaserin trials; future activities, results and announcements relating to lorcaserin, including the BLOSSOM results, the submission of an NDA for lorcaserin and the submission of the BLOOM-DM results as a supplement to the NDA; the potential of lorcaserin in managing weight, improving health and generating patient interest; the impact of weight loss on health, including improving co-morbidities and providing other medically significant benefits; lorcaserin's patent coverage; and Arena's focus, strategy, internal and partnered 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, Arena's ability to obtain additional funds; the timing, success and cost of Arena's lorcaserin program and other of its research and development programs; results of clinical trials or preclinical studies may not be predictive of future results; clinical trials and studies may not proceed at the time or in the manner Arena expects or at all; Arena's ability to partner lorcaserin or other of its compounds or programs; the timing and ability of Arena to receive regulatory approval for its drug candidates; 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.