2Belviq® - lorcaserin Clinical Application Indications:Chronic weight management in:Adults with BMI ≥ 30kg/m2 or BMI ≥ 27kg/m2 and at least one weight related condition (HTN, HLD, T2DM)Place in therapy:As adjunct to diet and exercise for chronic weight management
6Belviq® - lorcaserin Drug Facts Pharmacology:The exact mechanisms is not known.Belviq® is believed to decrease food consumption and promote satiety by selectively activating 5-HT2C receptors on anorexigenic proopiomelanocortin neurons located in the hypothalamus.
7Belviq® - lorcaserin Drug Facts Pharmacokinetics:ABioavailability: Not been determinedCmax: hoursDLoracersin distributes to the CSF and CNS in humans. Moderately bound (~70%) to human plasma proteins.MExtensively hepatic, producing two major inactive metabolites as well as minor metabolites.EUrine (92%, as metabolites), feces (2%, as metabolites).Half-life of ~ 11hrs, SS reached within 3 days after BID dosing, and accumulation is estimated to be approximately 70%.
8Belviq® - lorcaserin Drug Interactions Drug Interactions – Object Drugs: serotonergic effect of other serotonergic agents or agents that impair serotonin metabolism effect of CYP2D6 substratesInhibits CYP2D6 metabolism
9Belviq® - lorcaserin Drug Interactions Drug Interactions – Precipitant Drugs:None given in the package insert.
10Belviq® - lorcaserin Adverse Effects Common Adverse Effects:LorcaserinPlaceboHeadache16.8%10.1%Dizziness8.5%3.8%Nausea8.3%5.3%Fatigue7.2%3.6%Diarrhea6.5%5.6%Constipation5.8%3.9%
11Belviq® - lorcaserin Monitoring Parameters Efficacy Monitoring:Loss of at least 5% of baseline body weight by week 12Toxicity Monitoring:S/sx of serotonin syndromeS/sx of valvulopathySerotonin syndrome s/sx = Mental status changes, tachycardia, labile blood pressure, hyperthermia, N/V/DValvulopathy s/sx = Dyspnea, dependent edema, CHF, new heart murmur
12Belviq® - lorcaserin Prescription Information Dosing:10mg po twice dailyCost:AWP $240 (60ct)Net Invoice Cost $202Cardinal Health (12/21/14)
13Belviq® - lorcaserin Literature Review Purpose: To evaluate the safety and efficacy of lorcaserin for weight loss and maintenance of weight loss when administered with a lifestyle modification planDesign: Randomized, placebo- controlled, double-blind clinical trialSmith SR, et al., NEJM Jul 15;363(3):
14Belviq® - lorcaserin Literature Review Inclusion ExclusionInclusionExclusion18 to 65 years oldModerate or more severe mitral regurgitation or mild or more severe aortic regurgitationBMI of 30 to 45 orBMI of 27 to 45 with at least 1 coexisting condition (HTN,HLD, CVD, impaired glucose tolerance, sleep apnea)Depression or other major psychiatric disease within 2 years before randomization that necessitated treatment with prescription medicationDiabetesSBP > 140mmHg or DBP > 90Pregnancy or lactationSmith SR, et al., NEJM Jul 15;363(3):
15Belviq® - lorcaserin Literature Review Baseline Characteristics:CharacteristicLorcaserin (n=1595)Placebo (n=1587)White1081 (67.9)1046 (66.0)Female1321 (82.9)1331 (84.0)Age43.8 ± 0.344.4 ± 0.3Weight in kg100.4 ± 0.499.7 ± 0.4BMI36.2 ± 0.1Waist Circum. (cm)109.6 ± 0.3109.2 ± 0.3100.4 kg ~ 220 pounds109.6 cm ~ 43 inchesSmith SR, et al., NEJM Jul 15;363(3):
16Belviq® - lorcaserin Literature Review Treatment Arms:Lorcaserin or placebo twice daily (1:1) x52 weeksLorcaserin or placebo x52 weeksPlacebo → PlaceboLorcaserin → lorcaserin or placebo (2:1)Efficacy: Weight lossSmith SR, et al., NEJM Jul 15;363(3):
17Belviq® - lorcaserin Literature Review Statistical Analysis:Echocardiographic safety end point was primary determinant of sample size1879 patients (940 in each group) required for 80% power at the 5% level of significance3182 patients recruitedModified ITT population (screening Echo and at least one post-baseline Echo) analyzedEchocardiographic safety end point = proportion of patients in whom FDA-defined valvulopathy had developed by week 52Proportion of patients in placebo group in whom FDA-defined valvulopathy would develop was estimated at approximately 5% per yearA noninferiority margin of −0.025 (equivalent to a relative risk of valvulopathy with lorcaserin of 1.5) was also used in the estimation of sample sizeSmith SR, et al., NEJM Jul 15;363(3):
18Belviq® - lorcaserin Literature Review Primary Endpoint:Weight loss at 1 yearMaintenance of weight loss at 2 yearsSecondary Endpoint:Waist circumference, BP, cholesterol, fasting insulin and glucose, CRP, fibrinogen, impact of weight on QOLEchocardiographySmith SR, et al., NEJM Jul 15;363(3):
19Belviq® - lorcaserin Literature Review Results: ITT PopulationEnd PointLorcaserin(n=1538)Placebo(n=1499)P-valueLoss of ≥5% of body weightPatients (%)47.520.3<0.001Weight change (kg)-5.82 ± 0.2-2.2 ± 0.1Loss of ≥10% of body weight (%)22.67.7Waist circumference (cm)-6.8 ± 0.2-3.9 ± 0.2BMI-2.09 ± 0.06-0.78 ± 0.055.82kg = 12.8 pounds2.2 kg = 4.84 poundsWaist circumference 6.8 cm = 2.7 inchesSmith SR, et al., NEJM Jul 15;363(3):
21Belviq® - lorcaserin Literature Review Discussion:At year 1, 47.5% of lorcaserin group vs 20.3% of placebo had lost 5% or more of body weightLoss was maintained in more patients who continued to receive lorcaserin in year 2 (67.9%) vs placebo (50.3%)Rate of valvulopathy was NOT increased with use of lorcaserinSmith SR, et al., NEJM Jul 15;363(3):
22Belviq® - lorcaserin Literature Review ProsConsNew agent for weight management as adjunct to reduced-calorie diet and exercise.Patients may have regained their weight after trial withdrawal (ITT population with LOCF)Over 50% of lorcaserin patients achieved goal5% of body weight amounted to approximately 12 poundsWeight loss of 5% to 10% can have beneficial effectsAssumed valvulopathy would develop in 5% of placebo within 1 year (only 2.3% found) – underpoweredIncreased valvulopathy and psychiatric issues not observedRate of discontinuation was nearly 50%Applicability (white, females, healthy)Trial also had neither a placebo run-in period nor a dose adjustment periodSmith SR, et al., NEJM Jul 15;363(3):
23Belviq® - lorcaserin Summary Belviq®, lorcaserin, is indicated for weight management in adults (BMI≥30 or BMI≥ RF) as an adjunct to diet and exercisePotentially increases effects of other serotonergic agents and may increase substrates metabolized by CYP2D6Dosed 10mg po BIDADE include headache, dizziness, & fatigueLong-term data is lackingBelviq® was required to submit additional data as the agent was reported to be associated with tumor risk in rodents (mammary adenocarcinomas)
24Belviq® - lorcaserin References Accessed 09/14/14.Belviq® Package Insert. Arena Pharmaceuticals. June 2012.Smith SR, et al., Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med Jul 15;363(3):