Biologics License Application: Recombinant Human Activated Protein C (rhAPC) [drotrecogin alfa (activated)] Xigris™ for Severe Sepsis

10/17/01


Click here to start


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

Author: CBER