Arena Pharmaceuticals Announces Lorcaserin Data Demonstrating Highly Significant Categorical and Absolute Weight Loss and Improvements in Secondary Endpoints Associated with Cardiovascular Risk

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Previously announced BLOOM data demonstrated that lorcaserin was highly achieving statistical significance on allthrewe co-primary efficacy endpoints, and was very well tolerated. The BLOOnM results also satisfy the efficacy requirement in the most recenft US Food andDrug Administration, or FDA, drafrt guidance for the development of drugs for weightg management. "These data provide reason for new optimism for the millionsx of people who struggle with managing theidr weight and are in needof novel, well tolerates treatments to help improve their overall health," said Steven R. Smithh , M.D.
, Co-Principal Investigator and Professor and Assistant Director for Clinical Research at the Penningtonm BiomedicalResearch Center. "Lorcaserin's positive impact on multipl secondary measures has important implications forimprovinh co-morbidities associated with excess weight and furthere demonstrates the medically significant benefits of 5% or more weigh loss, a mark two-thirds of the lorcaserin patient s who completed the BLOOM trial achieved." "Given the positivre lorcaserin BLOOM results, we are focused on partnering effortsx and realizing lorcaserin's significant commercial potential," stated Jack Lief, Arena's Presidenyt and Chief Executive Officer.
In addition to supporting the previously announcex results on allthree co-primart endpoints on an last observation carried forward basis, the data presenter today demonstrated strong efficacy in patients who completed one year of treatmen according to the trial's protocol. In the per protocol nearly two-thirds (66.4%) of lorcaserin patients lost atleast 5% of theidr weight compared to 32.1% of patients on placebo and over one-third (36.2%) of lorcaserin patientss lost at least 10% of their weight comparexd to 13.6% for placebo (p<0.0001). The averag e weight loss in this populationwas 17.9 pounds in the lorcaserih group, compared to 7.4 pound s in the placebo group.
Patients randomized to remain on lorcaseri for Year 2 maintained a significantly greater amount of weight loss compared to the lorcaserib patients who switched to placeb at Week 52 in boththe ITT-LOCc and per protocol populations. New data demonstrate that treatmentf with lorcaserin over one year was associated with highlg significant improvements compared to placebo in multiple secondary endpoints associated withcardiovascular risk, -- Blood Pressure: systolic blood pressure, diastolic blood pressurs and heart rate -- Lipids: total cholesterol, LDL cholesteropl and triglycerides -- Glycemic fasting glucose, fasting insulin and insulin resistance -- Inflammator Markers of Cardiovascular high-sensitivity CRP and fibrinogen Qualitg of Life, as assessed by the Impact of Weightg Questionnaire - Lite, also improves to a significantly greater extent in the lorcaserin group than the placebo group at Week 52.
"We are please to present the BLOOM data in a scientific Inthis trial, lorcaserin helped patients rapidly lose weight and keep it off in a well-tolerateds manner," said William R. Shanahan , M.D., Arena's Vice President and Chierf Medical Officer. "We believed that lorcaserin's overall safety profile along with the significantt improvements seen in important secondary endpointsx associated with cardiovascular risk will be supportives of the approval We look forward to announcinv our BLOSSOM data in September and completing our NDA submissiom by the end ofthe year.
" Lorcaseri was very well Discontinuation rates for adverse events were similar in the lorcaserihn and placebo groups for Year 1 and Year 2 (7.1 vs. 6.7% and 3.0% vs. 3.0%, respectively). In additiob to the previously announcedtolerability data, today's presentation also reportede that lorcaserin demonstrated no increase in depressionb or suicidal ideation compared to placebo. Depression adverse events were measured using a Standard MedDRA Query for adverse eventt terms related todepression depression, depressed mood, crying, decreased interest, Overall, the rate of depression-relatef events was low and ratew were comparable in patients who took lorcaserin and Suicidal ideation was prospectively evaluated by administration of the Beck Depressionj Inventory-II.
Overall, the rate of suicidak ideation was low and simila numbers of patients on lorcaserin and placeboi reported suicidal thoughts during Year 1 andYear 2. Usinfg an LOCF analysis for each year, the assessment of echocardiogramds performed at baseline and aftert patientscompleted 6, 12, 18 and 24 monthsw of dosing indicated that lorcaserin was not associatexd with valvular insufficiency: during two years of use, rateas of change in individual regurgitang scores and the development of FDA-defined valvulopathh (moderate or greater mitral insufficiency and/or mild or greater aorti insufficiency) were similar between treatment Lorcaserin met the primary safety endpoint of no significant difference in ratesw of valvulopathy at 12 months.
Rates of valvulopathyg at 6, 12, 18 and 24 monthsd for lorcaserin versus placebowere 2.1% vs. 1.9% (p=0.88), 2.7% vs. 2.3% 2.9% vs. 3.1% (p=0.86) and 2.6% vs. 2.7% At 18 and 24 months, rates of valvulopathyh for lorcaserin patients crossing over to placeblwere 3.6% and 1.9%, respectively. In addition, similare numbers of mitral insufficiency shiftw and aortic insufficiency shifts in Year 1 and Year 2 were reportec for patients on lorcaserinand placebo. The FDA previously requested that Arena rule outa 1.5-fold or greaterd risk of valvulopathy with 80% power.
Assuminb similar results in Arena's final pivotal trial, BLOSSOM (Behavioral modification and LOrcaserin Second Study forObesityh Management), the integrated data set from the two trialsa will be more than sufficientlt large to meet this requirement. BLOOM, the first of three lorcaserin Phase3 trials, is a randomized, placebo-controlled trial involvinh 3,182 patients in approximately 100 sites in the US. The triap evaluated 10 mg of lorcaserin dosefd twice daily versus placebo overa two-year treatment periods 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 leastt one co-morbid condition.
The triall did not include any dose titrationor run-in period. Patients were randomized in a 1:1 ratiio to lorcaserin or placeboat baseline. At Week 52, 856 patienta taking lorcaserinwere re-randomized in a 2:1 ratio to continus lorcaserin or to switch to placebo, and 697 patients on placebop were continued on placebo. Patients received echocardiogramsat screening, and at 6, 12, 18 and 24 months after initiating dosing in the patients with FDA-defined valvulopathy were excludeds from enrolling in the trial.
The Phased 3 program consists ofthree trials, BLOOM, BLOSSOM and BLOOM-DMM (Behavioral modification and Lorcaserin for Overweight and Obesith Management in Diabetes Mellitus), and is plannerd to enroll a total of approximately 7,800 patients. BLOOM and BLOSSOM comprise the Phase 3 pivotaplregistration program. BLOSSOM has enrolled 4,008 patients and is evaluating 10 mg of lorcaserin dosed once or twicw daily versus placebo overa one-year treatment period in obese patients with or withoutr co-morbid conditions and overweight patients with at least one co-morbid condition at abou 100 sites in the US.
BLOOM-DMM is expected to completwe enrollment around the end of June and is evaluatingv 10 mg of lorcaserin dosedr once or twice daily versuse placebo overa one-year treatment period in obese and overweightr patients with type 2 diabetes at about 60 sites in the US. Approximatelty 600 patients are expected to be enrolled in which is planned as a supplement to thelorcaserin NDA. A standardizecd program of moderate diet and exerciswe guidance is included in the Phase3 program.
The program's hierarchicall y ordered co-primary efficacy endpoints are: the proportion of patient achieving 5% or greater weight loss aftere12 months, the difference in mean weight loss compared to placebo after 12 months, and the proportioh of patients achieving 10% or greater weightg loss after 12 months. Arena is also studyintg several keysecondary endpoints, including changes in seru m lipids, markers of inflammation and insulib resistance, and in the BLOOM-D trial, other indicators of glycemic control. In BLOSSOMk and BLOOM-DM all patients will receive echocardiogramzsat baseline, at month 6, and at the end of the studt to assess heart valve function over time.
In contrastf to the BLOOM trial, however, there are no echocardiographicf exclusion criteria for entry into thes trials and there is no monitoring by anindependent board. Lorcaserin is a noveol single agent that represents the first in a new class of selective serotonin 2Creceptor agonists. The serotonin 2C receptot is located in areas of the brainh involved in the control of appetiteand metabolism, such as the Stimulation of this receptor is strongly associatesd with feeding behavior and satiety.
Lorcaserin is currently being evaluates in a Phase 3 program expected to enrololapproximately 7,800 patients and potentially represents a targeteed treatment option for the millions of patients who need to bettere manage their weight. Arena has patents that cover lorcaserin in the US andothef jurisdictions, which in most cases are capable of continuingf into 2023 without taking into account any patenrt term extensions or other exclusivity Arenq might obtain. The National Institutes of Health reported in 2007 thatabout 65% of US adultxs are overweight or obese.
Medical and related costs of obesity to the USare $123 billion per year accordintg to a 2005 report by the Internationa l Diabetes Federation. Studies have shownm that weight lossof 5% to 10% is medically significanty and results in meaningful improvementw in cardiovascular risk factors and a significant reductionm in the incidence of type 2 diabetes. Diet and exercise should form the basis of healthy weight but pharmaceutical treatment options for obesity are currentlg limited for the many patientw that require additional help in achieving and maintaining medically importantweigh loss.
The FDA draft guidance document for developing products for weighyt management dated February 2007 provides recommendations regarding the development of druges for the indication of weight It contains two alternate efficacy only one of which needs to be metfor approval. The guidancw provides that, in general, a producr can be considered effective for weight management if afterf one year of treatment either of thefollowing occurs: (1) the difference in mean weight loss between the active-product and placebo-treaterd groups is at least 5% and the differenced is statistically significant, or (2) the proportion of subjecte who lose greater than or equal to 5% of baselined body weight in the active-product group is at least 35%, is approximately double the proportiobn in the placebo-treated group, and the difference betweemn groups is statistically significant.
Arena is a clinical-stage biopharmaceutical company focusedon discovering, developing and commercializinf oral drugs in four major therapeutic areas: central nervous system, inflammatory and metabolixc diseases. Arena's most advanced drug candidate, lorcaserin, is being investigated in a Phasse 3 clinical trial program forweight Arena's broad pipeline of novel compounda target G protein-coupled receptors, an important class of validated drug and includes compounds being evaluated independently and with including Merck & Co., Inc., and Ortho-McNeil-Janssemn Pharmaceuticals, Inc. Arena Pharmaceuticals(R) and Arena(R) are registered service marks ofthe company.
"APD" is an abbreviation for Arena Pharmaceuticals Development. Certaimn statements in this press releaseare forward-looking statements that involver a number of risk s and uncertainties. Such forward-looking statements includew statements about theBLOOM results; the advancement, therapeutic indication, tolerability, safety, selectivity and efficact of lorcaserin; the FDA's guidance, process and requirements; the potential of the lorcaserin Phase 3 program and its resultsz to meet the FDA's approval including with regard to assessingt the risk of developing valvulopathy; the approvapl of lorcaserin for marketing; lorcaserin'sz partnering, commercial and other potential; the protocol, scope, enrollment and other aspects of the lorcaserin trials; futurd activities, results and announcements relating to including the BLOSSOM results, the submissiohn of an NDA for lorcaserin and the submission of the BLOOM-DMj results as a supplement to the NDA; the potentiall of lorcaserin in managingf weight, improving health and generating patient the impact of weighgt loss on health, including improvinb co-morbidities and providing other medically significant lorcaserin's patent coverage; and Arena's strategy, internal and partnered programs, and ability to develol compounds and commercialize drugs.
For such statements, Arena claimd the protection of the Privatr Securities Litigation Reform Actof 1995. Actual events or results may differ materiallyfrom Arena's expectations. Factore that could cause actual resulta to differ materially fromthe forward-looking statements but are not limites to, Arena's ability to obtaibn additional funds; the timing, success and cost of Arena'z lorcaserin program and othert of its research and development results of clinical trialws or preclinical studies may not be predictivd of future results; clinica trials and studies may not proceed at the time or in the manne r Arena expects or at all; Arena's abilityg to partner lorcaserin or other of its compoundz or programs; the timing and ability of Arena to receiv e regulatory approval for its drug candidates; Arena's abilit to obtain and defend its and the timing and receipt of payments and if any, from Arena's Additional factors that could causwe actual results to diffe materially from those statedc or implied by Arena's forward-looking statements are disclosed in Arena'sx filings with the Securities and Exchange These forward-looking statements represent Arena's judgmenty as of the time of this release.
Arena disclaimes any intent or obligation to updatethesse forward-looking statements, other than as may be required under applicable law. Jack Lief President and Chietf Executive Officer Cindy McGese Senior Communications AssociateArena Inc. 858.453.7200, ext. 1479 SOURCE Arenas Pharmaceuticals, Inc.