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
Pre Assessment #1
Pre Assessment #2
Overview
Epidemiology
Pathophysiology
HCV Course
HCV Genotypes
Transmission
Screening
Goals of Treatment SVR = Sustained Virologic Response
Treatment Considerations
Historical Treatment Options
New HCV Treatment Options
HCV Life Cycle
HCV Genome
Sofosbuvir
Sofosbuvir
Potential Drug Interactions
Adverse Effects
Simeprevir
Simeprevir
Adverse Effects
Potential Drug Interactions
Clinical Trials of Note
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)
Ledipasvir/ Sofosbuvir
Ledipasvir
Adverse Effects
Potential Drug Interactions
Clinical Trials of Note Population (n) Duration (weeks) % SVR 12 ION 1 Treatment naïve, +/ cirrhosis (865) 12 97 99 24 98 99 ION 2 Treatment experienced, +/ cirrhosis (440) 12 94 96 24 99 ION 3 Naïve, non cirrhotic (647) 8 93 94 12 95 ION 4 HIV co infected (335) 12 96
Daclatasvir
Daclatasvir
Adverse Effects
Potential Drug Interactions
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=101 90 Genotype 3;tx experienced; n=51 86 Daclatasvir + sofosbuvir x 12 weeks
Ombitasvir, paritaprevir, dasabuvir, ritonavir (3D)
3D
Adverse Effects
Potential Drug Interactions
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=208 92 II Cirrhosis; 3D + riba x 24 weeks; n=172 96
Ribavirin
Ribavirin
Adverse Effects
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
Potential Drug Interactions
Clinical Trials of Note Population (n) % SVR 12 All received sofosbuvir + ribavirin POSITRON Genotypes 2 & 3, tx naïve; 12 weeks. N=207 78 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=190 91 Genotype 3, cirrhosis; 24 weeks. N=60 68
Current Recommendations
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
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
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
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)
Special Populations
HIV Co Infection
Decompensated Cirrhosis
Renal Impairment
Geriatric Patients
Pregnant Patients
Future Options
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 650032) 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 791325) Setrobuvir (ANA598) GS 9669
Grazoprevir/elbasvir
Monitoring
Pre Treatment
During Treatment
Post Treatment
Access to HCV Treatment
Costs and Prior Auths Ombitasvir/paritaprevir/ritonavir $76,653
Rationale for Treatment
Summary
HCV Treatment
Pre Assessment #1
Pre Assessment #2
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