A Cure is Within Reach:

Transcription

1 A Cure is Within Reach: A Review of the New HCV Medications Misty Miller, Pharm.D., BCPS, AAHIVP Clinical Assistant Professor University of Oklahoma College of Pharmacy September 11, 2015

2 Pre Assessment #1

3 Pre Assessment #2

4 Overview

5 Epidemiology

6 Pathophysiology

7 HCV Course

8 HCV Genotypes

9 Transmission

10 Screening

11 Goals of Treatment SVR = Sustained Virologic Response

12 Treatment Considerations

13 Historical Treatment Options

14 New HCV Treatment Options

15 HCV Life Cycle

16 HCV Genome

17 Sofosbuvir

18 Sofosbuvir

19 Potential Drug Interactions

20 Adverse Effects

21 Simeprevir

22 Simeprevir

23 Adverse Effects

24 Potential Drug Interactions

25 Clinical Trials of Note

26 COSMOS No to mild fibrosis SIM/SOF/RBV SIM/SOF SIM/SOF/RBV SIM/SOF 12 weeks 24 weeks 96% (26/27) 90% (13/14) 79% (19/24) 93% (14/15) Advanced fibrosis/ cirrhosis 93% (25/27) 94% (13/14) OPTIMIST 1 97% (150/155) OPTIMIST 2 84% (86/103) 93% (28/30) 100% (16/16)

27 Ledipasvir/ Sofosbuvir

28 Ledipasvir

29 Adverse Effects

30 Potential Drug Interactions

31 Clinical Trials of Note Population (n) Duration (weeks) % SVR 12 ION 1 Treatment naïve, +/ cirrhosis (865) ION 2 Treatment experienced, +/ cirrhosis (440) ION 3 Naïve, non cirrhotic (647) ION 4 HIV co infected (335) 12 96

32 Daclatasvir

33 Daclatasvir

34 Adverse Effects

35 Potential Drug Interactions

36 Clinical Trials of Note Population (n) % SVR 12 ALLY1 Advanced cirrhosis, genotypes 1 6; n=60 83 Post liver transplant, genotypes 1 6; n=53 94 Daclatasvir + sofosbuvir + ribavirin x 12 weeks ALLY3 Genotype 3; tx naïve; n= Genotype 3;tx experienced; n=51 86 Daclatasvir + sofosbuvir x 12 weeks

37 Ombitasvir, paritaprevir, dasabuvir, ritonavir (3D)

38

39 3D

40 Adverse Effects

41 Potential Drug Interactions

42 Clinical Trials of Note Population (n) % SVR 12 SAPPHIRE1 Treatment naïve, genotype 1a; 3D +/ riba 97/90 Treatment naïve, genotype 1b; 3D +/ riba 99 TURQUOISE Cirrhosis; 3D + riba x 12 weeks; n= II Cirrhosis; 3D + riba x 24 weeks; n=172 96

43 Ribavirin

44 Ribavirin

45 Adverse Effects

46 Dose Reduction Dose decrease to 600mg Permanently discontinue No cardiac history Hgb < 10 g/dl Hgb < 8.5 g/dl Cardiac history Decrease of 2g/dLin 4 weeks Hgb < 12 g/dl despite dose reduction

47 Potential Drug Interactions

48 Clinical Trials of Note Population (n) % SVR 12 All received sofosbuvir + ribavirin POSITRON Genotypes 2 & 3, tx naïve; 12 weeks. N= FUSION Genotype 2, tx exp; 12 weeks. N=36 86 Genotype 2, tx exp; 16 weeks. N=32 94 Genotype 3; tx exp; 12 weeks. N=64 30 Genotype 3; tx exp; 16 weeeks. N=63 62 VALENCE Genotype 2; 12 weeks. N=73 93 Genotype 3, no cirrhosis; 24 weeks. N= Genotype 3, cirrhosis; 24 weeks. N=60 68

49 Current Recommendations

50 Treatment Eligibility Highest priority High priority Transmission risk Advanced fibrosis or Fibrosis MSM compensated cirrhosis Organ transplant HIV co infection Active IVDU Type 2 3 cryoglobulinemia HBV co infection Incarcerated persons Proteinuria, nephrotic syndrome, glomerulonephritis Debilitating fatigue Type 2 DM Persons on long term hemodialysis Women of childbearing age

51 Genotype 1 No cirrhosis Cirrhosis 1 Daclatasvir + sofosbuvir x 12 Daclatasvir + sofosbuvir x 24 weeks 1 weeks 1,2 1 Ledipasvir/sofosbuvir x 12 weeks LED/SOF x 12 if naïve LED/SOF x 24 weeks if tx exp 1a 3D + ribavirin x 12 weeks 3D + ribavirin x 24 weeks 1b 3D x 12 weeks 3D x 12 weeks 1 Simeprevir + sofosbuvir x 12 Simeprevir + sofosbuvir x 24 weeks 2 weeks 2 1. Class I, Level B (no cirrhosis); Class IIa, Level B (cirrhosis) 2. Addition of ribavirin optional

52 Genotype 2 No cirrhosis Daclatasvir + sofosbuvir x 12 weeks 1 Sofosbuvir + ribavirin x 12 weeks 1. Class IIa, Level B 2. Class IIb, Level C Cirrhosis Daclatasvir + sofosbuvir x 24 weeks 1 Sofosbuvir + ribavirin x 16 weeks 2

53 Genotype 3 No cirrhosis Daclatasvir + sofosbuvir x 12 weeks Cirrhosis Daclatasvir + sofosbuvir x 24 weeks Sofosbuvir + ribavirin + pegylated interferon x 12 weeks Sofosbuvir + ribavirin x 24 weeks (alternative regimen)

54 Special Populations

55 HIV Co Infection

56 Decompensated Cirrhosis

57 Renal Impairment

58 Geriatric Patients

59 Pregnant Patients

60 Future Options

61 Class Approved Investigational NS3/4A inhibitors Simeprevir (TMC 435) Paritaprevir (ABT 450) NS5A inhibitors Ledipasvir (GS 5885) Ombitasvir (ABT 267) Daclatasvir (BMS790052) NS5B inhibitors Faldaprevir (BI201335) Asunaprevir (BMS ) Vaniprevir (MK 7009) Danoprevir (RG 7227) Vedroprevir (GS 9451) Grazoprevir (MK 5172) ABT 493 GS 9857 Elbasvir (MK 8742) Sovaprevir (ACH 1625) Ravidasvir (PPI 668) Samatasvir (IDX 719) ACH 3102 ABT 530 MK 8408 GS 5816 Nucleoside Sofosbuvir (PSI 7851) Mercitabine (RG7128) Valopicitabine (NM283) Balapiravir (R1626) ACH 3422 MK 3682 Non nucleoside Dasabuvir (ABT 333) ABT 072 Beclabuvir (BMS ) Setrobuvir (ANA598) GS 9669

62 Grazoprevir/elbasvir

63 Monitoring

64 Pre Treatment

65 During Treatment

66 Post Treatment

67 Access to HCV Treatment

68 Costs and Prior Auths Ombitasvir/paritaprevir/ritonavir $76,653

69 Rationale for Treatment

70 Summary

71 HCV Treatment

72 Pre Assessment #1

73 Pre Assessment #2

74 A Cure is Within Reach: A Review of the New HCV Medications Misty Miller, Pharm.D., BCPS, AAHIVP Clinical Assistant Professor University of Oklahoma College of Pharmacy September 11, 2015