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Antiviral Drugs Advisory Committee Meeting

Antiviral Drugs Advisory Committee Meeting. Raltegravir NDA 22-145 September 5, 2007. NDA 22-145 : Isentress™ (raltegravir potassium) Applicant : Merck & Co., Inc. Formulation : 400 mg tablets Indication : HIV-1 treatment-experienced adult patients.

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Antiviral Drugs Advisory Committee Meeting

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  1. Antiviral Drugs Advisory Committee Meeting Raltegravir NDA 22-145 September 5, 2007

  2. NDA 22-145: Isentress™ (raltegravir potassium) Applicant: Merck & Co., Inc. Formulation: 400 mg tablets Indication: HIV-1 treatment-experienced adult patients

  3. Antiretroviral ArmamentariumFive Approved Classes • 3 NNRTIs • 7 NRTIs • 9 PIs • 1 Fusion inhibitor • 1 CCR5 receptor antagonist ___________________________________ > 20 approved agents

  4. DLV NVP EFV SQV.hgc NFV LPV/r SQV.sgc APV ATV RTV FPV IDV Approved Antiretrovirals 3TC/ZDV TDF 3TC/ABC FTC/TDF ddC 3TC ABC TDF/FTC/EFV ZDV ddI d4T ABC/3TC/ZDV FTC 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 T-20 MVC NRTI PI TPV NNRTI DRV FI CCR5 Courtesy of C. Fletcher slide courtesy of C. Fletcher

  5. Maturevirus Fusion inhibitors Proteaseinhibitors Integrase inhibitors Reverse transcriptase inhibitors Antiretroviral Armamentarium: Novel Agents in Clinical Development clinicaloptions.com/hiv

  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. 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 NDA 22-145 Review Team

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