1 / 22

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.

trella
Download Presentation

Rilpivirine ( Edurant ): A New NNRTI

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related