New Data From Arena Pharmaceuticals' Pivotal BLOSSOM Trial of Lorcaserin Demonstrate Improvements in Patients' Body Composition, Cardiovascular Risk Factors and Quality of Life
Late-Breaking Data Presented at the 27th Annual Scientific Meeting of The Obesity Society Expand on Previously Announced Highly Significant Top-Line Weight Loss Results -
WASHINGTON, Oct. 27, 2009 /PRNewswire-FirstCall/ -- Arena
Pharmaceuticals, Inc. (NASDAQ:ARNA) 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.
The late-breaking data were presented by Lee Kaplan, M.D.,
Ph.D., Associate Professor of Medicine at Harvard Medical School
and Director of the Massachusetts General Hospital Weight Center,
at Obesity 2009, the 27th Annual Scientific Meeting of The Obesity
Society.
"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."
William R. Shanahan, M.D., Arena's Vice President and Chief
Medical Officer, stated, "Treatment with lorcaserin offers patients
the opportunity to achieve sustainable weight loss in a
well-tolerated manner, resulting in improved cardiometabolic health
and quality of life. In order to improve overall health, it's
important to see these measurements moving in the right direction
as patients reduce their weight. Based on lorcaserin's safety and
efficacy profile, we expect primary care physicians to find
lorcaserin an attractive first-line therapy for weight
management."
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:
Body Composition
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.
Cardiovascular Risk Factors
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).
Quality of Life
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%).
Quality of Life, as assessed by the Impact of Weight on Quality
of Life-Lite (IWQOL-Lite) questionnaire, improved to a
significantly greater extent in the lorcaserin twice daily
(p<0.0001) and lorcaserin once daily (p<0.01) groups as
compared to placebo at Week 52. All measurements, including
physical function, self esteem, sexual life, public distress and
work, improved in a dose-dependent fashion.
"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."
Safety and Tolerability Profile
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%.
Cardiovascular Safety
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.
New data demonstrate that similar numbers of mitral
insufficiency and aortic insufficiency shifts were reported for
patients on lorcaserin and placebo. In patients with pre-existing
FDA-defined valvulopathy at baseline, changes in valvular
regurgitant scores did not differ between the placebo and
lorcaserin groups. The majority of patients experienced either no
change or an improvement in valvular regurgitation.
Previously Announced Efficacy Data
The previously announced BLOSSOM data demonstrated that
lorcaserin was highly efficacious, achieving statistical
significance on all three co-primary efficacy endpoints, and was
very well tolerated. Lorcaserin patients achieved highly
significant categorical and absolute weight loss over 52 weeks of
treatment. About two-thirds (63.2%) of lorcaserin patients dosed
twice daily who completed the trial according to the protocol lost
at least 5% of their weight, compared to 34.9% of patients on
placebo, and more than one-third (35.1%) of these lorcaserin
patients lost at least 10% of their weight, compared to 16.1% for
placebo. The average weight loss for lorcaserin patients dosed
twice daily was 17.0 pounds, compared to 8.7 pounds for placebo.
The top quartile of lorcaserin patients who completed the trial
according to protocol and had their Week 52 weight recorded lost an
average of 35.1 pounds.
Patient Disposition
BLOSSOM evaluated 4,008 patients with an average BMI of 35.9 and
baseline weight of 220 pounds. The Week 52 completion rate was
higher for patients on lorcaserin 10 mg twice daily (57.2%) and 10
mg once daily (59.0%) compared to patients on placebo (52.0%).
Discontinuations for adverse events were low and as follows:
lorcaserin 10 mg twice daily (7.2%), 10 mg once daily (6.2%) and
placebo (4.6%).
BLOSSOM Trial Design
BLOSSOM is a double-blind, randomized, placebo-controlled trial
in approximately 100 sites in the US. The trial evaluated 10 mg of
lorcaserin dosed once or twice daily versus placebo over a one-year
treatment period in obese patients (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 dose titration or a run-in period. Patients were randomized
at baseline in a 2:2:1 ratio to lorcaserin 10 mg twice daily,
placebo or lorcaserin 10 mg once daily. Patients received
echocardiograms at baseline, month 6 and at the end of the trial to
assess heart valve function over time. In contrast to the BLOOM
trial, there were no echocardiographic exclusion criteria for entry
into BLOSSOM and there was no oversight or interim data review
monitoring by an independent safety monitoring board.
Phase 3 Program Overview
The lorcaserin Phase 3 program consists of three trials: BLOOM,
BLOSSOM and BLOOM-DM (Behavioral modification and Lorcaserin for
Overweight and Obesity Management in Diabetes Mellitus). Enrollment
in the lorcaserin Phase 3 program is complete with approximately
7,800 patients. Positive results from BLOOM were presented at the
69th Scientific Sessions of the American Diabetes Association in
June 2009. BLOOM and BLOSSOM comprise the Phase 3 pivotal
registration program and will be the basis for the lorcaserin NDA
submission. BLOOM-DM, which is planned as a supplement to the NDA,
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.
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.
About Lorcaserin
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.
About Weight Management
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.
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 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.
Arena Pharmaceuticals® and Arena® are registered service
marks of the company. "APD" is an abbreviation for Arena
Pharmaceuticals Development.
Forward-Looking Statements
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, advancement, therapeutic indication and use,
tolerability, safety, selectivity, efficacy, and regulatory
approval of lorcaserin; the protocol, design, scope, enrollment and
other aspects of the lorcaserin trials; lorcaserin's commercial and
other potential, including in managing weight, meeting patients'
and physicians' needs, changing treatment, improving health and
quality of life and generating interest; significance of the
lorcaserin trial results and the completion of the lorcaserin Phase
3 pivotal registration program; the FDA's approval process and
requirements; the risk of developing valvulopathy; the potential of
the lorcaserin Phase 3 program and its results to satisfy the FDA's
approval requirements; future activities, results and announcements
relating to lorcaserin, including submitting an NDA for lorcaserin,
submitting the BLOOM-DM results as a supplement to the NDA, and
commercializing lorcaserin; the impact of weight loss on health;
lorcaserin's patent coverage; and 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, 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 or commercialize 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
additional funds; 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.
Contact: Arena Pharmaceuticals, Inc. Media Contact: Russo Partners Jack Lief David Schull, President President and CEO david.schull@russopartnersllc.com 858.717.2310 Cindy McGee Manager, IR and Corporate Anthony J. Russo, Ph.D., CEO Communications tony.russo@russopartnersllc.com cmcgee@arenapharm.com 212.845.4251 858.967.1646
Source: Arena Pharmaceuticals, Inc.
CONTACT: Jack Lief, President and CEO, Cindy McGee, Manager, IR
and
Corporate Communications, +1-858-967-1646, cmcgee@arenapharm.com, both
of
Arena Pharmaceuticals, Inc.; Media, David Schull, President,
+1-858-717-2310,
david.schull@russopartnersllc.com,
or Anthony J. Russo, Ph.D., CEO,
+1-212-845-4251, tony.russo@russopartnersllc.com,
both of Russo Partners
Web Site: http://www.arenapharm.com/
Posted: October 2009
