Table of Contents
NDA 21-083 Sirolimus Rapamune ®
FDA Review Team for NDA 21-083
FDA Perspective: Sirolimus (Rapamune®)
Study Population
Strengths of Studies 301 and 302
Strengths of Studies 301 and 302
Study Design
Immunosuppression
Prophylaxis
Co-primary Study Endpoints
FDA Statistical Perspective on Efficacy Analyses
Outline of Presentation
Efficacy Failure at 6 months
Efficacy Failure at 6 months Protocol 301
Efficacy Failure at 6 months Protocol 302
Patient and Graft Survival at 12 months
Patient and Graft Survival at 12 months Protocol 301
Patient and Graft Survival at 12 months Protocol 302
Efficacy Failure at 6 months for Various Subgroups
Efficacy Failure: Race
Efficacy Failure: Donor Source
Efficacy Failure: Recipient Gender
Efficacy Failure: No. of HLA Mismatches
“High Risk” Patients
FDA Defined High Risk Subgroup
Efficacy Failure: High Risk Subgroup
Time to Efficacy Failure
Time to Efficacy Failure Protocol 301
Rejections after 60 days but during the first 6 months
Time to Efficacy Failure Protocol 302
Rejections after 60 days but during the first 6 months
Summary of Efficacy
Summary of Efficacy (cont.)
Safety Perspective
Safety Perspective
Summary of Deaths and Graft Losses at 12 months Protocol 301
Summary of Deaths and Graft Losses at 12 months Protocol 302
Deaths
Discontinuations
Post-transplant lymphoproliferative disease (PTLD)
Infection Studies 301 and 302
Opportunistic Infection
Post-transplant diabetes mellitus (PTDM)
Treatment-emergent Adverse Events Occurring with ᡌ % Frequency
Treatment-emergent Adverse Events Occurring with > 5% and ង % Frequency
Hematologic Adverse Events
Hematologic Adverse Events (cont.)
Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic Purpura (HUS/TTP)
Liver Function Tests (LFT’s)
Hyperlipidemia
Study 301 Cholesterol Analysis
Study 302 Cholesterol Analysis
Study 301 Triglyceride Analysis
Study 302 Triglyceride Analysis
Use of Lipid-lowering Drugs in Treatment of New-onset Hypercholesterolemia
Renal Function
Important Points about Renal Function Assessment
Mean GFR and Mean Serum Creatinine Analysis at 12 Months
Study 301 Mean GFR Results at 12 Months (337-393 days)
Study 301 Serum Creatinine at 12 Months (337-393 days)
Study 302 Mean GFR Results at 12 Months (337-393 days)
Study 302 Serum Creatinine at 12 Months (337-393 days)
Summary on Exploratory Renal Function Analysis
Renal Function - Additional Questions
Study 301 Mean GFR at 12 Months (337-393 days)
Study 302 Mean GFR at 12 Months (337-393 days)
Study 301 Serum Creatinine at 12 Months (337-393 days)
Study 302 Serum Creatinine at 12 Months (337-393 days)
Renal Function
Renal Function (cont.)
Safety Conclusions for Sirolimus
Questions for the Advisory Committee #1
Questions for the Advisory Committee #2
Questions for the Advisory Committee #3
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