Arena Pharmaceuticals Announces Positive Lorcaserin Pivotal Phase 3 Obesity Trial Results: Meets All Primary Efficacy and Safety Endpoints
-- Lorcaserin Very Well Tolerated Throughout Two-Year Study
-- Conference Call Scheduled for Today at 8:30 a.m. EDT
SAN DIEGO, March 30, 2009 /PRNewswire-FirstCall via COMTEX News Network/ -- Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) announced today positive top-line 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. Statistical significance (p<0.0001) was achieved on all three of the hierarchically ordered co-primary endpoints for patients treated with lorcaserin versus placebo. Treatment with lorcaserin was generally very well tolerated. An assessment of echocardiograms indicates no apparent drug-related effect on the development of US Food and Drug Administration (FDA)-defined valvulopathy over the two-year treatment period.
Primary Endpoint Analysis
The hierarchically ordered endpoints were 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. Compared to placebo, using an intent-to-treat last observation carried forward (ITT-LOCF) analysis, treatment with lorcaserin was associated with highly statistically significant (p<0.0001) categorical and average weight loss from baseline after 12 months:
-- 47.5% of lorcaserin patients lost greater than or equal to 5% of their
body weight from baseline compared to 20.3% in the placebo group. This
result satisfies the efficacy benchmark in the most recent FDA draft
-- Average weight loss of 5.8% of body weight, or 12.7 pounds, was achieved
in the lorcaserin group, compared to 2.2% of body weight, or 4.7 pounds,
in the placebo group. Statistical separation from placebo was observed
by Week 2, the first post-baseline measurement.
-- 22.6% of lorcaserin patients lost greater than or equal to 10% of their
body weight from baseline, compared to 7.7% in the placebo group.
Lorcaserin patients who completed 52 weeks of treatment according to the protocol lost an average of 8.2% of body weight, or 17.9 pounds, compared to 3.4%, or 7.3 pounds, in the placebo group (p<0.0001).
"The BLOOM results, demonstrating lorcaserin's medically important weight loss coupled with the tolerability and safety profile displayed in this trial, differentiate lorcaserin from approved drugs or other agents in clinical trials," commented Steven R. Smith, M.D., Co-Principal Investigator and Professor and Assistant Director for Clinical Research at the Pennington Biomedical Research Center. "Obesity is a widespread disease; having a well tolerated and effective therapy that can be used by the majority of patients who need weight reduction could also have beneficial effects on co-morbid conditions, such as diabetes, lipid disorders, and cardiovascular disease."
Safety and Tolerability Profile
Lorcaserin was generally very well tolerated. The most frequent adverse events reported in Year 1 and their rates for lorcaserin and placebo patients, respectively, were as follows: headache (18.0% vs. 11.0%), upper respiratory tract infection (14.8% vs. 11.9%), nasopharyngitis (13.4% vs. 12.0%), sinusitis (7.2% vs. 8.2%) and nausea (7.5% vs. 5.4%). The most frequent adverse events reported in Year 2 and their rates for lorcaserin and placebo patients, respectively, were as follows: upper respiratory tract infection (14.5% vs. 16.1%), nasopharyngitis (16.4% vs. 12.6%), sinusitis (8.6% vs. 6.9%), arthralgia (6.6% vs. 6.2%) and influenza (6.6% vs. 6.0%). In patients crossing over from lorcaserin to placebo after Year 1, the rates of these Year 2 adverse events were: 11.0%, 13.8%, 10.6%, 6.0% and 4.9%, respectively.
Adverse events of depression, anxiety and suicidal ideation were infrequent and reported at a similar rate in each treatment group, and no seizures were reported. Serious adverse events occurred with similar frequency in each group throughout the trial without apparent relationship to lorcaserin. One death occurred during the trial, which was a patient in the placebo arm.
"The BLOOM trial, having met all of its primary endpoints and the FDA categorical efficacy benchmark as stated in their guidance, suggests lorcaserin has the potential to become the first in a new class of effective and very well tolerated weight management therapeutics that selectively target the serotonin 2C receptor," said William R. Shanahan, M.D., Arena's Vice President and Chief Medical Officer. "We look forward to building on these positive top-line data with the BLOSSOM study results expected around the end of September leading to an NDA submission by the end of this year. We also look forward to working with the FDA during the approval process to bring this treatment to patients in need of new options."
Using an ITT-LOCF analysis, the assessment of echocardiograms performed at baseline and after patients completed 6, 12, 18 and 24 months of dosing indicated no apparent drug-related effect on the development of FDA-defined valvulopathy (moderate or greater mitral insufficiency and/or mild or greater aortic insufficiency).
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%, 2.7% vs. 2.3%, 2.9% vs. 3.1% and 2.6% vs. 2.7%. At 18 and 24 months, rates of valvulopathy for lorcaserin patients crossing over to placebo were 3.6% and 1.9%, respectively.
The FDA has requested that Arena rule out a 1.5-fold or greater risk of valvulopathy with 80% power. Assuming similar results in 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.
"The echocardiographic safety data is very reassuring," commented Neil J. Weissman, M.D., Co-Principal Investigator, Director, Cardiac Ultrasound and Ultrasound Core Labs, President, MedStar Research Institute, and Professor of Medicine, Georgetown University. "In this double-blind, prospective study, there was no evidence of a difference in the development of valve disease in the large number of patients on lorcaserin versus control for up to two years of continuous use. No prospective valvulopathy trial has ever studied this many patients for this period of time, particularly under such well-controlled circumstances."
Secondary Endpoint Analysis
Treatment with lorcaserin was also associated with statistically significant improvements (ITT-LOCF) in a range of secondary endpoints compared to treatment with placebo, including:
Changes in HDL cholesterol were similar in the two groups. Analysis of the above and additional endpoints, including glucose, insulin and waist circumference, is ongoing and will be announced at a later date.
During Year 2 of the trial, patients continuing on lorcaserin were better able to maintain more of the Week 52 weight loss than Year 1 lorcaserin patients re-randomized to placebo in Year 2.
Patient demographic characteristics at baseline were well balanced across the treatment groups. The Week 52 completion rate was higher for patients on lorcaserin (55.4%) compared to those on placebo (45.1%). The difference is primarily attributed to higher discontinuation rates for "Subject Decision" (19.2% lorcaserin vs. 27.7% placebo), which includes "Lack of Efficacy" (1.7% lorcaserin vs. 5.5% placebo). Discontinuations for adverse events (7.1% lorcaserin vs. 6.7% placebo) and other reasons were similar.
Completion rates for Year 2 were similar across the treatment groups: 74.3%, 72.7%, and 68.9% for patients continuing on lorcaserin for both years, patients taking placebo both years, and patients switching from lorcaserin to placebo in Year 2, respectively. Discontinuations for adverse events were also similar across the treatment groups.
"The positive outcome of the BLOOM trial serves as a very significant milestone for Arena, demonstrating lorcaserin's potential to provide a new treatment option for patients who need to lose weight and keep it off," stated Jack Lief, Arena's President and Chief Executive Officer. "Given lorcaserin's status as the only novel, single agent weight loss therapeutic in Phase 3 development, as well as data that continues to support our expectation for a well-tolerated and efficacious drug, I expect to have a range of commercialization options to consider."
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. Results are expected around the end of September 2009. BLOOM-DM is currently enrolling 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 and HbA1c levels 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 monitoring board.
Conference Call & Webcast
Arena will host a conference call and webcast to discuss the results today, Monday, March 30, 2009 at 8:30 a.m. Eastern Time (5:30 a.m. Pacific Time). Jack Lief, President and Chief Executive Officer, Dominic P. Behan, Ph.D., Senior Vice President and Chief Scientific Officer, William R. Shanahan, M.D., Vice President and Chief Medical Officer, and Christen M. Anderson, M.D., Ph.D., Vice President, Clinical Development, will host the conference call.
The conference call may be accessed by dialing 877.874.1565 for domestic callers and 719.325.4758 for international callers. Please specify to the operator that you would like to join the "Lorcaserin BLOOM Trial Results" conference call. The conference call will be webcast live under the investor relations section of Arena's website at www.arenapharm.com, and will be archived there for 30 days following the call. Please connect to Arena's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.
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.
A 2007 report by the US Department of Health and Human Services states that approximately one-third of US adults are obese and two-thirds have been told by a health care provider that they are overweight. Medical and related costs of obesity 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. 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® and Arena® 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 development, therapeutic indication, tolerability, safety, selectivity, efficacy and potential of lorcaserin; the significance of the review of echocardiographic data and lorcaserin's effect on the development of FDA-defined valvulopathy; the protocol, design, scope, enrollment and other aspects of the lorcaserin trials; the continued advancement of the related program; the significance of the BLOOM results; the impact of weight loss on health, including improving cardiovascular risk factors and reducing type 2 diabetes; 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 to meet the FDA's requirements for approval and the approval of lorcaserin for marketing; commercialization options and the coverage of lorcaserin patents; and about Arena's 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, the 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.
Contacts: Jack Lief Julie Normart
President and CEO WeissComm Partners
Arena Pharmaceuticals, Inc.
858.453.7200, ext. 1682