1	Atazanavir NDA 21- 567 ANTIVIRAL DRUGS ADVISORY COMMITTEE May 13, 2003
2	Protease Inhibitors for HIV Treatment Six marketed protease inhibitors SQV, RTV, IDV, NFV, APV, LPV/RTV Class effects include: lipid elevations lipodystrophy diabetes/hyperglycemia
3	Atazanavir vs Other PIs: Similarities and Potential Differences Class effects Treatment with atazanavir resulted in less of an increase in lipid parameters compared to nelfinivir in phase 2 studies Findings confirmed in phase 3 studies Lipodystrophy/diabetes seen in atazanavir clinical trials
4	Atazanavir vs Other PIs: Similarities and Potential Differences Hyperbilirubinemia (indirect) UGT 1A1 inhibition Similar mechanism to IDV Incidence > 75% Grades 1- 4 Grade 3- 4 T.bilirubin 40% Incidence with IDV about 10% QT/PR prolongation Resistance Profile
5	Atazanavir for HIV Treatment 2 principal studies 034 - naïve (n=810) - 48 wk data 043 - treatment experienced (n= 300) 045 - highly treatment experienced RTV boosted regimen only 16 week data submitted reviewed for safety only Phase 2 trials - 007 and 008 (48 + wk data)
6	Advisory Committee Issues Safety and efficacy of atazanavir hyperbilirubinemia QT/PR prolongation lipid effects Results in treatment experienced population Resistance assessment
7	Advisory Committee Agenda 8:15 a.m. Opening remarks 8:30 a.m. Evaluation of QT interval 8:45 a.m. BMS Presentation 10:00 a.m. Clarifying Questions 10:15 a.m. Break 10:30 a.m. FDA Presentation Kendall A. Marcus, M.D. Thomas Hammerstrom, Ph.D. Lisa K. Naeger, Ph.D. 11:30 a.m. Questions 12:00 p.m. Lunch 1:00 p.m. Open Public Hearing 2:00 p.m. Charge and Questions to the Committee 5:00 p.m. Adjourn