1	Tipranavir NDA 21-814 Antiviral Drugs Advisory Committee May 19, 2005
2	HIV Drug Resistance Different patient populations Naïve subjects harboring resistant virus Limited or Intermediate prior treatment with resistance Extensive prior treatment with resistance with limited treatment options
3	HIV Drug Resistance in the U.S. Treatment-experienced subject cohort with VL > 500 copies/ml from HIV Cost and Service Utilization Study (Richman, et al, AIDS, 2004) Overall resistance was 76% 2-class resistance = 48% 3-class resistance = 13%
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5	Current State of Therapy for Patients with Limited Treatment Options Enfuvirtide(T-20) Traditional approval 2004 Drugs in antiviral pipeline Tipranavir 2 key studies in a highly treatment experienced population
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7	Tipranavir/r: Trial Design Resist 1 and Resist 2 Open label TPV/r + OBR vs CPI/r + OBR Amended protocol allowed patients with PI resistant virus to receive a PI-based regimen Analyzed as superiority trials Escape clause @ week 8 to allow subjects with VF to receive TPV in 1182.17 Loss of control arm @ week 8
8	Tipranavir/r: Patient Population Highly treatment experienced 3 class experienced Median number of 12 prior antiretroviral drugs Prior T-20 use in 12% Baseline resistance 97% of isolates resistant to at least 1 PI 95% of isolates resistant to at least 1 NRTI 75% of isolates resistant to at least 1 NNRTI
9	Tipranavir/r: FDA Presentation Efficacy evaluation Resistance evaluation Exposure-response data Drug-drug interactions CYP 3A inhibitor PgP inducer Safety profile Hepatoxicity Rash Hyperlipidemia Summary
10	NDA 21-814 Review Team Clinical Statistical Jeff Murray Greg Soon Rosemary Johann-Liang Rafia Bhore Andrea James Susan Zhou Melisse Baylor Neville Gibbs Virology Toxicology Jules O’Rear James Farrelly Lisa Naeger Anita Bigger Kim Struble Chemistry Clin. Pharmacology Stephen Miller Kellie Reynolds Ko Yu-lo Derek Zhang Jenny J. Zheng Joga Gobburu Project Management Tanima Sinha