1	Antiviral Drugs Advisory Committee Meeting Raltegravir NDA 22-145 September 5, 2007
2	"NDA 22-145" NDA 22-145: Isentress™ (raltegravir potassium) Applicant: Merck & Co., Inc. Formulation: 400 mg tablets Indication: HIV-1 treatment-experienced adult patients
3	Antiretroviral Armamentarium Five Approved Classes 3 NNRTIs 7 NRTIs 9 PIs 1 Fusion inhibitor 1 CCR5 receptor antagonist ___________________________________ > 20 approved agents
4	Approved Antiretrovirals
5	Antiretroviral Armamentarium: Novel Agents in Clinical Development
6	Antiretroviral Armamentarium: Integrase Inhibitor Integrase is one of three HIV-1 enzymes required for viral replication Results in integration of HIV-1 DNA into host cell genome Raltegravir targets viral integrase blocks strand transfer step, thus inhibiting viral replication
7	Raltegravir: Clinical Development Program Protocols 004/005: Phase 2 dose-finding trials in naïve/treatment-experienced patients, respectively Protocols 018/019: Identical double-blind, placebo-controlled Phase 3 trials in HIV-1 treatment-experienced patients Week 16 primary endpoint because Phase 2 trials demonstrated robust activity Allowed to submit NDA with 100% of Week 16 data and about 60% of Week 24 data
8	Agenda Merck Introduction Background Clinical Development Program Efficacy Resistance Safety Drug interactions Risk Management Plan Conclusions FDA Summary of clinical efficacy, resistance and clinical safety Concluding remarks
9	Issues for Committee Discussion Adequacy of evidence of safety and efficacy Any gaps in data or other needed information? Safety areas of interest Risk of malignancies Others Impact of raltegravir on design of future antiretroviral Phase 3 clinical trials for treatment-experienced subjects
10	NDA 22-145 Review Team Clinical Sarah Connelly Kendall Marcus Jeff Murray Debra Birnkrant Statistical Karen Qi Fraser Smith Greg Soon Virology Sung Rhee Jules O’Rear Project Management Monica Zeballos Pharmacology/Toxicology Ita Yuen Hanan Ghantous Clinical Pharmacology Derek Zhang Pravin Jadhav Shashi Amur Jogarao Gobburu Kellie Reynolds John Lazor Chemistry George Lunn Ted Chang Stephen Miller Office of Safety and Epidemiology Melissa Truffa Paula Gish Mary Willy Catherine Dormitzer