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Rilpivirine ( Edurant ): A New NNRTI

Rilpivirine ( Edurant ): A New NNRTI. David Spach, MD Clinical Director, Northwest AETC Professor of Medicine, University of Washington. Presentation Prepared by: David Spach, MD Last Updated: July 8, 2011. Antiretroviral Therapy. Rilpivirine ( Edurant ). ANTIRETROVIRAL THERAPY.

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Rilpivirine ( Edurant ): A New NNRTI

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  1. Rilpivirine (Edurant): A New NNRTI David Spach, MDClinical Director, Northwest AETCProfessor of Medicine, University of Washington Presentation Prepared by: David Spach, MDLast Updated: July 8, 2011

  2. Antiretroviral Therapy Rilpivirine (Edurant)

  3. ANTIRETROVIRAL THERAPY Rilpivirine (Edurant)* • Class: non-nucleoside reverse transcriptase inhibitor • Approval: FDA-approved May 20, 2011 • Indication: in combination with other ARVs for treatment-naïve adults • FDA Approved Dose/Formulation^: 25 mg tablet (with a meal) • Co-Formulation (in development): Tenofovir-Emtricitabine-Rilpivirine • Metabolism: primarily in liver via cytochrome P450 (CYP 3A4) enzymes • Pregnancy : category B • Adverse Events (low): depression, insomnia, headache, and rash * Formerly TMC-278^The dosage form contains rilpivirine hydrochoride 27.5 mg (equivalent to 25 mg of rilpivirine)

  4. Summary of Key Rilpivirine (Edurant) Studies • Phase 2b Trial- C204 Dose Ranging Study: Rilpivirine versus Efavirenz • Phase 3 Trials- ECHO (TMC278-C209): Rilpivirine versus Efavirenz- THRIVE (TMC278-C215): Rilpivirine versus Efavirenz

  5. Rilpivirine vs. EfavirenzTMC-278-C204 Dose-Ranging Study

  6. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive TMC-278-C204: Study Design Rilpivirine: 25 mg qd(n = 93) Rilpivirine: 75 mg qd(n = 95) 1x Rilpivirine: 150 mg qd(n = 91) Efavirenz: 600 mg qd(n = 89) *2 NRTIs: Zidovudine + Lamivudine (75%); Tenofovir + Emtricitabine (25%) Source: Pozniak AL, et al. AIDS. 2010;24:55-65.

  7. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive TMC-278-C204: Week 96 Results 48 and 96 Week Data: Virologic Response ( ITT) All regimens included 2 NRTIs: Zidovudine + Lamivudine (75%); Tenofovir + Emtricitabine (25%) Source: Pozniak AL, et al. AIDS. 2010;24:55-65.

  8. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive TMC-278-C204: Conclusion Source: Pozniak AL, et al. AIDS. 2010;24:55-65.

  9. Rilpivirine vs. EfavirenzECHO and THRIVE Studies

  10. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive ECHO and THRIVE: Study Design Rilpivirine: 25 mg qd + TDF/FTC(n = 346) ECHO 1x Efavirenz: 600 mg qd + TDF/FTC(n = 344) Rilpivirine: 25 mg qd + 2NRTIs*(n = 340) THRIVE 1x Efavirenz: 600 mg qd + 2NRTIs*(n = 338) *2 NRTIs: ECHO: Tenofovir + Emtricitabine (TDF/FTC)THRIVE: Tenofovir + Emtricitabine; Zidovudine+ Lamivudine; Abacavir + Lamivudine Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.

  11. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive ECHO and THRIVE: Week 48 Results 48 Week Data: Virologic Response ( ITT-TLOVR) All regimens included 2 NRTIs Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.

  12. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive ECHO and THRIVE: Week 48 Results Pooled ECHO and THRIVE: Virologic Response ( ITT-TLOVR) 84.3% 82.3% 2NRTIs+ Rilpivirine (n = 686) 2NRTIs+ Efavirenz (n = 682) Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.

  13. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive ECHO and THRIVE: Week 48 Results Virologic Response with Baseline HIV RNA > 100,000 copies/ml All regimens included 2 NRTIs Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.

  14. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive ECHO and THRIVE: Week 48 Results Virologic Response with Baseline HIV RNA < 100,000 copies/ml All regimens included 2 NRTIs Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.

  15. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive ECHO and THRIVE: Results 48 Week Data: Virologic Failure All regimens included 2 NRTIs Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.

  16. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive ECHO and THRIVE: Results 48 Week Data: Discontinuation Due to Adverse Effects All regimens included 2 NRTIs Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.

  17. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive ECHO and THRIVE: Results NOTE: 31 (50%) of 62 rilpivirine failure isolated were phenotypically resistant to rilpivirine Of these, 90% phenotypically cross-resistant to etravirine Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.

  18. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive ECHO and THRIVE: Results Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.

  19. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive ECHO and THRIVE: Resistance Results Most Frequent NNRTI Resistance Associated Mutations (RAMs) Source: Rimsky L, et al. 50th ICAAC. 2010:H-1810.

  20. ANTIRETROVIRAL THERAPY Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive ECHO and THRIVE: Resistance Data Most Frequent NRTI Resistance Associated Mutations (RAMs) Source: Rimsky L, et al. 50th ICAAC. 2010:H-1810.

  21. ANTIRETROVIRAL THERAPY Rilpivirine Active Against Wild-Type and NNRTI-Resistant HIV-1 • Sensitivity not affected by most single NNRTI resistance-associated mutations: 100, 103, 106, 138,179,188,190, 221, 230, 236 • Decreased activity associated with: K101P, Y181I/V From: Azijn H, et al. Antimicrob Agents Chemother. 2010;54;718-27.

  22. ANTIRETROVIRAL THERAPY Rilpivirine (Edurant)Key Summary Points • Overall has performed equally with Efavirenz • Better tolerated than Efavirenz • Higher virologic failure rate than with Efavirenz-based regimens • Rilpivirine virologic failure often results in cross resistance to Etravirine • Efficacy of Rilpivirine for patients with Efavirenz failure unknown • Co-formulation in development: Tenofovir-Emtricitabine-Rilpivirine

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