Management of Chronic HCV 2017 and Beyond Blaire E Burman, MD Virginia Mason Gastroenterology & Hepatology
Relevant Disclosures No financial disclosures to report
Leaning Objectives Burden of HCV Prevalence Incidence Screening Initial Evaluation of HCV Staging Management Therapeutic options Monitoring and follow up 2015 Virginia Mason Medical Center 3
Burden of Chronic Hepatitis C (HCV) Chronic HCV affects over 185 million worldwide Substantial geographic variability United States prevalence estimated at ~3 million Based on most recent NHANES data Accounting for high risk populations, >5 million are HCV-infected 1-2% overall population prevalence Majority infected in 1960s through 1980s 3.5% prevalence among baby boomers
Prevalence of Chronic Active HCV Up to 5 Million Persons Living with Chronic HCV Unware 50% Aware 50% 2015 Virginia Mason Medical Center
HCV: What s the Big Deal? While incidence has declined, rates of more advanced HCV liver disease and associated healthcare costs are rising - WHY? Population most affected is aging Progressive liver disease and co-morbid conditions 2-fold increase in cases of HCV cirrhosis 30% risk of cirrhosis over time 5% risk of hepatic decompensation and ESLD per year Leading indication for liver transplant in the US 3-fold increase in hepatocellular carcinoma HCC is the fastest growing cancer in the US 75% of HCC cases are associated with HCV 3-5% annual risk of HCC once bridging fibrosis established Projected cases of decompensated cirrhosis, liver cancer, and death are projected to continue to increase through 2030
HCV Incidence is Rising Cases of acute HCV tripled between 2010 and 2015 34,000 new cases occurred in 2015 alone Most significant rise among non-hispanic white, rural or suburban persons < age 40 Northwest, Midwest, New England, Appalachian 2-fold rise in maternal infections True scale of rising incidence unknown given vast majority of acute infections are not reported
Improving HCV outcomes and preventing associated morbidity and mortality starts with screening and referral for care
Who should be Screened for HCV? Probably everyone ER based screening Definitely baby boomers Universal 1-time screening of baby boomers has been endorsed by the Centers for Disease Control and Prevention (CDC) and the United States Preventive Services Task Force as of 2013 Definitely patients with risk factors: History of IVDU, incarceration, percutaneous exposure, blood transfusion before 1992, hemodialysis, HIV/HBV 9
HCV Initial Evaluation Establish genotype and baseline viral load Identify disease activity and stage Activity = inflammation Stage = fibrosis Education and counseling Cofactors for fibrosis progression? Alcohol, obesity Rule out viral coinfections, assess immunity and vaccinate for HAV/HBV
FibroScan
Management of Advanced Fibrosis Determine timely treatment plan Screen for complications or cirrhosis and portal HTN Ascites, encephalopathy, varices screening Identify need for transplant evaluation MELD > 18 Initiate HCC surveillance program (stage 3 or 4) Q 6 month imaging Manage cofactors for disease progression Concomitant NASH or ASH, viral co-infections
Benefits of Therapy Halted progression of liver disease Improved synthetic function, prevention of hepatic decompensation Improvement of fibrosis, prevention of cirrhosis Reduced liver and all-cause mortality CAD, DMII Enhanced quality of life Reduction of transmission Including young and active IVDU
HCV Therapy
Basics of HCV Treatment What do I need to know? HCV genotype Baseline HCV viral load Prior treatment experience Cirrhotic or non-cirrhotic if cirrhotic, Child A, B, or C Renal failure Concurrent HBV or HIV Current medication, herb, supplement list
HCV Therapeutic Drug Targets
HCV DAA Pipeline Drug Brand Name Class Genotype Boceprevier Victrelis NS3/4A PI 1 Telaprevir Incevik NS3/4A PI 1 Simeprevir Olysio NS3/4A PI 1 Sofosbuvir Sovaldi Nucleoside NS5B 1-4 Sofosbuvir / Ledipasvir Harvoni NS5B + NS5A 1-4, 6 Paritaprevir/ritonavir/Ombitasvir+Dasabuvir Viekira NS3/4A, NS5A, Non-nuc NS5B 1 Paritaprevir/ritonavir/Ombitasvir Technivie NS3/4A + NS5A 4 Daclatasvir Daklinza NS5A 3 Grazoprevir / Elbasvir Zepatier NS3/4A + NS5A 1,4 Sofosbuvir / Velpatasvir Epclusa NS5B + NS5A 1-6 Sofosbuvir / Velpatasvir / Voxilaprevir Vosevi NS5B+ NS5A + NS3/4A 1-6 Glecaprevir / Pibrentasvir Mavyret NS3/4A + NS5A 1-6
HCV Treatment Options AASLD-IDSA guidelines: www.hcvguidelines.org Treatment options according to genotype, cirrhosis, prior treatment experience (IFN vs DAA) Which regimen? Multiple options patient and payer preference Mavyret Harvoni Viekira Eplclusa Zepatier
New Kids on the Block Glecaprevir / Pibrentastvir (Mavyret) FDA approved August 3 rd 2017 3 tabs once daily with food Approved for all genotypes, treatment naïve and experienced, compensated cirrhosis
Glecaprevir / Pibrentastvir (Mavyret) ENDURANCE-1: 8 vs 12 weeks non-cirrhotic GT1 99.5 vs 100% ENDURANCE-2: 12 weeks vs placebo non-cirrhotic GT2 99% SVR ENDURANCE-3: 8 vs 12 weeks and 12 weeks vs SOF/DCV treatment naïve non-cirrhotic GT3 95% SVR ENDURANCE-4: 12 weeks for non-cirrhotic GT 4-6 99% SVR GT4 (1 drop out), 100% GT5-6
Glecaprevir / Pibrentastvir (Mavyret) EXPEDITION-1: 12 weeks for naïve and experienced pts with GT 1,2,4-6 and compensated cirrhosis 99% SVR; 1 relapse had baseline Y93H mutation EXPEDITION-2: 8-12 weeks for pts with HIV co-infection ± cirrhosis 99% SVR EXPEDITION-4: 12 weeks for pts with GT1-6 and ESRD with CKD stage 4-5 (GFR<30) 98% SVR, safe and well tolerated
Glecaprevir / Pibrentastvir (Mavyret) MAGELLAM-1: 12 weeks ± RBV, Phase 2 trial of noncirrhotic prior DAA failures Low study numbers, 95% SVR, RBV not necessary SURVEYOR 1-3: further eval in cirrhosis
Glecaprevir / Pibrentastvir (Mavyret) Treatment Naïve HCV Genotype Treatment Duration No cirrhosis Child A cirrhosis Genotype 1 8 weeks 12 weeks Genotype 2 8 weeks 12 weeks Genotype 3 8 weeks 12 weeks Genotype 4 8 weeks 12 weeks Genotype 5 8 weeks 12 weeks Genotype 6 8 weeks 12 weeks
Glecaprevir / Pibrentastvir (Mavyret) Treatment Experienced HCV Genotype Previous Regimen Treatment Duration Genotype 1 NS5A without NS3/4A PI NS3/4A PI without NS5A 16 weeks 12 weeks No cirrhosis Child A cirrhosis 16 weeks 12 weeks Genotype 1,2,4-6 PEG/RBV ± SOF 8 weeks 12 weeks Genotype 3 PEG/RBV ± SOF 16 weeks 16 weeks
New Kids on the Block Sofosbuvir / Velpatasvir / Voxilaprevir (Vosevi) Approved July 18 th 2017
Sofosbuvir / Velpatasvir / Voxilaprevir (Vosevi) POLARIS-I: multicenter placebo-controlled phase 3 trial 415 patients with genotype 1-6 and previous NS5A-based therapy failure 41% had compensated cirrhosis 96% overall SVR; 86% for 1a, 95% for 3, and 93% for cirrhosis Baseline RAVs did not affect efficacy
Sofosbuvir / Velpatasvir / Voxilaprevir (Vosevi) POLARIS-4: multicenter phase 3 trial of SOF/VEL/VOX vs SOF/VEL for 12 weeks 333 patients, genotype 1-4, prior DAA failures (but not NS5a) 46% had cirrhosis Overall 98% SOF/VEL/VOX achieved SVR12 vs 90% for SOF/VEL 98% for GT1a, 100% for GT2, 96% GT3, 98% for cirrhosis
Sofosbuvir / Velpatasvir / Voxilaprevir (Vosevi) POLARIS-2: 941 patients with DAA-experienced genotype 1-6 HCV treated for 8 vs 12 weeks Failed to demonstrate lack of non-inferiority POLARIS-3: 219 treatment naïve genotype 3 compensated cirrhotics, 8 and 12 week arms 96% SVR rate for 8 and 12 weeks May be a role for 8 week therapy among treatment naïve, though not currently approved
Cost Wars Fair Pricing?
HCV: Resistance Associated Variants DAA failures had limited options Send resistance testing (HAV RAVs) Add RBV, treat longer Re-treat with Vosevi or Mavyret without resistance testing When is resistance testing necessary? Baseline RAVs didn t make a difference in clinical trials Vosevi not covered treat with SOF/VEL+RBV x 24 weeks
HCV Treatment Monitoring Review med list stop PPIs (if possible), herbs, supplements Routine blood work & HCV viral load at week 4 and week 12 Anticipate mild side effects: 20% rate of fatigue, headache, nausea Repeat viral load 12 weeks after completing therapy = sustained virologic response (SVR) = cure If early stage, no follow up needed HCV antibodies will always be positive; NOT immune to re-infection If cirrhosis: ongoing monitoring, lifelong liver cancer surveillance Its EASY! Expand prescribing to primary care
HCV Therapy Remaining challenges? Difficult to treat and cure populations? End-stage renal disease (non-genotype 1) MAVYRET Resistance-associated variants (RAVs) VOSEVI Decompensated cirrhosis Pre-transplant to treat or not? Active substance abuse Lack of screening and referral Cost of treatment and insurance denials 33
HCV: Cascade of Care 34
City-Wide ER-based HCV Screening Study Baby boomer screening has been sub-optimal EMR based reminders help No need for risk assessment Active PWID (formerly known as IVDU) mostly access healthcare through the ER Rising incidence in this population Higher risk for transmission to others Opt-out testing with reflexive RNA navigator provides follow up appointment within 2 weeks to initiate treatment process Swedish, Harborview, and Virginia Mason
Virginia Mason HCV Treatment Clinic Hepatitis C Treatment Clinic launched 2014 Blaire E Burman, MD, Clinic Director Asma Siddique, MD, Hepatology Alex Kuo, MD, Hepatology Houghton Lee, RN, Hepatology Weekly clinic aiming to provide: Diagnosis, comprehensive evaluation, staging, and liver disease management Focus on patient education and advocacy Timely access to therapy Access to clinical research trials To refer a patient or for more information, call GI/Hepatology at (206) 223-2319
THANK YOU! Blaire.burman@virginiamason.org