1. on behalf of the CAMELLIA-TIMI 61 Investigators
Lorcaserin Improves Renal Outcomes in Obese and Overweight Patients in the CAMELLIA-TIMI 61 Trial
E.A. Bohula, S.D. Wiviott, J.P. Dwyer, S.E. Inzucchi, D.K. McGuire, K. Im, S.A. Murphy, W. Miao, C. Perdomo, T. Patel, S.R. Smith, A.C. Keech, M.S. Sabatine, & B.M. Scirica
on behalf of the CAMELLIA-TIMI 61 Investigators

2. Background
Obesity is associated with an increased risk of developing kidney disease
Unclear if mechanism is causal or via associated comorbidities
Lifestyle modification & bariatric surgery improves albuminuria, but has mixed effects on eGFR
Renal effects of pharmacologically-mediated weight loss not well described

3. Lorcaserin Selective agonist of serotonin (5HT)-2C receptor
Hypothalamic activation of the POMC (pro-opiomelanocortin) pathway → appetite suppression
Based on phase 3 studies testing weight loss efficacy, approved for use in the US for chronic weight management +
5HT2CR
Lorcaserin
Image modified from Marx J. Science. 2003;299:

4. Trial Schema Lorcaserin PLACEBO 10mg BID N = 12,000
Obese or Overweight (BMI≥27kg/m2)
Established CV disease* or
T2DM & other CV risk factors†
N = 12,000
Median Follow up:
3.3 yrs
Exercise & Reduced-Calorie Diet
Lorcaserin
10mg BID
PLACEBO
RANDOMIZE 1:1 DOUBLE BLIND
Stratified by CV disease or CV RF
Follow up visits Q 3mo x 2yr then Q 4mo
Primary CV Safety EP: MACE (CV death, MI, CVA) Primary Metabolic Efficacy EP: Incident T2DM in pts with pre-DM
*CAD, PAD or cerebrovascular disease; †T2DM with ≥1 of following: HTN, HL, hsCRP>3, eGFR 30-60, albuminuria
Bohula EA et al. Am Heart J 2018;202:39-48

5. Primary Trial Outcomes
N = 12,000
N = 3,991
CV Death, MI, Stroke
(CV Safety)
Incident Diabetes
(Metabolic Efficacy)
10.3% (204 events)
Lorc
n (%/yr)
Pbo
MACE HR (95%CI)
CV death, MI, or stroke
364
(2.0)
369
(2.1)
0.99*
(0.85, 1.14)
HR 0.81 (0.66, 0.99)
P=0.038
8.5% (172 events)
0.8
1.0
1.4
Hazard Ratio (95% CI)
Favors Lorcaserin
Favors Placebo
*P (non-inferiority) < 0.001
*Non-inferiority boundary: HR 97.5% upper bound of 1.4
Lorcaserin
Placebo
Bohula EA et al. NEJM ;379:
; Bohula EA et al. Lancet. 2018;epub

6. Renal Outcomes Pre-specified Primary Renal Composite Outcome
Persistent new or worsening micro- or macro-albuminuria*
Micro- (UACR ≥ 30mg/g) or macro-albuminuria (≥ 300mg/g)
Persistent new or worsening CKD*
Increase in CKD stage by KDIGO staging
Persistent doubling of serum creatinine*
End-stage renal disease (ESRD) = dialysis or eGFR<15
Renal transplant
Renal death
Other Pre-specified Renal Endpoints
Persistent eGFR decline by ≥ 30% or ≥ 40%*
KDIGO CKD Stage
Stage
eGFR
UACR
≥60
None 1
≥90
≥30 2
60-89 3
30-59 4
15-29 5
<15 or dialysis
eGFR by CKD-EPI (ml/min/1.73m2);
UACR by spot urinary albumin to
creatinine ratio(mg/g)
*On ≥2 consecutive measurements ≥30 days apart

7. Baseline Characteristics
Characteristic (N=12,000)
Value
Age (median, IQR)
64 [58, 69]
Male 64
Weight in kg (median, IQR)
102 [90, 116]
BMI in kg/m2 (median, IQR)
35 [32, 39]
Established CV Disease / Multiple CV RF
75 / 25
Hypertension 90
DM / Pre-DM / No DM
57 / 33 / 10
eGFR in ml/min/1.73m2 (median, IQR)
76 [63-89]
>=90 24
60-<90 57
<60 19
UACR in mg/g (median, IQR)
7.0 [ ]
<30 82
30-<300 (microalbuminuria) 15
>=300 (macroalbuminuria)
3.2
% unless otherwise specified.
Pooled data; no differences between treatment arms (p≥0.05)

8. Weight, BP & HbA1c Lorcaserin Placebo eGFR <60 (N=2357)
Δ -2.2kg
p<0.001
Δ -2.9kg
p<0.001
Δ -3.2kg
p<0.001
Δ at 1 Yr
eGFR <60
eGFR 60-<90
eGFR ≥90
Weight (kg)
-3.2†
-2.9†
-2.2† 
Δ at 1 Yr
eGFR <60
eGFR 60-<90
eGFR ≥90
Weight (kg)
-3.2†
-2.9†
-2.2† 
HbA1c (%)
-0.2†
SBP (mm Hg)
-1.1†
-1.1
†p<0.05

9. Primary Renal Composite
HR 0.84
95% CI 0.75, 0.93
P=0.001
Primary renal composite:
New or worsening albuminuria*
New or worsening CKD*
Doubling of serum Cr*
ESRD
Renal transplant
Renal death
HR 0.83
95% CI 0.73, 0.93
P=0.002
HR 0.86
95% CI 0.74, 1.01
P=0.061
*≥2 consecutive assessments ≥ 30 days apart
Overall
Lorcaserin 4.2% per year
Placebo % per year
HR 0.87 (0.79, 0.96), P=0.006

10. Renal PEP by Subgroups

11. Individual Components
Outcome
Lorcaserin
N=6000
%/Yr
Placebo
HR (95%CI)
p-value
Primary Renal Composite
4.2
4.9
0.87 (0.79, 0.96)
0.0064
Persistent new or worsening albuminuria*
2.7
3.1
0.86 (0.76, 0.97)
0.017
Persistent new or worsening CKD*
2.4
2.9
0.81 (0.72, 0.93)
0.0018
Persistent doubling of creatinine*
0.03
0.04
0.75 (0.26, 2.15)
0.59
ESRD or dialysis
0.11
0.08
1.40 (0.72, 2.71)
0.32
Renal transplant/death
0.01 -
Persistent eGFR decline ≥ 30%*
0.33
0.39
0.84 (0.60, 1.19)
Persistent eGFR decline ≥ 40%*
0.12
0.14
0.87 (0.49, 1.55)
0.65
*≥2 consecutive assessments ≥ 30 days apart
Albuminuria defined as micro (≥30mg/g) or macro (≥300mg/g); CKD, KDIGO CKD stage; eGFR by CKD-EPI equation

12. Renal Parameters Over Time
Lorcaserin
Placebo
eGFR
UACR

13. Summary
On a background of lifestyle interventions in overweight or obese patients at high CV risk, lorcaserin:
Resulted in modest, durable improvement in risk factors, including weight, HbA1c and blood pressure
↓ incident & progressive of renal disease by eGFR and albuminuria
Findings consistent over time and across subgroups

14. Conclusion
Taken together, the findings of CV safety, glycemic benefit and now improved renal status support the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health.

15. Lorcaserin and Renal Outcomes in Obese and Overweight Patients in the
CAMELLIA-TIMI 61 Trial
Benjamin M. Scirica, Erin A. Bohula, Jamie P. Dwyer, Arman Qamar, Silvio E. Inzucchi, Darren K. McGuire, Anthony C. Keech MD, Steven R. Smith,
Sabina A. Murphy, Kyungah Im, Lawrence A. Leiter, Milan Gupta, Tushar Patel, Wenfeng Miao, Carlos Perdomo, Marc P. Bonaca, Christian T. Ruff,
Marc S. Sabatine, and Stephen D. Wiviott for the CAMELLIA-TIMI 61 Steering Committee and Investigators