Table of Contents
TENOFOVIR DF
Advisory Committee Issues
Advisory Committee Issues
Advisory Committee Issues
Advisory Committee Issues
Advisory Committee Issues
VIREADTM NDA
Advisory Committee Issues
Advisory Committee Agenda
NDA 21-356 Tenofovir Disoproxil Fumarate
Presentation Outline
NDA Overview
NDA Submission: Four Clinical Studies
Principal Studies: 902 and 907
Primary Efficacy Endpoint
HIV RNA Results: Placebo vs Tenofovir 300 mg
Mean Change From Baseline: HIV RNA
Proportion < 400 and < 50 copies/mL
CD4 Cell Count Results: Placebo vs Tenofovir 300 mg
CD4 Response: Study 902
CD4 Response: Study 907
CD4 Response by Baseline CD4: Studies 902 and 907
Efficacy Summary
Efficacy Summary (cont.)
Clinical Virology Results
Clinical Virology
Clinical Virology: Limitations of FDA Analyses
Genotypic Results
Genotypic Results
PPT Slide
PPT Slide
PPT Slide
PPT Slide
HIV RNA Response by # of Baseline TAMs: Mean DAVG24 (N)
Other NRTI Mutations and HIV RNA Response
Phenotypic Results
Phenotypic Analyses
Resistance Summary
Resistance Summary
Safety Summary
Safety Summary
Nonclinical Assessment of Bone Abnormalities
Toxicity in Rat and Dog Four Week Gavage Studies
Toxicity in Rat 42 Week Gavage Study
Toxicity in Dog 42 Week Gavage Study
Toxicity in Mouse 13 Week Gavage Study
Intravenous Study in Cynomolgus Monkeys
Rhesus Monkey Efficacy Studies
Rhesus Monkey Efficacy Studies, Cont.
Rhesus Monkey Efficacy Studies, Cont.
Reproductive Toxicology Studies
Conclusions
Conclusions, Cont.
Clinical Assessment of Bone Abnormalities
Animal Exposures in Relation to Human Exposures
Clinical Assessment of Bone Abnormalities
Incidence of Clinical Fractures:
PPT Slide
Clinical Assessment of Bone Abnormalities
Clinical Assessment of Bone Abnormalities
Traditional Approval:
Traditional Approval Plans
Two - Part Hybrid (N=100)
Summary of Regulatory Issues
Summary of Regulatory Issues: Indication
Summary of Regulatory Issues: Indication
Summary of Regulatory Issues: Bone Abnormalities
Summary of Regulatory Issues: Bone Abnormalities
Summary of Regulatory Issues: Bone Abnormalities
Summary of Regulatory Issues: Clinical Virology
Summary of Regulatory Issues: Clinical Virology
Summary of Regulatory Issues: Accelerated Approval and Phase 4 Commitments
Tenofovir Review Team
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