Table of Contents
Pulmonary - Allergy Drugs Advisory Committee Meeting
FLOVENT® DISKUS® and ADVAIR DISKUS®
sNDAs for FLOVENT DISKUS and ADVAIR DISKUS
SEREVENT® (salmeterol xinafoate)
FLOVENT (fluticasone propionate)
ADVAIR DISKUS (fluticasone propionate and salmeterol inhalation powder)
Impact of COPD in the US
Global Initiative for Chronic Obstructive Lung Disease
Clinical Effects of ICS in COPD
Current Use of ICS for COPD: Prescription Data from July 2001
SUMMARY
Order of GSK Presentation
PPT Slide
Scientific and Clinical Rationale
Pathology of COPD
Pathophysiological Features of COPD
Inhaled Corticosteroids
Anti-Inflammatory Effects of ICS in COPD
Fluticasone Propionate Reduces Total Cell Counts and Neutrophils in the Sputum of COPD Patients
ICS (FP) Reduces Inflammation in COPD
Inhaled Corticosteroids
Clinical Effects of ICS in COPD
PPT Slide
Fluticasone Propionate Significantly Improves Pre-dose FEV1 in COPD
Collection of Exacerbation Data in Paggiaro et al., 1998
Fluticasone Propionate Reduces Moderate/Severe Exacerbations in COPD
Inhaled Steroids in Obstructive Lung Disease in Europe (ISOLDE)
FP Improves Post-bronchodilator FEV1 Response in COPD: ISOLDE Study
FP Reduces Median Annual Exacerbation Rate: ISOLDE Study
FP Slows the Decline in Quality of Life as Measured by SGRQ*: ISOLDE Study
ICS (FP) Reduces Inflammation in COPD
Salmeterol in COPD
Salmeterol is a Long-Acting Bronchodilator in COPD
Salmeterol Reduces Airway Obstruction in COPD
Combined Effects of Salmeterol and FP in COPD
PPT Slide
Salmeterol Potentiates the Effect of FP on TNF?-induced IL8 Release from Airway Smooth Muscle Cells
Rationale for Combining FP with Salmeterol
PPT Slide
Clinician’s Perspective
Overview
Diagnosis of COPD
Bronchodilator Response in COPD Intermittent Positive Pressure Breathing Trial (IPPB)
Bronchodilator Response in COPD IPPB Trial
Demographic and Reversibility Data from Clinical Trials in COPD
Efficacy Measures Used to Assess Treatment Response in COPD
PPT Slide
Other Efficacy Measures Observed with Combivent
Other Efficacy Measures Observed with Serevent MDI
Global Initiative for Chronic Obstructive Lung Disease
GOLD: Recommendations for ICS Use
A Physician’s Perspective on Treatment of COPD
CONCLUSIONS
PPT Slide
Overview of Clinical Program
Topics of Presentation
Definitions
Overview of Clinical Program
Study Design: FLTA3025
Study Design: SFCA3006
Study Design: SFCA3007
Key Inclusion Criteria
Key Exclusion Criteria
Primary Efficacy Measures
Secondary Efficacy Measures
Primary Analysis
Patient Demography and Baseline Characteristics Were Similar Across Treatment Groups
FLOVENT EFFICACY RESULTS
FLOVENT
FLTA3025: Dose-Related Increases in Pre-Dose FEV1 Were Seen with FP Treatment vs. Placebo
SFCA3006: Significantly Greater Improvement in Pre-Dose FEV1 Seen with FP500 vs. Placebo
SFCA3007: Significantly Greater Improvements in Pre-Dose FEV1 Seen with FP250 vs. Placebo
SFCA3007: Additional Evidence of Improvements in Pre-Dose FEV1 with FP250
Change in Pre-dose FEV1 (mL) for FP at Endpoint in Reversible/Non-Reversible Patients
Greater Improvements Seen for Most Secondary Efficacy Measures with FP vs Placebo
FLOVENT EFFICACY SUMMARY
ADVAIR EFFICACY RESULTS
ADVAIR
SFCA3006: Significantly Greater Improvement in Pre-Dose FEV1 Seen with FSC500/50 vs. SAL50
SFCA3006: Significantly Greater Improvement in Pre-Dose FEV1 Seen with FSC500/50 vs. SAL50
SFCA3007: Significantly Greater Improvements in Pre-Dose FEV1 Seen with FSC250/50 vs. SAL50
SFCA3007: Significantly Greater Improvements in Pre-Dose FEV1 Seen with FSC250/50 vs. SAL50
ADVAIR
SFCA3006: Significantly Greater Improvements in Post-Dose FEV1 Seen with FSC500/50 vs. FP500
SFCA3006: Significantly Greater Improvements in Post-Dose FEV1 Seen with FSC500/50 vs. FP500
SFCA3007: Significantly Greater Improvements in Post-Dose FEV1 Seen with FSC250/50 vs. FP250
SFCA3007: Significantly Greater Improvements in Post-Dose FEV1 Seen with FSC250/50 vs. FP250
Change in FEV1 (mL) for FSC at Endpoint in Reversible/Non-Reversible patients
Similar Improvements Seen in Secondary Efficacy Measures for FP and SAL vs. PLA
Greater Improvements Seen for Almost All Secondary Efficacy Measures with FSC vs. Placebo
SFCA3006: Significantly Greater Improvement in TDI Score Seen with FSC500/50 vs. SAL50 and PLA
Treatment with FSC250/50 Led to Greater Increase in AM PEF Within 1 Day
ADVAIR EFFICACY SUMMARY
SAFETY RESULTS Flovent / Advair
Safety Exposure
Adverse Events Occurred at Similar Frequency Across Treatment Groups
Similar Adverse Events of Special Interest Except for Expected Topical Effects of ICS
Comparable Incidence of Pneumonia Across Treatment Groups
HPA Axis Monitoring (Performed in a Subset of Patients)
No Clinically Significant Difference in HPA Axis Results Between FSC and Individual Agents or Placebo
SUMMARY OF SAFETY RESULTS
Long-term Safety Data with FP
The Range of Systemic Exposure with FP Diskus in COPD is Not Greater Than FP CFC MDI in Asthma
Clinical Studies Examining BMD and/or Ophthalmic Effects of FP in Patients with Asthma
Mean Percent Change in Lumbar Spine BMD was Similar Between FP Groups Compared to Placebo
No Evidence of Cataracts or Glaucoma was Seen with FP versus Placebo Treatment
BMD Results from Clinical Trials Comparing FP MDI vs. Other ICS
ISOLDE: Adverse Events of Special Interest
Summary Long-term Safety Data with FP
Proposed Dosage and Administration Recommendations
CONCLUSIONS
PPT Slide
Summary Remarks
COPD is a Significant Public Health Problem in the US
Current Therapeutic Management of COPD
Combined Effects of Salmeterol and FP in COPD
Advair Diskus / Flovent Diskus
Pulmonary - Allergy Drugs Advisory Committee Meeting
External Experts
PPT Slide
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