On Target for Hepatitis C Elimination: Direct Acting Antiviral Agents in 2018

Transcription

1 On Target for Hepatitis C Elimination: Direct Acting Antiviral Agents in 2018 Trana Hussaini, PharmD Pharmacotherapy Specialist in Liver Transplantation, VGH Clinical Assistant Professor, Faculty of Pharmaceutical Sciences, UBC

2 Presenter Disclosure Presenter s Name: Trana Hussaini I have no current or past relationships with commercial entities Speaking Fees for current program: I have received no speaker s fee for this learning activity

3 Commercial Support Disclosure This program has received no financial or in-kind support from any commercial or other organization

4 Learning Objectives By the end of this session the audience will be able to: List the currently available direct acting antiviral (DAA) regimens for the treatment of chronic hepatitis C infection Select an appropriate HCV treatment regimen based on a patient's HCV genotype, previous treatment history, renal function and the extent of baseline liver disease

5 % Diagnosed 80% Treated 65% Mortality

6 Global Prevalence of Hepatitis C Hepatology 2015; 61(1):77-87

7 Chronic Hepatitis C Is a Progressive Disease HCC Healthy Liver Hepatic fibrosis Cirrhosis Transplantation 20 to 30 Years Progressive hepatic fibrosis with few or no symptoms over decades Most patients remain asymptomatic until hepatic decompensation Gastroenterol Clin North Am 2015; 44(4): Google Images collage by T. Hussaini Death

8 Global Annual Mortality Globally, 1.34 million people died of hepatitis in 2015 WHO GLOBAL HEPATITIS REPORT,

9 2030 Hepatitis C Elimination is Possible because

10 Treatment Success 100% Evolution of HCV Therapy IFN 6m IFN 12m IFN/R 6m IFN/R 12 m PEG/R 12m PI/PEG/R New DAA Graphics by T. Hussaini

11 HCV Treatment Evolution DAAs PEG-IFN + RBV Sustained Virological Response (SVR)/Cure rates ~ <10% to 55% Prolonged treatment duration ++++ ADR Graphics by T. Hussaini ADR Adverse Drug Reaction; DAAs Direct Acting Antiviral Agents; RBV Ribavirin; PEG-IFN - Pegylated Interferon; SVR Sustained Virological Response

12 HCV Treatment Evolution DAAs PEG-IFN + RBV P/R + Protease Inhibitors (PI) SVR ~40-70% +++++ADR Prolonged treatment duration Genotype 1 only ADR Adverse Drug Reaction; DAAs Direct Acting Antiviral Agents; PEG-IFN - Pegylated Interferon; RBV Ribavirin; SVR Sustained Virological Response

13 HCV Treatment Evolution DAAs PEG-IFN + RBV Interferon Freedom! NS5B + NS5A P/R + Protease Inhibitors (PI) SVR ~90% (GT1) SVR ~40-70% 12 week course +++++ADR ADR Prolonged treatment duration GT3 Genotype 1 only CKD

14 HCV Treatment Evolution DAAs PEG-IFN + RBV NS5B + NS5A P/R + PI 2 SVR ~90% nd Generation DAAs (GT1) SVR ~40-70% SVR > 95% 12 week course Genotype 1 only Pangenotypic ADR Prolonged treatment GT3duration CKD +++++ADR Resistance/TE CKD

15 HCV Treatment Evolution DAAs PEG-IFN + RBV NS5B + NS5A P/R + Protease Inhibitors (PI) 2 SVR ~90% nd Generation (GT1) 3 rd Generation DAAs DAAs SVR ~40-70% SVR > 95% 12 week course SVR > 95% +++++ADR Pangenotypic ADR Pangenotypic Prolonged treatment GT3duration CKD Resistance/TE Genotype 1 only Resistance CKD TE Treatment Experienced

16 Direct-Acting Antiviral Agents C E1 E2 p7 NS2 NS3 NS4A NS4B NS5A NS5B NS3/4A Protease Inhibitor (PI) Multigenotypic to pangenotypic coverage Low barrier to resistance Contraindicated in patients with decompensated cirrhosis (Child-Pugh Class B or C) Moderate to high potential for DDI; less with newer generation PIs NS5B Nucleos(t)ide Inhibitors (NI) BUVIR Pangenotypic coverage Sofosbuvir (2013) High barrier to resistance Renally eliminated -Not recommended in pts with mod-severe renal impairment CrCl < 30ml/min Low potential for DDIs Collage by T Hussaini PREVIR Simeprevir (2013) Paritaprevir/r (2014) Asunaprevir (2016) Grazoprevir (2016) Glecaprevir (2017) Voxilaprevir (2017) NS5A Inhibitors Multigenotypic to pangenotypic coverage Low barrier to resistance Low to moderate potential for DDIs - Acid reducing therapies decrease absorption ASAVIR Ledipasvir (2014) Ombitasvir (2014) Daclatasvir (2015) Elbasvir (2016) Velpatasvir (2016) Pibrentasvir (2017)

17 Factors Determining HCV Treatment Regimen Genotype 1a, 1b, 2, 3, 4, 5, 6 Treatment History Treatment naïve or experienced Treatment Regimen Hepatic Fibrosis Mild to Moderate Fibrosis vs. Cirrhosis Collage by T Hussaini

18 HCV DAA Regimens Regimen Component Classes Dosing Approved Genotypes Sofosbuvir + simeprevir Paritaprevir/RTV/ ombitasvir /dasabuvir Sofosbuvir + daclatasvir Sofosbuvir/ledipasvir Sofosbuvir/velpatasvir Grazoprevir/elbasvir Glecaprevir/pibrentasvir Sofosbuvir/velpatasvir/ voxilaprevir NS5B+ NS3/4A PI NS3/4A PI + NS5A inhibitor + NN-NS5B NS5B+ NS5A inhibitor NS5B+ NS5A inhibitor NS5B+ NS5A inhibitor NS3/4A PI+ NS5A inhibitor NS3/4A PI + NS5A inhibitor NS5B+ NS5A inhibitor + NS3/4A PI Simeprevir: 150 mg QD Sofosbuvir: 400 mg QD Paritaprevir/RTV/ombitas vir: 150/100/25 mg QD Dasabuvir: 250 mg BID Sofosbuvir: 400 mg QD Daclatasvir: 60 mg QD Sofosbuvir/ledipasvir: 400/90 mg QD Sofosbuvir/velpatasvir: 400/100 mg QD Grazoprevir/elbasvir: 100/50 mg QD Glecaprevir/pibrentasvir 300/120mg Sof/Vel/Vox: 400/100/100 mg QD 1, 4 1, 4 (PrO) 1, 3 1, 4, 5, 6 1, 2, 3, 4, 5, 6 1, 4 1, 2, 3, 4, 5, 6 1, 2, 3, 4, 5, 6

19 Ledipasvir(NS5A)/Sofosbuvir(NS5B) HARVONI RBV NS5B NS3 NS5A

20 Ledipasvir/Sofosbuvir Health Canada Approval Oct 2014 Indication - Indicated for the treatment of chronic HCV genotype 1, 4, 5, 6 in adults Not recommended when egfr <30ml/min Dosing: Sofosbuvir-ledipasvir (fixed dose 400 mg/90 mg) one tablet orally once daily, with or without food Adverse Effects (AE): Fatigue, headache Drug Interactions: SOF: P-gp, BCRP substrate - Rifampin, antiepileptics and St John s Wort LVD: P-gp, BCRP substrate & inhibitor. Also weak inhibitor of CYP3A4, 2C9 Acid reducing therapy (PPIs and H 2 blockers decrease exposure to LDV) Ledipasvir/Sofosbuvir [product monograph]. In: e-cps. Ottawa (ON): Canadian Pharmacists Association, 2017

21 Concomitant Drug: Effect Comment Acid Reducing Agents: gastric ph ledipasvir. Ledipasvir/Sofosbuvir Antacids H2-receptor antagonists Proton-pump inhibitors Antiarrhythmics: amiodarone ledipasvir unknown Separate antacid and LDV/SOF administration by 4 hours Administer H2-blockers simultaneously with or 12 hours apart from LDV/SOF at a dose that does not exceed doses comparable to famotidine 40 mg twice daily Proton-pump inhibitor doses comparable to omeprazole 20 mg or lower can be administered simultaneously with LDV/SOF under fasted conditions Coadministration may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. Coadministration of amiodarone with LDV/SOF is not recommended digoxin digoxin Therapeutic concentration monitoring of digoxin is recommended Anticonvulsants: carbamazepine phenytoin phenobarbital oxcarbazepine Antimycobacterials: rifabutin rifampin HMG-CoA Reductase Inhibitors: rosuvastatin ledipasvir sofosbuvir GS ledipasvir sofosbuvir rosuvastatin concentration of ledipasvir and sofosbuvir, leading to reduced therapeutic effect of LDV/SOF. Coadministration is not recommended. Coadministration is not recommended Coadministration of LDV/SOF with rosuvastatin is not recommended Ledipasvir/Sofosbuvir [product monograph]. In: e-cps. Ottawa (ON): Canadian Pharmacists Association, 2017

22 Ledipasvir/Sofosbuvir Clinical Trials SIRIUS # (n=154) GT-1 TE Cirrhotics (P/R ± PI experienced) LDV/SOF + RBV 12 weeks 96% (74/77) LDV/SOF 24 weeks 97% (75/77) *NEJM 2014;370: ; +NEJM 2014;370: ; NEJM 2014;370: ; # Lancet Infect Dis.2015, 15 (4):

23 Current AASLD & IDSA Recommendations for HCV Treatment with Ledipasvir-Sofosbuvir Genotype 1 Patient Populations Treatment naïve with or without cirrhosis* Treatment Duration 8*-12 weeks Treatment experienced** without cirrhosis 12 weeks Treatment experienced** with cirrhosis 24 weeks OR 12 weeks + RBV *Consider treatment duration of 8 weeks in treatment-naïve patients without cirrhosis who have a pretreatment HCV RNA less than 6 million IU/mL **Treatment-experienced patients who have failed treatment with either (a) peginterferon alfa plus ribavirin or (b) HCV protease inhibitor plus peginterferon alfa plus ribavirin Weight based ribavirin dosing: 1000 mg per day for patients less than 75 kg and 1200 mg for those weighing at least 75 kg, divided and administered twice daily. The starting dosage and on-treatment dosage of ribavirin can be decreased based on hemoglobin and creatinine clearance. AASLD-IDSA. Updated 2017 Sep 21.

24 Sofosbuvir(NS5B)/Velpatasvir(NS5A) EPCLUSA Pangenotypic Coverage RBV NS5B NS5A NS3

25 Sofosbuvir/Velpatasvir Health Canada approved Jul 2016 Indication 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 Not indicated in patients with advanced CKD Dosing: Sofosbuvir-Velpatasvir (fixed dose 400 mg/100 mg) one tablet orally once daily, with or without food Adverse Effects (AE): Headache, fatigue, and nausea Drug Interactions: SOF: substrate of BCRP, P-gp VEL: substrate of CYP2B6, CYP2C8 and CYP3A4, BCRP, P-gp, OATP1B1 inhibitor of P-gp, BCRP, OATP 1B1/B3 Sofosbuvir/Velpatasvir [product monograph]. In: e-cps. Ottawa (ON): Canadian Pharmacists Association, 2017

26 Sofosbuvir/Velpatasvir Clinical Trials STUDY PATIENTS REGIMEN SVR12 ASTRAL -1 N= 624 GT 1, 2, 4 6 TN, TE 19% cirrhotic SOF/VEL (N = 629) Placebo (N = 116) 12 weeks 99% ASTRAL -2 GT 2 TN, TE 14% cirrhotic ASTRAL -3 GT 3 TN, TE 29% cirrhotic SOF/VEL (N = 134) SOF/RBV (N = 132) 12 weeks SOF/VEL x 12 weeks (N = 277 ) SOF/RBV x 24 weeks (N = 275) 99% 94% 95% 80% ASTRAL - 4 GT 1 6 TN, TE CTP-B Cirrhosis SOF/VEL X 12 weeks (N= 90) SOF/VEL+RBV X 12 weeks (N = 87) SOF/VEL X 24 weeks (N = 90) 83% 94% 86% Astral-1: Feld JJ et al. NEJM 2015; 373: Astral-2,3: Foster GR et al. NEJM2015; 373: Astral-4: Curry MP et al. NEJM2015; 373:

27 Recommended Dosage Regimens and Durations for Sofosbuvir/Velpatasvir Patient Population Treatment Duration GT 1-6 patients Noncirrhotic or with compensated cirrhosis (Child-Pugh A) SOF/VEL 12 weeks GT 1-6 with decompensated cirrhosis (Child-Pugh B and C) SOF/VEL + RBV* 12 weeks *Weight based ribavirin dosing: 1000 mg per day for patients less than 75 kg and 1200 mg for those weighing at least 75 kg, divided and administered twice daily. The starting dosage and on-treatment dosage of ribavirin can be decreased based on hemoglobin and creatinine clearance. Sofosbuvir/Velpatasvir [product monograph]. In: e-cps. Ottawa (ON): Canadian Pharmacists Association, 2017

28 Grazoprevir(NS3/4A)/Elbasvir(NS5A) ZEPATIER Patients with advanced CKD NS5B NS3 RBV NS5A

29 Grazoprevir/Elbasvir Health Canada Approval Jan 2016 Indication - Indicated for the treatment of chronic HCV genotypes 1 or 4 Contraindicated in patients with decompensated cirrhosis 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 DI: EBR: substrate of CYP3A4 and P-gp - inhibitor of BCRP, P-gp GZR: substrates of CYP3A, OATP1B1/3, BCRP and P-gp - Inhibitor of CYP3A4 & BCRP Grazoprevir/Elbasvir [product monograph]. In: e-cps. Ottawa (ON): Canadian Pharmacists Association, 2017

30 Drug-Drug Interactions: Contraindications Drug Class Drug(s) within Class that are Contraindicated Comments Grazoprevir/Elbasvir Anticonvulsants Antimycobacterials Herbal Products HIV Medications HIV Medications Immunosuppressants Phenytoin Carbamazepine Rifampin St. John s Wort (Hypericum perforatum) Efavirenz Atazanavir Darunavir Lopinavir Saquinavir Tipranavir Cyclosporine Significant decreases in elbasvir and grazoprevir plasma concentrations caused by strong CYP3A induction. Significant decreases in elbasvir and grazoprevir plasma concentrations caused by strong CYP3A induction. Significant decreases in elbasvir and grazoprevir plasma concentrations caused by strong CYP3A induction. Significant decreases in elbasvir and grazoprevir plasma concentrations caused by CYP3A induction. May increase the risk of ALT elevations due to a significant increase in grazoprevir plasma concentrations caused by OATP1B1/3 inhibition. May increase the risk of ALT elevations due to a significant increase in grazoprevir plasma concentrations caused by OATP1B1/3 inhibition. Grazoprevir/Elbasvir [product monograph]. In: e-cps. Ottawa (ON): Canadian Pharmacists Association, 2017

31 Mechanism of Drug Interactions for Grazoprevir/Elbasvir GZR is a substrate of OATP1B drug transporters GZR and EBR are substrates of CYP3A and P-gp OATP1B inhibitors CYP3A or P-gp inducers Strong CYP3A inhibitors GZR EBR GZR EBR GZR Coadministration is contraindicated Coadministration is contraindicated Coadministration is not recommended Zepatier SmPC, Jan Slide Borrowed from Fiona Marra with Permission

32 Grazoprevir-Elbasvir Clinical Trials STUDY PATIENTS REGIMEN SVR12 C-EDGE TN GT 1, 4, 6 TN; 22% cirrhotic C-EDGE TE GT 1, 4, 6 TE; 35% cirrhotic C-SALVAGE GT 1 PI experienced 43% cirrhotics C-WORTHY GT 1 Cohort 1: TN Cirrhotics Cohort 2: TE (null responders) 35% cirrhotics GZR/EBV 12 weeks GZR/EBV ± RBV 12 or 16 WEEKS Single arm GZR/EBV + RBV 12 weeks Overall: 95% GT1a with RAS 58% Overall: 92-97% 96% RAS 91.7% Cirrhosis 94.1% GZR/EBV 12 Wks 97% 18 Wks 94% GZR/EBV + RBV 12 Wks 90% 18 Wks 97% GZR/EBV 12 Wks 91% 18 Wks 97% GZR/EBV + RBV 12 Wks 94% 18 Wks 100% Zeuzem Z, et al. Ann Intern Med 2015;163:1-13. Kwo P et al. EASL Abstract P0886. Lawitz, et al. Lancet 2015 Mar 21; 385(9973): ; Buti et al. Clin Infect Dis. 2016;62(1):32 6.

33 Grazoprevir-Elbasvir: Resistance Associated Substitutions (RAS) HCV GT1a and Impact of Baseline NS5A Polymorphisms on SVR12 NS5A Polymorphism Status EBR-GZR x 12 weeks SVR12% (n/n) EBR-GZR + RBV x 16 weeks SVR12% (n/n) Without baseline NS5A polymorphism (M28, Q30, L31, or Y93) 98% (441/450) 100% (49/49) With baseline NS5A polymorphism (M28*, Q30*, L31*, or Y93*) 70% (39/56) 100% (6/6) Grazoprevir/Elbasvir [product monograph]. In: e-cps. Ottawa (ON): Canadian Pharmacists Association, 2017

34 Recommended Dosage Regimens and Durations for Grazoprevir-Elbasvir Patient Population Treatment Duration Genotype 1a: Treatment-nai ve or P/R experienced without baseline NS5A polymorphisms Genotype 1a: Treatment-nai ve or P/R-experienced with baseline NS5A polymorphisms* Genotype 1b: Treatment-nai ve or P/R-experienced EBR-GZR EBR-GZR + RBV EBR-GZR 12 weeks 16 weeks 12 weeks GT 4: Treatment-naïve EBR-GZR 12 weeks GT 4: PegIFN/RBV-Experienced EBR-GZR + RBV 16 weeks Grazoprevir/Elbasvir [product monograph]. In: e-cps. Ottawa (ON): Canadian Pharmacists Association, 2017

35 Retreatment Options for DDA- Experienced Patients Treating DAA Failures

36 Glecaprevir (NS3/4A)-Pibrentasvir (NS5A) MAVIRET Pangenotypic Coverage Previous DAA failures RBV free NS5B NS5A NS3

37 Glecaprevir-Pibrentasvir Health Canada Approved Aug 2017 Indication - Treatment-naïve patients genotypes 1-6 without cirrhosis and with compensated cirrhosis (Child-Pugh A) - HCV genotype 1 previously treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both Dosing: Three tablets orally once daily, with food (total daily dose of Glecaprevir 300 mg and Pibrentasvir 120 mg) Adverse Effects (AE): most common headache and fatigue Drug Interactions: GLE substrate of CYP 3A4, BCRP, P-gp, OATP1B1/3 Inhibits CYP3A4 (weak), UGT1A1, BCRP, P-gp, OATP1B1/3 PIB substrate of CYP 3A4, BCRP, P-gp Inhibits CYP3A4 (weak), UGT1A1, BCRP, P-gp, OATP1B1/3 Glecaprevir-Pibrentasvir [product monograph]. St-Laurent (QC): Abbvie Corporation, 2017.

38 Hepatology 2017;66(2):389-97; AASLD-IDSA. Updated 2017 Sep 21. Glecaprevir-Pibrentasvir Clinical Trials Study Genotype Treatment History Duration (weeks) N SVR12 Studies in Subjects without Cirrhosis >99% Endurance 1 1 TN + TE % Endurance 2 2 TN + TE >99% % Endurance 3 3 TN % Surveyor 2 Part % 3 TE % 2, 4 6 TN + TE % Surveyor 2 Part TN + TE % Studies in Subjects with Cirrhosis Expedition 1 1,2, 4 6 TN + TE % TN % Surveyor 2 Part 3 3 TE % Studies in Special Populations (with and without cirrhosis) Expedition TN + TE % Magellan 1 Part 2 1, 4 TE-NS5A and/or PI % %

39 SVR12 (%) MAGELLAN-1, PART 2 Randomized trial of Glecaprevir-Pibrentasvir for 12 or 16 weeks in HCV GT1- or GT4- infected patients with prior DAA failure, without cirrhosis or with compensated cirrhosis PI only NS5A only PI + NS5A n N G/P 12 weeks G/P 16 weeks SVR12 rate by prior DAA therapy Hepatology 2017;66(2):

40 Glecaprevir-Pibrentasvir Treatment Regimens Treatment-Naïve Patients HCV Genotype No Cirrhosis Treatment Duration Compensated Cirrhosis (Child-Pugh Class A) Genotype 1,2,3,4,5,6 8 weeks 12 weeks Glecaprevir-Pibrentasvir [product monograph]. St-Laurent (QC): Abbvie Corporation, 2017.

41 Glecaprevir-Pibrentasvir Treatment Regimens Treatment Experienced-Patients HCV Genotype 1, 2, 4, 5, or 6 1 Patients Previously Treated With a Regimen Containing: PEG + RIB +/- sofosbuvir (NS5B inhibitor) An NS5A inhibitor without prior treatment with an NS3/4A protease inhibitor An NS3/4A PI without prior treatment with an NS5A inhibitor No Cirrhosis Treatment Duration Compensated Cirrhosis (Child-Pugh Class A) 8 weeks 12 weeks 16 weeks 12 weeks 3 PEG + RIB +/- sofosbuvir (NS5B inhibitor) 16 weeks Glecaprevir-Pibrentasvir [product monograph]. St-Laurent (QC): Abbvie Corporation, 2017.

42 Sofosbuvir-Velpatasvir-Voxilaprevir VOSEVI Pangenotypic coverage Previous DAA failures RBV free NS5B NS3 NS5A

43 Sofosbuvir-Velpatasvir-Voxilaprevir Health Canada Approved Aug 2017 Indication -adult patients, without cirrhosis or with compensated cirrhosis, genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing an NS5A inhibitor genotype 1, 2, 3, or 4 infection and have been previously treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor Dosing: One tablet (400 mg of sofosbuvir, 100 mg of velpatasvir, and 100 mg of voxilaprevir), taken orally, once daily with food Adverse Effects (AE): most common headache, fatigue, diarrhea, and nausea. Drug Interactions: Similar to Sof/Vel and Vox is a substrate of CYP 3A4, P-gp, BCRP and OATP 1B1/3 Also Inhibitor of P-gp, BCRP and OATP 1B1/3 Sofosbuvir-Velpatasvir-Voxilaprevir [product monograph]. In: e-cps. Ottawa (ON): Canadian Pharmacists Association, 2017

44 Sofosbuvir-Velpatasvir-Voxilaprevir POLARIS Phase 3 Trials in DAA experienced Pts STUDY PATIENTS REGIMEN SVR12 POLARIS-1 N= 415 GT 1 6 NS5A experienced NS5A & NS3 (32%) NS5A & NS5B (61%) NS5A (7%) 46% cirrhotic POLARIS-4 GT 1-4 non-ns5a experienced NS5B & NS3 (25%) NS5B (75%) 46% cirrhotic SOF/VEL/Vox (N = 263) Placebo (N = 152) 12 weeks SOF/VEL/VOX (N = 182) SOF/VEL(N = 151) 12 weeks 96% SOF/VEL/VOX SOF/VEL GT1a 98% 89% GT3 96% 85% N Engl J Med 2017;376:

45 Sofosbuvir-Velpatasvir-Voxilaprevir Treatment Regimens Adults Without Cirrhosis or With Compensated Cirrhosis (Child-Pugh A) HCV Genotype Without Cirrhosis or with Compensated Cirrhosis Patients Previously Treated with an HCV Regimen Containing: Duration Genotype 1,2,3,4,5,6 An NS5A inhibitor 12 weeks Genotype 1,2,3,4* Sofosbuvir without an NS5A inhibitor 12 weeks *US Labeling: indicated for genotype 1a and 3 as comparable SVR12 rates were observed in subjects with genotype 1b and 2 infection treated with Sof/Vel/Vox vs. Sof/Vel. Sofosbuvir-Velpatasvir-Voxilaprevir [product monograph]. In: e-cps. Ottawa (ON): Canadian Pharmacists Association, 2017

46 DAA Regimen Comparison at a Glance... DAA Regimen Genotype Trx Length Previous DAA TE Safety in CKD Safety in CP BC Pharma- Care SOF/VEL 1, 2, 3, 4, 5, 6 12 wks No EBR/GZR 1, 4, wks No GLE/PIB 1, 2, 3, 4, 5, wks Yes SOF/VEL/VOX 1, 2, 3, 4, 5, 6 12 wks Yes CKD: chronic kidney disease; CP BC: Child-Pugh class B or C; TE: treatment experienced; Trx: treatment T. Hussaini

47 Targets for HCV Elimination... Image credit: TUBS. Wikimedia Commons

48 HCV Cascade of Care in British Columbia as of Dec 31, 2012 EBioMedicine 2016; 12: ,906 24%

49 Towards HCV Elimination Scale up screening Target people at high risk of transmission (PWID, MSM, incarcerated) Scale up Treatment by removing treatment barriers Patient level barriers Structural barriers Removing restrictions for disease severity and treatment providers Harm reduction strategies in high risk population Opioid substitution Needle exchange & disposal programs Addiction 2018;113(3):545-63

50

51 AASLD-IDSA. Updated 2017 Sep 21.

52 Check DDIs prior to initiating DAAs!

53 The Future is Promising! Thank you for your attention... Ravidasvir/Sofosbuvir Kollewe J. The Guardian Apr 12. Available from: URL: hepatitis-c-cure-as-effective-as alternative. Image credit: Josep Lago, AFP, Getty Images