1. Manufacturer: Arena Pharmaceuticals FDA Approval Date: 06/27/2012
Belviq® - lorcaserin
Manufacturer:
Arena Pharmaceuticals
FDA Approval Date: 06/27/2012

2. Belviq® - 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

3. Belviq® - lorcaserin Clinical Application
Contraindications:
Pregnancy
Warnings:
Serotonin syndrome
Valvular heart disease
Psychiatric disorders or cognitive impairment

4. Belviq® - lorcaserin Clinical Application
Precautions:
Hypoglycemia in diabetics
Priapism
Heart rate decreases
Pulmonary hypertension

5. Belviq® - lorcaserin Clinical Application
Pregnancy:
Category X
Lactation:
Not recommended.
Belviq® may increase prolactin.

6. Belviq® - 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.

7. Belviq® - lorcaserin Drug Facts
Pharmacokinetics: A
Bioavailability: Not been determined
Cmax: hours D
Loracersin distributes to the CSF and CNS in humans. Moderately bound (~70%) to human plasma proteins. M
Extensively hepatic, producing two major inactive metabolites as well as minor metabolites. E
Urine (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%.

8. Belviq® - lorcaserin Drug Interactions
Drug Interactions – Object Drugs:
 serotonergic effect of other serotonergic agents or agents that impair serotonin metabolism
 effect of CYP2D6 substrates
Inhibits CYP2D6 metabolism

9. Belviq® - lorcaserin Drug Interactions
Drug Interactions – Precipitant Drugs:
None given in the package insert.

10. Belviq® - lorcaserin Adverse Effects
Common Adverse Effects:
Lorcaserin
Placebo
Headache
16.8%
10.1%
Dizziness
8.5%
3.8%
Nausea
8.3%
5.3%
Fatigue
7.2%
3.6%
Diarrhea
6.5%
5.6%
Constipation
5.8%
3.9%

11. Belviq® - lorcaserin Monitoring Parameters
Efficacy Monitoring:
Loss of at least 5% of baseline body weight by week 12
Toxicity Monitoring:
S/sx of serotonin syndrome
S/sx of valvulopathy
Serotonin syndrome s/sx = Mental status changes, tachycardia, labile blood pressure, hyperthermia, N/V/D
Valvulopathy s/sx = Dyspnea, dependent edema, CHF, new heart murmur

12. Belviq® - lorcaserin Prescription Information
Dosing:
10mg po twice daily
Cost:
AWP $240 (60ct)
Net Invoice Cost $202
Cardinal Health (12/21/14)

13. Belviq® - 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 plan
Design: Randomized, placebo- controlled, double-blind clinical trial
Smith SR, et al., NEJM Jul 15;363(3):

14. Belviq® - lorcaserin Literature Review
Inclusion Exclusion
Inclusion
Exclusion
18 to 65 years old
Moderate or more severe mitral regurgitation or mild or more severe aortic regurgitation
BMI of 30 to 45 or
BMI 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 medication
Diabetes
SBP > 140mmHg or DBP > 90
Pregnancy or lactation
Smith SR, et al., NEJM Jul 15;363(3):

15. Belviq® - lorcaserin Literature Review
Baseline Characteristics:
Characteristic
Lorcaserin (n=1595)
Placebo (n=1587)
White
1081 (67.9)
1046 (66.0)
Female
1321 (82.9)
1331 (84.0)
Age
43.8 ± 0.3
44.4 ± 0.3
Weight in kg
100.4 ± 0.4
99.7 ± 0.4
BMI
36.2 ± 0.1
Waist Circum. (cm)
109.6 ± 0.3
109.2 ± 0.3
100.4 kg ~ 220 pounds
109.6 cm ~ 43 inches
Smith SR, et al., NEJM Jul 15;363(3):

16. Belviq® - lorcaserin Literature Review
Treatment Arms:
Lorcaserin or placebo twice daily (1:1) x52 weeks
Lorcaserin or placebo x52 weeks
Placebo → Placebo
Lorcaserin → lorcaserin or placebo (2:1)
Efficacy: Weight loss
Smith SR, et al., NEJM Jul 15;363(3):

17. Belviq® - lorcaserin Literature Review
Statistical Analysis:
Echocardiographic safety end point was primary determinant of sample size
1879 patients (940 in each group) required for 80% power at the 5% level of significance
3182 patients recruited
Modified ITT population (screening Echo and at least one post-baseline Echo) analyzed
Echocardiographic safety end point = proportion of patients in whom FDA-defined valvulopathy had developed by week 52
Proportion of patients in placebo group in whom FDA-defined valvulopathy would develop was estimated at approximately 5% per year
A 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 size
Smith SR, et al., NEJM Jul 15;363(3):

18. Belviq® - lorcaserin Literature Review
Primary Endpoint:
Weight loss at 1 year
Maintenance of weight loss at 2 years
Secondary Endpoint:
Waist circumference, BP, cholesterol, fasting insulin and glucose, CRP, fibrinogen, impact of weight on QOL
Echocardiography
Smith SR, et al., NEJM Jul 15;363(3):

19. Belviq® - lorcaserin Literature Review
Results: ITT Population
End Point
Lorcaserin
(n=1538)
Placebo
(n=1499)
P-value
Loss of ≥5% of body weight
Patients (%)
47.5
20.3
<0.001
Weight change (kg)
-5.82 ± 0.2
-2.2 ± 0.1
Loss of ≥10% of body weight (%)
22.6
7.7
Waist circumference (cm)
-6.8 ± 0.2
-3.9 ± 0.2
BMI
-2.09 ± 0.06
-0.78 ± 0.05
5.82kg = 12.8 pounds
2.2 kg = 4.84 pounds
Waist circumference 6.8 cm = 2.7 inches
Smith SR, et al., NEJM Jul 15;363(3):

20. Belviq® - lorcaserin Literature Review
Selected Adverse Events: n, (%)
Event
Lorcaserin (n=1593)
Placebo (n=1584)
Headache
287 (18.0)
175 (11.0)
Dizziness
130 (8.2)
60 (3.8)
Nausea
119 (7.5)
85 (5.4)
Diarrhea
109 (6.8)
Fatigue
95 (6.0)
48 (3.0)
Dry mouth
83 (5.2)
37 (2.3)
Vomiting
59 (3.7)
42 (2.7)
Insomnia
41 (2.6)
58 (3.7)
Smith SR, et al., NEJM Jul 15;363(3):

21. Belviq® - lorcaserin Literature Review
Discussion:
At year 1, 47.5% of lorcaserin group vs 20.3% of placebo had lost 5% or more of body weight
Loss 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 lorcaserin
Smith SR, et al., NEJM Jul 15;363(3):

22. Belviq® - lorcaserin Literature Review
Pros
Cons
New 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 goal
5% of body weight amounted to approximately 12 pounds
Weight loss of 5% to 10% can have beneficial effects
Assumed valvulopathy would develop in 5% of placebo within 1 year (only 2.3% found) – underpowered
Increased valvulopathy and psychiatric issues not observed
Rate of discontinuation was nearly 50%
Applicability (white, females, healthy)
Trial also had neither a placebo run-in period nor a dose adjustment period
Smith SR, et al., NEJM Jul 15;363(3):

23. Belviq® - lorcaserin Summary
Belviq®, lorcaserin, is indicated for weight management in adults (BMI≥30 or BMI≥ RF) as an adjunct to diet and exercise
Potentially increases effects of other serotonergic agents and may increase substrates metabolized by CYP2D6
Dosed 10mg po BID
ADE include headache, dizziness, & fatigue
Long-term data is lacking
Belviq® was required to submit additional data as the agent was reported to be associated with tumor risk in rodents (mammary adenocarcinomas)

24. Belviq® - 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):