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Sofosbuvir-Velpatasvir ( Epclusa )

Sofosbuvir-Velpatasvir ( Epclusa ). Prepared by : H. Nina Kim, MD MSc and David H. Spach , MD Last Updated: August 16, 2017. Sofosbuvir-Velpatasvir ( Epclusa ). Background and Dosing. Sofosbuvir-Velpatasvir ( Epclusa ). Approval Status - A pproval by United States FDA on June 28, 2016

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Sofosbuvir-Velpatasvir ( Epclusa )

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  1. Sofosbuvir-Velpatasvir (Epclusa) Prepared by: H. Nina Kim, MD MSc and David H. Spach, MD Last Updated: August 16, 2017

  2. Sofosbuvir-Velpatasvir (Epclusa) Background and Dosing

  3. Sofosbuvir-Velpatasvir (Epclusa) • Approval Status- Approval by United States FDA on June 28, 2016 • Indications and Usage Indicated for the treatment of chronic HCV genotypes 1-6 in adults:- without cirrhosis or with compensated cirrhosis (Child-Pugh A) - with decompensated cirrhosis (Child-Pugh B and C) combined with ribavirin • Class and Mechanism- Sofosbuvir: HCV NS5B polymerase inhibitor- Velpatasvir: HCV NS5A inhibitor • Preparation: Sofosbuvir-Velpatasvir (fixed dose 400 mg/100 mg) • Dosing:One tablet orally once daily, with or without food • Adverse Effects (AE): Headache and fatigue Source: EpclusaPrescribing Information, Gilead Sciences.

  4. Sofosbuvir-Velpatasvir(Epclusa) Indications and Usage Source: EpclusaPrescribing Information, Gilead Sciences.

  5. Sofosbuvir-Velpatasvir (Epclusa)Estimated Cost of Therapy Source: Gilead Sciences

  6. Phase 3 TreatmentNaïve & Experienced Sofosbuvir-Velpatasvir in HCV Genotype 1, 2, 4, 5, or 6ASTRAL-1 Feld JJ, et al. N Engl J Med. 2015;373:2599-607.

  7. Sofosbuvir-Velpatasvir in HCV Genotype 1, 2, 4, 5, or 6ASTRAL-1: Study Features Source: Feld JJ, et al. N Engl J Med. 2015;373:2599-607.

  8. Sofosbuvir-Velpatasvir in HCV Genotype 1, 2, 4, 5, or 6ASTRAL-1: Study Design 0 12 24 Week Treatment-naïve or experienced GT 1, 2, 4, 5* or 6 (N=740) Sofosbuvir-Velpatasvir N=624 SVR12 Placebo N=116 SVR12 Randomized 5:1 ratio for treatment to placebo. Stratified by cirrhosis and HCV genotype.*Genotype 5 patients (n=6) were assigned to active arm (and not randomized)Placebo recipients were eligible for deferred treatment with sofosbuvir-velpatasvir Drug DosingSofosbuvir-Velpatasvir (400/100 mg): fixed dose combination; one pill once daily Source: Feld JJ, et al. N Engl J Med. 2015;373:2599-607.

  9. Sofosbuvir-Velpatasvir in HCV Genotype 1, 2, 4, 5, or 6ASTRAL-1: Baseline Characteristics Source: Feld JJ, et al. N Engl J Med. 2015;373:2599-607.

  10. Sofosbuvir-Velpatasvir in HCV Genotype 1, 2, 4, 5, or 6ASTRAL-1: Baseline Characteristics Source: Feld JJ, et al. N Engl J Med. 2015;373:2599-607.

  11. Sofosbuvir-Velpatasvir in HCV Genotype 1, 2, 4, 5, or 6ASTRAL-1: Results ASTRAL-1: SVR12 Results by Genotype 618/624 206/210 117/118 104/104 116/116 34/35 41/41 Source: Feld JJ, et al. N Engl J Med. 2015;373:2599-607.

  12. Sofosbuvir-Velpatasvir in HCV Genotype 1, 2, 4, 5, or 6ASTRAL-1: Results ASTRAL-1: SVR12 Results by Genotype 1 Relapse 2 Lost to follow-up 1 Withdrew consent 1 Relapse 1 Death 618/624 206/210 117/118 104/104 116/116 34/35 41/41 Source: Feld JJ, et al. N Engl J Med. 2015;373:2599-607.

  13. Sofosbuvir-Velpatasvir in HCV Genotype 1, 2, 4, 5, or 6ASTRAL-1: Results ASTRAL-1: SVR12 Results by Cirrhosis & Treatment Experience 618/624 496/501 120/121 418/423 200/201 Source: Feld JJ, et al. N Engl J Med. 2015;373:2599-607.

  14. Sofosbuvir-Velpatasvir in HCV Genotype 1, 2, 4, 5, or 6ASTRAL-1: Resistance Baseline NS5A Resistance-Associated Variants and SVR12 Total, n=616 100 100% SVR12 99% SVR12 90 80 70 58% No NS5A RAVs N=359 42% NS5A RAVs N=257 60 SVR12 (%) 50 40 30 20 10 255/257 359/359 0 83/86 58/65 24/25 104/104 Source: Feld JJ, et al. N Engl J Med. 2015;373:2599-607. 14

  15. Sofosbuvir-Velpatasvir in HCV Genotype 1, 2, 4, 5, or 6ASTRAL-1: Adverse Events Source: Feld JJ, et al. N Engl J Med. 2015;373:2599-607.

  16. Sofosbuvir-Velpatasvir in HCV Genotype 1, 2, 4, 5, or 6ASTRAL-1: Conclusion Source: Feld JJ, et al. N Engl J Med. 2015;373:2599-607.

  17. Phase 3 TreatmentNaïve & Experienced Sofosbuvir-Velpatasvir in Genotype 2ASTRAL-2* *Published in tandem with ASTRAL-3 Trial Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  18. Sofosbuvir-Velpatasvir in HCV Genotype 2ASTRAL-2: Study Features Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  19. Sofosbuvir-Velpatasvir in HCV Genotype 2ASTRAL-2: Study Design 0 12 24 Week Treatment-naïve or experienced GT 2 (N=266) Sofosbuvir-Velpatasvir SVR12 N=134 Sofosbuvir + Ribavirin SVR12 N=132 *Randomization stratified by treatment experience and cirrhosis status. Abbreviations: SOF-VEL = sofosbuvir-velpatasvir; RBV = ribavirin Drug DosingSofosbuvir-velpatasvir (400/100 mg): fixed-dose combination; one pill once dailySofosbuvir: 400 mg once dailyRibavirin (weight-based and divided bid): 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  20. Sofosbuvir-Velpatasvir in HCV Genotype 2ASTRAL-2: Baseline Characteristics Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  21. Sofosbuvir-Velpatasvir in HCV Genotype 2ASTRAL-2: Results ASTRAL-2: SVR12 Results 133/134 124/132 P=0.018 for superiority of Sofosbuvir-Velpatasvir compared with Sofosbuvir + Ribavirin Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  22. Sofosbuvir-Velpatasvir in HCV Genotype 2ASTRAL-2: Results ASTRAL-2: SVR12 Results by Cirrhosis & Treatment Experience 99/100 92/96 15/15 14/15 15/15 13/16 4/4 4/4 Treatment Naïve Treatment-Experienced Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  23. Sofosbuvir-Velpatasvir in HCV Genotype 2ASTRAL-2: Adverse Events Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  24. Sofosbuvir-Velpatasvir in HCV Genotype 2ASTRAL-2: Conclusions Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  25. Phase 3 TreatmentNaïve & Experienced Sofosbuvir-Velpatasvir in Genotype 3ASTRAL-3 *Published in tandem with ASTRAL-2 Trial Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  26. Sofosbuvir-Velpatasvir in HCV Genotype 3ASTRAL-3: Study Features Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  27. Sofosbuvir-Velpatasvir in HCV Genotype 3ASTRAL-3: Study Design 0 12 24 36 Week Treatment-naïve or experienced GT 3 (N=552) SOF-VEL N=277 SVR12 SOF + RBV N=275 SVR12 *Randomization stratified by treatment experience and cirrhosis status. Abbreviations: SOF-VEL = sofosbuvir-velpatasvir; RBV = ribavirin Drug DosingSofosbuvir-velpatasvir (400/100 mg): fixed-dose combination; one pill once dailySofosbuvir: 400 mg once dailyRibavirin (weight-based and divided bid): 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  28. Sofosbuvir-Velpatasvir in HCV Genotype 3ASTRAL-3: Baseline Characteristics Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  29. Sofosbuvir-Velpatasvir in HCV Genotype 3ASTRAL-3: Results ASTRAL-3: SVR12 Results 264/277 221/275 264/277 221/275 P<0.001 for superiority of Sofosbuvir-Velpatasvir compared with Sofosbuvir + Ribavirin Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  30. Sofosbuvir-Velpatasvir in HCV Genotype 3ASTRAL-3: Results ASTRAL-3: SVR12 Results by Cirrhosis & Treatment Experience 160/163 141/156 40/43 33/45 31/34 22/31 33/37 22/38 Treatment Naïve Treatment-Experienced Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  31. Sofosbuvir-Velpatasvir in HCV Genotype 3ASTRAL-3: Resistance Baseline NS5A Resistance-Associated Variants and SVR12 Total, n=274 100 97% SVR12 90 88% SVR12 80 84% No BL NS5A RAVs N=231 70 60 16% BLNS5A RAVs N=43 SVR12 (%) 50 40 30 20 10 38/43 225/231 0 • SVR12 was 84% (21/25) in patients with Y93H Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  32. Sofosbuvir-Velpatasvir in HCV Genotype 3ASTRAL-3: Adverse Events Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  33. Sofosbuvir-Velpatasvir in HCV Genotype 3ASTRAL-3: Conclusions Source: Foster GR, et al. N Engl J Med. 2015;373:2608-17.

  34. Phase 3 TreatmentNaïve & Experienced Sofosbuvir-Velpatasvir in Decompensated HCV CirrhosisASTRAL-4 Curry MP, et al. N Engl J Med. 2015;373:2618-28.

  35. Sofosbuvir-Velpatasvir in Decompensated HCV CirrhosisASTRAL-4: Study Features Source: Curry MP, et al. N Engl J Med. 2015;373:2618-28.

  36. Sofosbuvir-Velpatasvir in Decompensated HCV CirrhosisASTRAL-4: Study Design 0 12 36 24 Week Treatment-naïve & experiencedGT 1, 2, 3, 4, 6 CTP Class B SOF-VEL N=90 SVR12 SOF-VEL + RBV SVR12 N=87 SOF-VEL SVR12 N=90 Abbreviations: SOF-VEL = sofosbuvir-velpatasvir; RBV = ribavirin Drug DosingSofosbuvir-velpatasvir (400/100 mg): fixed-dose combination; one pill once dailySofosbuvir: 400 mg once dailyRibavirin (weight-based and divided bid): 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg Source: Curry MP, et al. N Engl J Med. 2015;373:2618-28.

  37. Sofosbuvir-Velpatasvir in Decompensated HCV CirrhosisASTRAL-4: Participants Source: Curry MP, et al. N Engl J Med. 2015;373:2618-28.

  38. Sofosbuvir-Velpatasvir in Decompensated HCV CirrhosisASTRAL-4: Participants Source: Curry MP, et al. N Engl J Med. 2015;373:2618-28.

  39. Sofosbuvir-Velpatasvir in Decompensated HCV CirrhosisASTRAL-4: Results ASTRAL-4: SVR12 Results by Genotype 75/90 82/87 77/90 60/68 65/68 65/71 7/14 11/13 6/12 8/8 6/6 6/7 Source: Curry MP, et al. N Engl J Med. 2015;373:2618-28.

  40. Sofosbuvir-Velpatasvir in Decompensated HCV CirrhosisASTRAL-4: Change in MELD Scores on Treatment 27% Worsened 52% Improved Baseline MELD <15 n=208 n= Change in MELD 84% Improved 8% Worsened Baseline MELD >15 n=26 n= Change in MELD Source: Curry MP, et al. N Engl J Med. 2015;373:2618-28.

  41. Sofosbuvir-Velpatasvir in Decompensated HCV CirrhosisASTRAL-4: Adverse Events Source: Curry MP, et al. N Engl J Med. 2015;373:2618-28.

  42. Sofosbuvir-Velpatasvir in Decompensated HCV CirrhosisASTRAL-4: Conclusions Source: Curry MP, et al. N Engl J Med. 2015;373:2618-28.

  43. Phase 3 HIV Coinfection TreatmentNaïve & Experienced Sofosbuvir-Velpatasvir in HIV-HCV Coinfected PatientsASTRAL-5 WylesD, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

  44. Sofosbuvir-Velpatasvir in HIV-HCV Coinfected PatientsASTRAL-5: Study Features Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

  45. Sofosbuvir-Velpatasvir in HIV-HCV Coinfected PatientsASTRAL-5: Study Design 0 12 24 Week HIV-HCV Coinfected Treatment-naïve & experienced GT 1, 2, 3, 4, or 6 Sofosbuvir-Velpatasvir n =106 SVR12 Drug Dosing: Sofosbuvir-velpatasvir (400/100 mg): fixed-dose combination; one pill once daily Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

  46. Sofosbuvir-Velpatasvir in HIV-HCV Coinfected PatientsASTRAL-5: Participants Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

  47. Sofosbuvir-Velpatasvir in HIV-HCV Coinfected PatientsASTRAL-5: Participants Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

  48. Sofosbuvir-Velpatasvir in HIV-HCV Coinfected PatientsASTRAL-5: Results ASTRAL-5: SVR12 Results by Genotype 101/106 63/66 11/12 11/11 11/12 5/5 Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

  49. Sofosbuvir-Velpatasvir in HIV-HCV Coinfected PatientsASTRAL-5: Results ASTRAL-5: SVR12 Results by Genotype 2 Relapses 1 LTFU 1 LTFU 1 Withdrew Consent 63/66 11/12 11/12 101/106 11/11 5/5 Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

  50. Sofosbuvir-Velpatasvir in HIV-HCV Coinfected PatientsASTRAL-5: Results ASTRAL-5: SVR12 Results by Cirrhosis & Treatment Experience 101/106 71/75 30/31 82/87 19/19 210/218 139/144 42/44 27/28 Treatment Experience Cirrhosis Status Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

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