Pulmonary - Allergy Drugs Advisory Committee Meeting

1/17/02


Click here to start


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

Author: stj11454