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
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