Table of Contents
Biologics License Application: Recombinant Human Activated Protein C (rhAPC) [drotrecogin alfa (activated)] Xigris™ for Severe Sepsis
Sponsor’s Proposed Indication
Overview of Drotrecogin Product Development
Overview of Drotrecogin Product Development
Study Design: Phase 2 Study
Results: Phase 2 Study
Study Design: Phase 3 Study
Study Design: Final Statistical Analysis Plan
Study Design: Prospectively Defined Secondary Analyses
Results: Demographics Age, Gender, Origin
Results: Demographics Disease Severity
Results: Demographics Disease Severity
Results: Demographics Disease Severity
Results: Demographics Disease Severity
Results: Phase 3 Study Primary Efficacy Endpoint
Results: Primary Efficacy Endpoint ITT Population
Review of Mortality Effect by Patient Subgroups
Results: Mortality as a Function of Age
Results: Mortality as a Function of Age
Review of Mortality Effect by Patient Subgroups
APACHE II: Disease severity
Results: Mortality as a Function of APACHE II at Study Entry
Results: Mortality as a Function of APACHE II
Results: Mortality as a Function of APACHE II Quartiles
Results: Mortality as a Function of Organ Failure
Results: Mortality as a Function Disease Severity (Organ Failure)
Mortality as a Function of Shock
Results: Summary of Treatment Effect by APACHE II & Organ Failure & Shock
Review of Mortality Effect by Patient Subgroups
Results: Mortality as a Function of Protein C Levels
Results: Mortality in Patients with Laboratory Evidence of DIC
Review of Mortality Effect by Patient Subgroups
Results: Mortality as a Function of Heparin Use
Morbidity Outcomes
Results: Functional Status at Day 28
Protocol Amendment
Effect of Protocol Change: Original vs. Amended Protocol
Effect of Protocol Change: Original vs. Amended Protocol
Effect of Protocol Change: DNR Orders
Mortality: Original vs. Amended Protocol
Cumulative 28 Day Mortality Over Time
Sensitivity Analysis: Patients on Pre-Amendment Not Eligible Under Post-Amendment
Summary of Efficacy
Summary of Efficacy
Outline of Presentation
Pediatric Database
Pediatric Sepsis Study vs. Adult Phase 3 Type of Organ Failure (% of Patients)
Pediatric Sepsis Study vs. Adult Phase 3 # of Organ Failures (% of Patients)
Pediatric Sepsis Study vs. Adult Phase 3 Primary Site of Infection (% of Patients)
Pediatric Sepsis Study vs. Adult Phase 3 Type of Pathogen (% of Patients)
Pediatric Sepsis Study vs. Adult Phase 3 Predicted Mortality (% of Patients)
Pediatric Sepsis Study vs. Adult Phase 3 Actual Mortality (% of Patients)
Pediatric Sepsis Study vs. Adult Phase 3 Safety Parameters (% of Patients)
Pediatric Safety
Pediatric Summary
Outline of Presentation
Safety Phase 2 Patient Population
Safety Phase 2 Patient Deaths by Treatment Group
Safety Phase 2
Outline of Presentation
Safety Phase 3 Deaths Attributable to Hemorrhage During the Infusion Period
Ongoing Open-Label Trials New Intracranial Hemorrhages During the Infusion Period
Serious Bleeding Events Protocol Definition
Serious Bleeding Events Infusion Period
Safety During the Infusion Period
First APACHE II Quartile Events During Drug Infusion
Subjects Requiring Transfusion During 28 Day Study Period
Serious Bleeding Events in Patients Laboratory Evidence of DIC
Bleeding Events and Baseline Coagulation Factors
Baseline APTT and Adverse Bleeding Events
Baseline PT and Adverse Bleeding Events
Baseline Platelet Count and Adverse Bleeding Events
Serious Bleeding Events in Subjects who Received Heparin (Received DVT prophylactic dose at baseline up to day 5)
Bleeding Adverse Events in Subjects who Received Heparin (Received DVT prophylactic dose at baseline up to day 5)
Subgroups
Baseline Surgical Status Phase 2 and 3 Data
rhAPC Steady State Concentration and Adverse Events (N=326, median 45 ng/ml)
Outline of Presentation
Immunogenicity
Immunogenicity
Patients Positive for Specific anti-APC Ab (Inhibition Assay)
Outline of Presentation
Pediatric Summary
Summary of Safety - Adults
Summary of Safety - Adults
Summary of Safety - Adults
Safety Conclusion
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