# Presentation: 812649

## 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

## Safety Endpoints                (Study SCO30003)

- Deaths as a result of an Adverse Event
- Adverse events
- Adverse events of special interest
- Respiratory
- Bone mineral density
- Ocular

## Mean Exposure to Study Drug           (In Weeks)

| Study | Placebo | SAL | FP | SFC |
| --- | --- | --- | --- | --- |
| SCO30003 | 111 | 120 | 120 | 125 |
| FSCB3024 | 39 | 43 | 44 | 44 |

## Deaths                                                        (Study SCO30003)

|  Outcome |  Death | Time of AE | Time of Death |
| --- | --- | --- | --- |
| Efficacy | All-cause | Not Relevant | Day 1-1092 |
| Safety | Deaths related to AEs | Randomized treatment | 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 |
| --- | --- | --- | --- | --- |
| 
Any event | 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) |

##  Respiratory Adverse Events Resulting in Death                               (Study SCO30003)

| Rate of events/ 1000 Treatment yrs | Placebo
N=1544 | SAL
N=1542 | FP
N=1552 | SFC
N=1546 |
| --- | --- | --- | --- | --- |
| COPD
Respiratory failure
Pneumonia
Lung Cancer | 9.8
3.9
2.7
1.8 | 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 treatment years | Placebo
N=1544 | SAL
N=1542 | FP
N=1552 | SFC
N=1546 |
| --- | --- | --- | --- | --- |
| COPD   
Pneumonia
Respiratory failure

Lower respiratory    
       tract infections | 168
28
12

35 | 146
27
10

33 | 151
49
13

56 | 135
52
9

62 |

## 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
URI
Pneumonia
Bronchitis
Influenza
Oral candidiasis | 86
101
39
75
31
11  | 88
80
42
70
26
10 | 97
88
69
81
29
46 | 97
105
71
86
29
37 |

## Any Lower Respiratory Tract Infection                (Study SCO30003)

**Any Lower Respiratory Tract Infection**                (Study SCO30003)

## Pneumonia(Study SCO30003)

## Non-Pneumonia Lower Respiratory Infections                                            (Study SCO30003)

| Number of patients with at least one event | Placebo
N=1544 | SAL
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 |
| Fungal infections |   |   | 4 | 3 |
| Other |   | 2 |   | 1 |

**Non-Pneumonia Lower Respiratory Infections****                                            **(Study SCO30003)

## Non-pneumonia Lower Respiratory    Infections                                                 (Study SCO30003)

##  Rate of Antibiotic- and Steroid- Treatment Exacerbations (Study SCO30003)

| 
Exacerbations/ year | 
Placebo | 
SAL | 
FP | 
SFC | RR
95% CI
SFC vs. PLA |
| --- | --- | --- | --- | --- | --- |
| 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 |

## 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

## 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

## 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

## 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

## Risk/Benefit Balance

- Advair effect on Exacerbations
- Effective in moderate, corticosteroid-treated exacerbations
- Less effective in severe exacerbations.
- Not consistently better than components
- Increased risk of antibiotic-treated exacerbations
- Increased risk of respiratory infections

## 

		Thank You!

**	****	****Thank You!**

*******