Endocrinologic and Metabolic Drugs Advisory Committee Meeting

2/6/03


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Table of Contents

Endocrinologic and Metabolic Drugs Advisory Committee Meeting

Introduction

Sponsor Presentation

Additional Participants

Regulatory History

Development History

Aldurazyme Administration

Proposed Indication

Description of MPS I

Mucopolysaccharidosis I (MPS I) A lysosomal storage disorder

Spectrum of Disease

Heterogeneity in Hurler-Scheie

MPS I Biochemistry

MPS Disorders Biochemistry

Lysosomal Storage in MPS I

Multi-systemic Involvement

Pulmonary Disease

Upper Airway Obstruction

Upper Airway Obstruction

Joint and Skeletal Disease

Joint Restriction and Stiffness

Enlarged Liver and Spleen

Cardiac Disease in MPS I

Eye Disease in MPS I

CNS Disease in MPS I

Current Treatment for MPS I Patients

MPS I Bone Marrow Transplantation

MPS I A lysosomal storage disorder

Aldurazyme Clinical Program

Outline

Clinical Program

Phase 1/2 Study

Phase 1/2: Reduction in Urinary GAG Level

PPT Slide

PPT Slide

Phase 3 Study

Phase 3 Study: Endpoint Considerations

Phase 3 Study: Design

Phase 3 Study: Efficacy Variables

Phase 3 Study: Baseline Patient Characteristics

Phase 3 Study: Baseline Patient Characteristics

Phase 3 Study: Baseline Frequency of Respiratory Disease

Phase 3 Study: Baseline Frequency of Musculoskeletal Disease

Phase 3 Study: Efficacy Results

Phase 3 Study: Aldurazyme Reduces Urinary GAG Levels

Phase 3 Studies: Aldurazyme Reduces Hepatomegaly

Phase 3 Efficacy Variables

Phase 3 Study: Aldurazyme Improves FVC

Phase 3 Study: Clinically Significant Improvement in FVC

Phase 3 Study: Aldurazyme Reduces Sleep Apnea

Phase 3 Efficacy Variables

Phase 3 Study: Aldurazyme Increases 6MWT Distance

Phase 3 Study: Clinically Significant Improvement in 6MWT

Phase 3 Studies: Aldurazyme Increases Shoulder Flexion

Phase 3 Efficacy Variables

Phase 3 Study: Aldurazyme Improves Visual Acuity

Phase 3 Study: Disability and Quality of Life

Post-Hoc Analysis: Composite Endpoint Approach

Post-Hoc Analysis: Composite Endpoint Approach

Phase 3 Study: Composite Endpoint

Phase 3 Study: Post-Hoc Analysis Composite Endpoint

Phase 3 Study: Post-Hoc Analysis Aldurazyme Leads to Net Improvement

Aldurazyme Efficacy Summary

Aldurazyme Efficacy Summary: Improved Respiratory Function

PPT Slide

PPT Slide

Aldurazyme Efficacy Summary: Post-Hoc Composite Endpoint

Safety and Immunogenicity

Safety and Immunogenicity: Summary

Phase 3 Double-Blind: Overall Adverse Events

Phase 3 Study: Infusion Associated Reactions

Phase 3 Study: Immunogenicity

Phase 3 Study: Immunogenicity

Conclusions

Clinical Perspective

Clinical Perspective (points to consider)

Clinical Perspective

Concluding Remarks

Pulmonary Function as Measured by FVC

Functional Capacity as Measured by 6MWT

Demographic Subset Analyses

Effect of Antibodies on Long-Term Efficacy

Use in Patients with Profound Respiratory Impairment

Effect of Antibodies on Clinical Course of Patients with Residual Enzyme Activity

Conclusions

Author: ydugan