TENOFOVIR DF

10/17/01


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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

Author: CDER USER