THE CHANGING LANDSCAPE OF HEPATITIS INFECTION. Michael E. Herman D.O.

Transcription

1 THE CHANGING LANDSCAPE OF HEPATITIS INFECTION Michael E. Herman D.O.

2 What s New? For Primary Care Providers Importance of diagnosing HCV For HCV Treaters How can we improve current therapies? For everyone What s in the horizon

3 Hepatitis C Infection is CURABLE! We can cure the majority of treated patients 75% of infected individuals have not been diagnosed Largely asymptomatic in first 2-4 decades Most diagnosed patients have not been treated (~75% - 80%) Toxicity of current medications

4 Who is Infected? Moorman AC, et al. JCI 2013;56:40-50 Pyenson B, et al. Milliman Inc, 2009

5 Who Cares? 33% undiagnosed baby-boomers have advanced fibrosis/cirrhosis McGarry LJ, et al. Hepatology 2012;55: Davis G, et al. Gastroenterology. 2010;138(2):

6 USPSTF* Birth Cohort Screening Recommendations One-time screening of ALL adults born between Screening of people at high risk including: Intranasal drug use Current or past IVDU Born to a mother with HCV Incarceration Getting an unregulated tattoo *US Preventive Services Task Force Moyer VA and USPSTF. Ann Intern Med 2013

7 Public Awareness Campaign

8 Benefits of Diagnosis Risk for progression, need for monitoring Lifestyle modifications Alcohol abstinence Risk to others Opportunity for treatment Possible cure Modification of natural history of the disease

9 HCV Cure Improves Prognosis International study, n=530, median age 48, HCV with advanced fibrosis Van der Meer AJ, et al. JAMA 2012;308: SVR = cure

10 HCV Therapy Saves Lives VA Study, n=16,864, all genotypes, all stages. Backus LI et al. Clin Gastroenterolo Hepatol 2011;9:

11 HCV Affects More Than The Liver Natural history study, Japan, n=19,636, HBV (-) patients, aged years Lee MH, et al. JID 2012;206:

12 You Can Make a Difference! Screen and diagnose HCV infection

13 What can we offer today? Triple Therapy 1. Pegylated interferon 2. Ribavirin 3. 1 st Generation protease inhibitor Telaprevir or Boceprevir

14 Can We Improve Current Therapy? Latest research results

15 Predicting the Future

16 What is new in HCV? Small molecules therapy Target specific steps in HCV replication DAA s (Direct Acting Antivirals) Stumbling blocks Resistance Toxicity Drug-drug interactions Cost Combination therapy eventually leading to interferon free regimens

17 The New Terms Protease inhibitors (NS3/4) Polymerase inhibitors (NS5B) Nucleoside Non-nucleoside Palm Thumb Finger NS5A inhibitors Others HCV Genome

18 DAA Profiles Resistance Profile PI 1 st G PI 2 nd G NS5A Nuc NS5B Non-nuc NS5B Pan-genotypic efficacy Potency Adverse Events Good profile Average profile Least favorable profile PI 1 st G: protease inhibitor, first generation PI 2 nd G: portease inhibitor, second generation

19 How Good are These Drugs?

20 Neutrino Trial PegIFN + Sofosbuvir +Ribavirin Naïve G 1, 4, 5 or 6 (81% G1) Open label, no control group US study, n=327 Treatment duration: 12 weeks Three drug regimen Sofosbuvir 400mg once a day (Nuc polymerase inhibitor) Ribavirin usual dose Peginterferon usual dose Lawitz E, et al. N Engl J Med 2013; 368:

21 Neutrino Trial Treatment Naive SVR-12 PegIFN + Sofosbuvir + Ribavirin 12 weeks 100% 80% 60% 40% 20% 90% 89% 96% 100% 295/ /292 27/28 7/7 Cirrhosis: 17% Blacks 17% SVR-12 / subgroups: Genotype 1b: 82% Genotype 1a: 92% Blacks: 87% (n=54) No Cirrhosis: 92% (n=273) Cirrhosis: 80% (n=54) 0% All Genotype 1 Genotype 4 Genotypes 5&6 Lawitz E, et al. N Engl J Med 2013; 368:

22 M.I.A. Sofosbuvir data for genotype 1 prior nonreponders

23 Simeprevir + PegIFN + Ribavirin

24 What can we use? PEG + ribavirin + sofosbuvir Genotypes 1, 4, 5 & 6, naïve Non responders??? 12 weeks, weeks?? Interferon free sofosbuvir + ribavirin Genotypes 2 & 3 PEG + ribavirin + simeprevir Genotype 1, naïve and non-responders 24/48 weeks response guided therapy

25 What is in the pipeline?

26 Interferon-free Regimens

27 Many Unknowns Remain.. FDA approval timeline? Regimen approved? 12, 16, 24, 48 weeks? Payor interference Step up therapy? Restricted access? Excessive copays? Ability to mix and match?

28 My Approach Seize the moment An ideal candidate today may not be ideal in 1-3 years Change in insurance, out of pocket expenses Loss of job Pregnancy, job change New co-morbidities, polypharmacy Progression of liver disease Reality: many patients return in 5-10 years, not 1-2 years

29 How Long Are You Going to Wait? There will always be something better coming down the pipeline.

30 Take Home Points 1. HCV Therapy has taken off 2. We can cure most patients if They are diagnosed They can afford and tolerate the drugs 3. Research is advancing rapidly Interferon-free regimens for G1 are in the future Will some subsets always need interferon? 4. Waiting for the next best thing may not always be better