Transcript Document 7803631

Outline
• History of development program
– Dr. Carol Bosken
• Introduction to efficacy results
• Dr. Carol Bosken
• Efficacy results
• Ms. Feng Zhou
 Safety results and summary
 Dr. Carol Bosken
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
Safety Endpoints
(Study SCO30003)
• Deaths as a result of an Adverse Event
• Adverse events
• Adverse events of special interest
– Respiratory
– Bone mineral density
– Ocular
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
Mean Exposure to Study Drug
(In Weeks)
Study
Placebo
SAL
FP
SFC
SCO30003
111
120
120
125
FSCB3024
39
43
44
44
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
Deaths
(Study SCO30003)
Outcome Death
Time of AE
Time of Death
Efficacy
All-cause
Not Relevant
Day 1-1092
Safety
Deaths
Randomized
related to treatment
AEs
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
Any time after
the AE
Adverse Events Resulting in Death
(Study SCO30003)
% Patients with event
(Rate/1000 treatment years)
Placebo
N=1544
SAL
N=1542
FP
N=1552
SFC
N=1546
9%
(53)
8%
(44)
10%
(59)
7%
(37)
Respiratory
3%
(14)
3%
(15)
4%
(19)
2%
(10)
Cardiac
3%
(14)
2%
(9)
2%
(10)
2%
(9)
Other
3%
(25)
3%
(20)
4%
(31)
3%
(18)
Any event
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
Respiratory Adverse Events
Resulting in Death
(Study SCO30003)
Rate of events/
1000 Treatment yrs
Placebo
N=1544
COPD
Respiratory failure
Pneumonia
Lung Cancer
9.8
3.9
2.7
1.8
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
SAL
FP
SFC
N=1542 N=1552 N=1546
9.1
4.2
2.8
2.8
10.7
6.2
3.4
3.1
6.5
2.1
2.2
3.0
Serious Respiratory Adverse
Events
(Study SCO30003)
Rate of event/1000 Placebo
SAL
treatment years
N=1544 N=1542
FP
N=1552
SFC
N=1546
COPD
Pneumonia
Respiratory failure
168
28
12
146
27
10
151
49
13
135
52
9
Lower respiratory
tract infections
35
33
56
62
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
Common Respiratory Infectious
Adverse Events
(Study SCO30003)
Rate of
event/1000
Treatment years
Placebo
N=1544
SAL
N=1542
FP
N=1552
SFC
N=1546
Nasopharyngitis
86
88
97
97
URI
101
80
88
105
Pneumonia
39
42
69
71
Bronchitis
75
70
81
86
Influenza
31
26
29
29
Oral candidiasis
11
10
46
37
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
Any Lower Respiratory Tract Infection
(Study SCO30003)
35
Probability of Event (%)
Event Rates at 3 Years:
30
Placebo - 26%
25
SAL - 26%
FP - 30%
20
SFC - 34%
15
10
SFC vs. PLA: ∆ = 8%
HR = 1.38
95% CI: (1.2, 1.6)
5
0
0
84
168 252 336 420 504 588 672 756 840 924 1008 1092
Treatment Days
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
Pneumonia
(Study SCO30003)
35
Event Rates at 3 years
Probability of Event (%)
30
Placebo - 12%
SAL - 13%
FP - 18%
SFC - 20%
25
20
SFC vs. PLA: ∆ = 8%
HR = 1.64
95% CI: (1.3, 2.0)
15
10
5
0
0
84
168
252
336
420
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
504
588
672
756
840
924
1008 1092
Non-Pneumonia Lower Respiratory
Infections
(Study SCO30003)
Number of patients with at
least one event
Placebo
SAL
N=1544 N=1542
FP
N=1552
SFC
N=1546
Any event
199
207
225
275
Bronchitis
142
154
168
202
Lower Respiratory Tract
infection
46
46
43
53
Tuberculosis
10
4
8
12
Bronchiectasis
1
1
2
4
4
3
Fungal infections
Other
2
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
1
Non-pneumonia Lower Respiratory
Infections
(Study SCO30003)
35
Event Rate at 3 years
Probability of Event (%)
30
Placebo - 16%
SAL - 15%
FP - 16%
SFC - 20%
25
20
SFC vs. PLA: ∆ = 4%
HR = 1.23
95% CI: (1.0, 1.5)
15
10
5
0
0
84
168
252
336
420
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
504
588
672
756
840
924
1008 1092
Rate of Antibiotic- and SteroidTreatment Exacerbations
(Study SCO30003)
RR
SFC
95% CI
SFC vs. PLA
Exacerbations/
year
Placebo
SAL
FP
Antibiotic-only
0.32
0.31
0.39
0.37
1.15
1.03, 1.29
Steroid treated
0.80
0.64
0.52
0.46
0.57
0.41, 0.64
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
Summary - Survival
• All cause mortality
–
–
–
–
2.6% difference between placebo and Advair
Less benefit in the US population
Less benefit in high risk patients
No difference between Advair and Salmeterol
• COPD-related mortality
– 1.3% difference between placebo and Advair
• Suggestion that the death rate in FP-treated
patients higher than placebo
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
Summary - Exacerbations
• In both Study SCO30003 and SFCB3024 Advair
decreased the rate of moderate/severe
exacerbations when compared to placebo
• In Study SCO30003, but not SFCB3024, Advair
decreased the rate of moderate/severe
exacerbations when compared to the components,
fluticasone and salmeterol
• Advair decreased the rate of severe exacerbations
in Study SCO30003, but the decrease was not a
great as seen with salmeterol treatment
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
Summary-Adverse Events
• COPD exacerbations, reported as adverse events,
were decreased in the Advair-treated patients
• Respiratory tract infections were increased in
patients treated with a fluticasone-containing
regimen in Study SCO30003
• Antibiotic-treated exacerbations were increased in
patients treated with a fluticasone-containing
regimen in Study SCO30003
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
Risk/Benefit Balance
• Effect of Advair 500/50 mcg BID on
survival
– Statistically borderline
– Not superior to salmeterol
– Fluticasone may be exerting a
detrimental effect
• Would a lower dose of fluticasone result
in a better risk/benefit ratio
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
Risk/Benefit Balance
• Advair effect on Exacerbations
– Effective in moderate, corticosteroidtreated exacerbations
– Less effective in severe
exacerbations.
• Not consistently better than
components
– Increased risk of antibiotic-treated
exacerbations
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007
• Increased risk of respiratory infections
Thank You!
****
Pulmonary-Allergy Drugs Advisory Committee
May 1, 2007