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Transcript of 1540_KlausFRabe
10/08/2012
ALAT Montevideo 2012
New Drugs for COPD Klaus F. Rabe
Krankenhaus Grosshansdorf & CAU Kiel
Hansel TT, Lancet 2009
Bronchitis Bronchiolitis
ALAT Montevideo 2012
New Drugs for COPD
4
Nutrition
Infections
Socio-economic status
Aging Populations
ALAT Montevideo 2012
New Drugs for COPD
Pauwels RA and Rabe KF, Lancet 2004;364:613-620
Adapted from GOLD
ALAT Montevideo 2012
New Drugs for COPD: Why?
Wissam M. et al., Proc Am Thorac Soc 2008;5:549-555
What do Patients with COPD die from?
Author
Mannino et al Hansell et al Camilli et al Huiart et al Anthonisen et al Zielinski et al Waterhouse et al Keistinen et al Vilkman et al Celli et al
Reported causes of mortality in patients with COPD (%)
Site
USA
England Tucson Canada
USA Europe Europe Europe Europe
USA, Spain, Venezuela
Patients with COPD Dying
1.1 million
312,000 86
2,000 149 215 103 973
1,070 162
Cause: COPD (%)
43 60 23 14
<15 38 49 22 30 61
Cause: Cardiovasc (%)
26 26 42 38 25 27 22 37 37 14
Cause: Malign (%)
8 8 9 -
60 7
21 21 20 12
Cause: Other Respiratory (%)
- 4
26 - -
21 - 4 - -
GOLD 2011/2012
Hansel TT, Lancet 2009
ALAT Montevideo 2012
New Drugs for COPD
Innovations for the Teatment of COPD…?
Others
18 month approval assumption for all products. Competitive products could be approved within one review cycle (10 months) resulting in an eight month earlier launch. Flutiform will initially launch with asthma indication
Indacaterol QD LABA
07/10
Aclidinium Br 09/12
LAMA 06/13
QD Advair LABA+ICS
04/14 QD LABA
11/13
Generic Advair BID LABA+ICS
2012
QD Triple
QMF149 QD LABA+ICS
07/14
T+1744 & 1744 Mono LAMA+LABA
01/13
QD LAMA & LAMA+LABA
02/14
Novel Anti-Inflammatory
Agents
1st QD LABA
1st QD LABA+ICS
QD Triple
QD Triple
QVA149 QD LABA+LAMA
06/13
2012 2013 2014 2009 2010 2011 2015 2005-2008
LAMA+ICS LAMA+LABA 06/14
Symbicort First Patent Expires
LABA+ICS 09/2012
Spiriva Patent Expires (1/18)
LABA+ICS
Source: Business Intelligence
Symbicort COPD LABA+ICS (AZ), 02/09
Flutiform (asthma) LABA+ICS
(ABBOTT), 2010
Daxas Oral PDE-IV (QD)
(Nycomed) 2010
QVA 149 -Pharmacotherapy of COPD V3.0
Hansel TT, Lancet 2009
New Drugs for COPD: Role of Exacerbations
Hurst JR et al. N Engl J Med 2010;363:1128-1138
ASSOCIATION OF DISEASE SEVERITY WITH THE FREQUENCY
AND SEVERITY OF EXACERBATIONS
Hurst JR et al. N Engl J Med 2010;363:1128-1138
Vogelmeier C et al. N Engl J Med 2011;364:1093-1103
MACROLIDE (AZITHROMYCIN) STUDY PROPORTION OF PARTICIPANTS FREE OF ACUTE EXACERBATIONS OF COPD
Albert RK et al. N Engl J Med 2011;365:689-698.
Fabbri LM, Rabe KF. Eur Respir J 2008;31:204-212
ALAT Montevideo 2012
New Drugs for COPD
Statin Therapy and Mortality: Peripheral Arterial Disease With Associated COPD
Van Gestel YRBM et al., Am J Cardiol 2008;102:192-196
50
75
100
25
0 0 2 4 6 8 10
No COPD / Statins
No COPD / no Statins
COPD / Statins
COPD / no Statins
Surv
ival
(%)
Follow-up (years) Number at risk No COPD Mild COPD Moderate COPD Severe COPD
1545 476 961 327
1223 348 667 208
1018 224 505 107
824 154 345 60
610 106 229 39
433 55 145 18
Abdominal Obesity and CVD risk
Atherogenic Dyslipidemia Triglycerides HDL cholesterol
Cholesterol/HDL cholesterol ratio "Normal" LDL cholesterol but apo B
Small, dense LDL and HDL Postprandial hyperlipidemia
Insulin Resistance Insulin resistance Hyperinsulinemia
Hyperglycemia Type 2 diabetes
Thrombotic State PAI-1
Fibrinogen
Inflammatory State Leptin CRP
Cytokines Abdominal Obesity Metabolic Risk Factors
Inflammation
Thin fibrous cap
Lipid Core
Coronary Atherosclerosis Unstable Plaque
Adapted from Després JP, et al. Progress in Obesity Research: 9; 2003:29-35.
Risk of Acute Coronary Syndrome
Young RP et al., Eur Respir J 2007;30:616-622
0
2
4
6
8
Odd
s ra
tio
>100 80 - 100 65 - 79 <65
FEV1 % pred
0
10
20
30
40
50
60
70
80
Mor
talit
y ra
te %
<50 50 - 70 70 - 90 90 - 110 >100
FEV1 height adjusted
current smoker ex-smoker never smoker
heavy smoker moderate smoker ex- smoker non-smoker
CV mortality Overall mortality
ALAT Montevideo 2012
New Drugs for COPD
Time to Onset of First Major Adverse CV Event:
Effect of PDE4 Inhibition Roflumilast 500 mcg, od, p.o. + Roflumilast 250 mcg, od p.o.
placebo, od, p.o.
Prob
abili
ty o
f eve
nt
0.00
0.02
0.04
0 30 60 90 120 150 180 210 240 270 300 330 360 390
Days post-randomisation
0.01
0.03
*MACE : CV death, non-fatal MI, non-fatal stroke White WB, et al. submitted
Weight Decrease In Obese Patients with COPD
Percent weight change from baseline to end of treatment by BMI at baseline: pivotal COPD studies pool (SAF)
Calverley PMA, Rabe KF, Goehring UM, et al. Lancet 2009;374:685–694. (supplementary webappendix).
Roflumilast and Glucose Homeostasis in Diabetes
Wouters et al, Endocrinology 2012
Roflumilast and Glucose Homeostasis in Diabetes
Wouters et al, Endocrinology 2012
10/08/2012
Safety and tolerability of NVA237, a Once Daily Long-acting Muscarinic Antagonist, in Patients with COPD
Placebo (n=91) NVA237 100 μg (n=92) NVA237 200 μg (n=98)
Peak FEV1 defined as the maximum value up to 5 hours post-dose Data are presented as least squares mean + SE; *p<0.05 vs placebo
Pea
k FE
V1 (
L) * * * *
1,2
1,4
1,6
1,8
Day 1 Day 28
Stan
dard
ized
AU
C o
f FE
V1
(L)
(5
min
–5
h p
ost-
dose
)
* * * *
1,2
1,4
1,6
1,8
Day 1 Day 28