1 / 93

Elbasvir-Grazoprevir ( Zepatier )

Elbasvir-Grazoprevir ( Zepatier ). Prepared by : H. Nina Kim, MD MSc and David Spach , MD Last Updated: January 29, 2016. Elbasvir- Grazoprevir ( Zepatier ). Background and Dosing. Elbasvir-Grazoprevir ( Zepatier ). Approval Status - A pproval by United States FDA on January 28, 2016

lsholar
Télécharger la présentation

Elbasvir-Grazoprevir ( Zepatier )

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. Elbasvir-Grazoprevir(Zepatier) Prepared by: H. Nina Kim, MD MSc and David Spach, MD Last Updated: January 29, 2016

  2. Elbasvir-Grazoprevir (Zepatier) Background and Dosing

  3. Elbasvir-Grazoprevir (Zepatier) • Approval Status- Approval by United States FDA on January 28, 2016 • Indications and Usage - Indicated for the treatment of chronic HCV genotypes 1or 4 in adults- Indicated for treatment of patients with HIV coinfection • Class & Mechanism- Elbasvir: HCV NS5A inhibitor- Grazoprevir: HCV NS3/4A inhibitor • Dosing: Elbasvir-Grazoprevir (fixed dose 50 mg/100 mg) One tablet orally once daily, with or without food • Adverse Effects (AE): - Fatigue, headache, and nausea- Increase in ALT > 5x normal in 1% of subjects Source: ZapatierPrescribing Information. Merck & Co., Inc.

  4. Elbasvir-Grazoprevir (Zepatier)Indications and Usage Source: ZapatierPrescribing Information. Merck & Co., Inc.

  5. Elbasvir-Grazoprevir (Zepatier)Drug-Drug Interactions Source: ZapatierPrescribing Information. Merck & Co., Inc.

  6. Elbasvir-Grazoprevir (Zepatier)Drug-Drug Interactions Source: ZapatierPrescribing Information. Merck & Co., Inc.

  7. Clinical Trials Elbasvir-Grazoprevir

  8. Elbasvir-Grazoprevir (EBR-GZR): Summary of Key Studies • Phase 2 Trials- C-SWIFT: EBR-GZR + Sofosbuvir x 8 or 12 weeks in GT 1 or 3- C-WORTHY: EBR-GZR +/- RBV in TN Cirrhotic or null responders- C-WORTHY Coinfection: EBR-GZR +/- RBV in HIV coinfection- C-SALVAGE: EBR-GZR + RBV in PI-experienced patients- C-SCAPE: EBR +/- GZR +/- RBV in GT 2, 4, 5, or 6 without cirrhosis

  9. Elbasvir-Grazoprevir (EBR-GZR): Summary of Key Studies • Phase 3 Trials- C-EDGE TN: EBR-GZR x 12 weeks in treatment-naïve GT 1, 4 or 6- C-EDGE TE: EBR-GZR +/- RBV x 12 or 16 weeks in TE GT 1, 4 or 6- C-EDGE Coinfection: EBR-GZR x 12 weeks in HIV-HCV coinfected- C-EDGE CO-STAR: EBR-GZR x 12 weeks in persons who inject drugs- C-SURFER: EBR-GZR x 12 weeks in GT1 and Chronic kidney disease

  10. Elbasvir-Grazoprevir Treatment-Naïve Patients

  11. Phase 3 TreatmentNaïve Elbasvir-Grazoprevirin Treatment-Naïve HCV Genotype 1, 4 or 6C-EDGE Treatment Naïve (TN) Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.

  12. Elbasvir-Grazoprevirin Treatment-Naïve HCV Genotype 1, 4 or 6C-EDGE TN Study: Features Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.

  13. Elbasvir-Grazoprevir in Treatment-Naïve HCV Genotype 1, 4 or 6C-EDGE TN: Study Design 0 12 16 40 24 28 Week Treatment-naïve GT 1, 4 or 6 (N=421) Elbasvir-Grazoprevir N=316 SVR12 Elbasvir-Grazoprevir Placebo N=105 SVR12 Randomized 3:1 ratio to immediate or deferred arm; stratified by cirrhosis, HCV genotype, subtypeAfter 4 weeks of follow-up, placebo recipients were unblinded and given elbasvir-grazopreviropen label Drug DosingElbasvir-Grazoprevir (50/100 mg): fixed dose combination; one pill once daily Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.

  14. Elbasvir-Grazoprevir in Treatment-Naïve HCV GT 1, 4 or 6C-EDGE TN: Baseline Characteristics Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.

  15. Elbasvir-Grazoprevirin Treatment-Naïve HCV GT 1, 4 or 6C-EDGE TN: Results C-EDGE TN: SVR12 Results by Genotype 299/316 144/157 129/131 18/18 8/10 Primary efficacy analysis included all patients who received ≥1 dose of drug. Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.

  16. Elbasvir-Grazoprevir in Treatment-Naïve HCV GT 1, 4 or 6C-EDGE TN: Results C-EDGE TN: SVR12 by Presence of Cirrhosis or High HCV RNA Level 231/246 68/70 94/94 205/222 Presence of Cirrhosis Baseline HCV RNA Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.

  17. Elbasvir-Grazoprevir in Treatment-Naïve HCV GT 1, 4 or 6C-EDGE TN: Results Baseline NS5A Resistance-Associated Variants and SVR12 in GT1 11/19 133/135 17/18 112/112 *Patients with baseline GT1a RAVs with a ≤5-fold shift to elbasvir: SVR12=90% (9 of 10) *Patients with baseline GT1a RAVs with a >5-fold shift to elbasvir: SVR12=22% (2 of 9) Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.

  18. Elbasvir-Grazoprevir in Treatment-Naïve HCV GT 1, 4 or 6C-EDGE TN: Results Baseline NS3/4A Resistance-Associated Variants and SVR12 in GT1 83/86 58/65 24/25 104/104 Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.

  19. Elbasvir-Grazoprevir in Treatment-Naïve HCV GT 1, 4 or 6C-EDGE TN: Adverse Events § Neither death was considered to be study-related. Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.

  20. Elbasvir-Grazoprevir in Treatment-Naïve HCV GT 1, 4 or 6C-EDGE TN: Conclusions Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.

  21. Phase 2 TreatmentNaïve Elbasvir-Grazoprevir+ Sofosbuvirin Treatment-Naïve HCV Genotype 1 or 3C-SWIFT PoordadF, et al. EASL 2015; Abstract O006.

  22. Elbasvir-Grazoprevir+ Sofosbuvir in Treatment-Naïve GT 1 or 3C-SWIFT Study: Features Source: Poordad F, et al. EASL 2015; Abstract O006.

  23. Elbasvir-Grazoprevir + Sofosbuvir in Treatment-Naïve GT 1 or 3C-SWIFT Study: Study Design for GT 1 8 0 4 6 24 Week n =31 GT-1Non-cirrhotic EBR-GZR + SOF EBR-GZR + SOF n =30 n =20 GT-1Cirrhotic EBR-GZR + SOF EBR-GZR + SOF n =21 Abbreviations: EBR-GZR = elbasvir-grazoprevir; SOF = sofosbuvir Drug DosingElbasvir-grazoprevir(50/100 mg): fixed-dose combination; one pill once dailySofosbuvir: 400 mg once daily Source: Poordad F, et al. EASL 2015; Abstract O006.

  24. Elbasvir-Grazoprevir + Sofosbuvir in Treatment-Naïve GT 1 or 3C-SWIFT Study:Study Design for GT 3 0 8 12 20 24 Week SVR12 N=15 GT-3 Non-cirrhotic EBR-GZR + SOF N=14 SVR12 EBR-GZR + SOF GT-3Cirrhotic N=12 SVR12 EBR-GZR + SOF Abbreviations: EBR-GZR= grazoprevir-elbasvir; SOF = sofosbuvir Drug DosingGrazoprevir/elbasvir (100/50 mg): fixed dose combination; one pill once dailySofosbuvir 400 mg once daily Source: Poordad F, et al. EASL 2015; Abstract O006.

  25. Elbasvir-Grazoprevir + Sofosbuvir in Treatment-Naïve GT 1 or 3C-SWIFT Study: Baseline Characteristics Source: Poordad F, et al. EASL 2015; Abstract O006.

  26. Elbasvir-Grazoprevir + Sofosbuvir in Treatment-Naïve GT 1 or 3C-SWIFT Study: Results for GT 1 C-SWIFT: SVR 12* for GT 1 by Treatment Duration and Cirrhosis 10/30 26/30 16/20 17/18 No Cirrhosis Cirrhosis *Analysis by modified intention-to-treat analysis (excluded patients who discontinued due to reasons other than virologic failure) Source: Poordad F, et al. EASL 2015; Abstract O006.

  27. Elbasvir-Grazoprevir + Sofosbuvir in Treatment-Naïve GT 1 or 3C-SWIFT Study: Results for GT 3 C-SWIFT: SVR 12* for GT 3 by Treatment Duration and Cirrhosis 14/14 10/11 14/15 No Cirrhosis Cirrhosis Analysis by modified intention-to-treat analysis(excluded patients who discontinued due to reasons other than virologic failure) Source: Poordad F, et al. EASL 2015; Abstract O006.

  28. Elbasvir-Grazoprevir + Sofosbuvir in Treatment-Naïve GT 1 or 3C-SWIFT Study: Conclusions Source: Poordad F, et al. EASL 2015; Abstract O006.

  29. Phase 2 TreatmentNaïve Elbasvir + Grazoprevir +/- Ribavirin in Treatment-Naïve HCV GT 2, 4, 5, or 6C-SCAPE Brown A, et al. EASL 2015; Abstract P0771.

  30. Elbasvir + Grazoprevir +/- RBV in Treatment-Naïve GT 2, 4, 5 or 6C-SCAPE Study: Features Source: Brown A, et al. EASL 2015; Abstract P0771.

  31. Elbasvir + Grazoprevir +/- RBV in Treatment-Naïve GT 2, 4, 5 or 6C-SCAPE Study: Study Design for GT 1 24 0 12 Week n =30 GT2Non-cirrhotic EBR-GZR + RBV SVR12 SVR12 GZR + RBV n =30 n =19 SVR12 GT4, 5, or 6Non-cirrhotic EBR-GZR + RBV EBR-GZR n =19 SVR12 Abbreviations: EBR = Elbasvir; GZR = Grazoprevir; RBV = ribavirin Drug DosingElbasvir (50mg)once dailyGrazoprevir (100 mg)once dailyRibavirin (weight-based and divided bid): 800 to 1400 mg/day Source: Brown A, et al. EASL 2015; Abstract P0771.

  32. Elbasvir + Grazoprevir +/- RBV in Treatment-Naïve GT 2, 4, 5 or 6C-SCAPE Study: Baseline Characteristics Source: Brown A, et al. EASL 2015; Abstract P0771.

  33. Elbasvir + Grazoprevir +/- RBV in Treatment-Naïve GT 2, 4, 5 or 6C-SCAPE Study: Results C-SCAPE: SVR12 by Genotype and Regimen EBR + GZR + RBV x 12 weeks EBR + GZR + RBV x 12 weeks GZR + RBV x 12 weeks EBR + GZR x 12 weeks 24/30 19/26 10/10 9/10 4/4 1/4 3/4 3/4 Source: Brown A, et al. EASL 2015; Abstract P0771.

  34. Elbasvir + Grazoprevir +/- RBV in Treatment-Naïve GT 2, 4, 5 or 6C-SCAPE Study: Conclusions Source: Brown A, et al. EASL 2015; Abstract P0771.

  35. Elbasvir-Grazoprevirin Treatment-Experienced Patients

  36. Phase 3 TreatmentExperienced Elbasvir-Grazoprevir+/- Ribavirin in HCV Genotype 1, 4 or 6C-EDGE Treatment Experienced (TE) Kwo P, et al. EASL 2015. Abstract P0886.

  37. Elbasvir-Grazoprevir+/- Ribavirin in HCV Genotype 1, 4 or 6C-EDGE TE Study: Features Source: Kwo P et al. EASL 2015. Abstract P0886.

  38. Elbasvir-Grazoprevir +/- Ribavirin in HCV Genotype 1, 4 or 6C-EDGE TE: Study Design 0 12 16 24 28 36 Week n =105 SVR12 GT1, 4 or 6 Prior Treatment (n = 420) EBR-GZR SVR12 n =104 EBR-GZR + RBV n =105 SVR12 EBR-GZR n =106 SVR12 EBR-GZR + RBV Abbreviations: EBR-GZR = elbasvir-grazoprevir; RBV = ribavirin Drug DosingElbasvir-grazoprevir (50/100 mg): fixed dose combination; one pill once dailyRibavirin (weight-based and divided bid): 800 to 1400 mg/day N =14 Source: Kwo P et al. EASL 2015. Abstract P0886.

  39. Elbasvir-Grazoprevir +/- Ribavirin in HCV Genotype 1, 4 or 6C-EDGE TE: Baseline Characteristics Source: Kwo P et al. EASL 2015. Abstract P0886.

  40. Elbasvir-Grazoprevir +/- Ribavirin in HCV Genotype 1, 4 or 6C-EDGE TE: Results C-EDGE TE: SVR 12* by Treatment Duration and Regimen 97/105 98/104 97/105 103/106 12-Week Regimen 16-Week Regimen * Analysis per protocol: excluding patients who dropped out due to reasons other than virologic failure Source: Kwo P et al. EASL 2015. Abstract P0886.

  41. Elbasvir-Grazoprevir +/- Ribavirin in HCV Genotype 1, 4 or 6C-EDGE TE: Results C-EDGE TE: SVR 12* by Key Subgroups 97/105 98/104 97/105 103/106 * Analysis per protocol: excluding patients who dropped out due to reasons other than virologic failure Source: Kwo P et al. EASL 2015. Abstract P0886.

  42. Elbasvir-Grazoprevir +/- Ribavirin in HCV Genotype 1, 4 or 6C-EDGE TE: Results Source: Kwo P et al. EASL 2015. Abstract P0886.

  43. Phase 2 TreatmentExperienced Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1C-SALVAGE (1) Buti M, et al. Clin Infect Dis. 2016;62:32-6. (2) Forns X, et al. J Hepatol. 2015;63:564-72.

  44. Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1C-SALVAGE Study: Features Source: (1) Buti M, et al. Clin Infect Dis. 2016;62:32-6. (2) Forns X, et al. J Hepatol. 2015;63:564-72.

  45. Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1C-SALVAGE Study: Design 0 12 24 Week PI+PR experienced Genotype 1 Non-cirrhotic (N=45)Cirrhotic (N=34) EBR + GZR + RBV N=79 SVR12 Abbreviations: EBR = elbasvir; GZR = grazoprevir; RBV = ribavirin; PI = protease inhibitor; PR = peginterferon+ribavirin Drug Dosing:Elbasvir: 50 mg once dailyGrazoprevir: 100 mg once dailyRibavirin (weight-based and divided bid): 800 to 1400 mg/day Source: Buti M, et al. Clin Infect Dis. 2016;62:32-6.

  46. Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1C-SALVAGE Study: Participants Source: Forns X, et al. J Hepatol. 2015;63:564-72.

  47. Elbasvir + Grazoprevir+ Ribavirin in PI-experienced HCV GT1C-SALVAGE Study: Results C-SALVAGE: SVR 24* by Baseline Factors 76/79 63/66 33/36 32/34 * Analysis per protocol: excluding patients who dropped out due to reasons other than virologic failureRAVs = resistance-associated variants (at baseline) Source: Buti M, et al. Clin Infect Dis. 2016;62:32-6.

  48. Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1C-SALVAGE Study: Results Source: Buti M, et al. Clin Infect Dis. 2016;62:32-6.

  49. Elbasvir + Grazoprevir+ Ribavirin in PI-experienced HCV GT1C-SALVAGE Study: Adverse Events Source: Forns X, et al. J Hepatol. 2015;63:564-72.

  50. Elbasvir + Grazoprevir+ Ribavirin in PI-experienced HCV GT1C-SALVAGE Study: Conclusions Source: Buti M, et al. Clin Infect Dis. 2016;62:32-6.

More Related