1. Nancy Reau, MD University of Chicago Chicago, Illinois Mark S. Sulkowski, MD Johns Hopkins University School of Medicine Baltimore, Maryland Clinical Outcomes and Cost–Benefit Considerations in HCV Therapy This activity is supported by an independent educational grant from Gilead Sciences. Image: Roger Harris/Copyright©2014 Science Source. All Rights Reserved

2. clinicaloptions.com/hepatitis Clinical Outcomes and Cost–Benefit Considerations in HCV Therapy About These Slides  Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent.  These slides may not be published or posted online without permission from Clinical Care Options (email: permissions@clinicaloptions.com). Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.

3. clinicaloptions.com/hepatitis Clinical Outcomes and Cost–Benefit Considerations in HCV Therapy Disclosures Nancy Reau, MD, has disclosed that she has received consulting fees from AbbVie, Gilead Sciences, and Idenix. Mark S. Sulkowski, MD, has disclosed that he has received consulting fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and Tobira and has received funds for research support from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and Vertex.

4. clinicaloptions.com/hepatitis Clinical Outcomes and Cost–Benefit Considerations in HCV Therapy *Mortality rates = HBV, HCV, HIV listed as cause of death Because decedent can have multiple causes of death, a record listing more than 1 type of infection was counted for each type of infection Mortality Rates in the US, 1999-2007 Ly KN, et al. Ann Intern Med. 2012;156:271-278. 7 6 5 4 3 2 1 0 19992001 200220032004 2005200620072000 Rate per 100,000 PY* Yr Hepatitis B Hepatitis C HIV

5. clinicaloptions.com/hepatitis Clinical Outcomes and Cost–Benefit Considerations in HCV Therapy SVR Prevents Development of Insulin Resistance P =.007 P =.1 P =.04 Aghemo A, et al. Hepatology. 2012;58:1681-1687. 25 20 15 10 5 0 Rates of de Novo IR (%) OverallHCV GT 1/4HCV GT 2/3 17% 7% 16% 8% 7% 20% 17/23021/1246/7815/9411/1526/30 SVR Non-SVR

6. clinicaloptions.com/hepatitis Clinical Outcomes and Cost–Benefit Considerations in HCV Therapy HCV Viral Replication Associated With Higher All-Cause Mortality Lee MH, et al. J Infect Dis. 2012;206:469-477. All Causes Cumulative Mortality (%) 30.1% 12.8% 12.4% P <.001 for comparison among 3 groups P <.001 for HCV RNA detectable vs undetectable Anti-HCV seropositives, HCV RNA detectable Anti-HCV seropositives, HCV RNA undetectable Anti-HCV seronegatives Follow-up (Yrs) 02468101214161820 35 30 25 20 15 10 5 0

7. clinicaloptions.com/hepatitis Clinical Outcomes and Cost–Benefit Considerations in HCV Therapy Average Annual All-Cause Healthcare Costs Patient PopulationMean Annual All-Cause Healthcare Cost per Person, $ HCV uninfected [1] 9979 HCV positive, noncirrhotic [2] 17,277 HCV positive, compensated cirrhosis [2] 22,752 HCV positive, ESLD [2] 59,995 1. McAdam-Marx C, et al. J Manag Care Pharm. 2011;17:531-546. 2. Gordon SC, et al. Hepatology. 2012;56:1651-1660.

8. clinicaloptions.com/hepatitis Clinical Outcomes and Cost–Benefit Considerations in HCV Therapy HCC Incidence in Cirrhotic Patients: SVR vs No SVR Purevsambuu T, et al. EASL 2014. Abstract O125. 7.7% 15.6% HCC Incidence (%) 0 50 40 30 20 10 0 2468 12141618202224 Time (Yrs) No SVR SVR P =.0009 Median follow-up: 10 yrs

9. clinicaloptions.com/hepatitis Clinical Outcomes and Cost–Benefit Considerations in HCV Therapy Cost–Benefit Considerations With First- Generation Protease Inhibitors  Cost per SVR with TVR or BOC [1,2] –~ $173,000-$189,000 –Increased to ~ $257,000-$332,000 in cirrhotics 1. Bichoupan K, et al. AASLD 2013. Abstract 244. 2. Sethi N, et al. AASLD 2013. Abstract 1847. 3. Di Bisceglie AM, et al. AASLD 2013. Abstract 41. Reproduced with permission. HCV-TARGET study: SVR12, [3] % BoceprevirTelaprevir Treatment Naive (n = 102) Treatment Exp’d (n = 160) Treatment Naive (n = 320) Treatment Exp’d (n = 517) Overall58376159  Noncirrhotics64427364  Cirrhotics39274453

10. clinicaloptions.com/hepatitis Clinical Outcomes and Cost–Benefit Considerations in HCV Therapy Currently, Very Few HCV Patients Are Treated Asrani SK, et al. Curr Gastroenterol Rep. 2014;16:381. 2.7-3.9 million infected 50% HCV detected 32% to 38% referred for care 7% to 11% treated

11. clinicaloptions.com/hepatitis Clinical Outcomes and Cost–Benefit Considerations in HCV Therapy Cost Savings When Most Effective Regimen Selected Estimates (GT 1 IFN ineligible/intolerant) SOF/RBV (24 Wks) SOF/SIM (12 Wks) Cost per regimen, $169,000150,000 SVR rate, %52-8489-100 Base case cost per SVR, $244,000165,000 Hagan LM, et al. Hepatology. 2014;60:37-45.

12. clinicaloptions.com/hepatitis Clinical Outcomes and Cost–Benefit Considerations in HCV Therapy Summary: Selection and Timing of Therapy  Efficacy and safety of regimen should be the key determinants in selecting treatment  Considerations for timing of treatment –Benefits of HCV therapy/cure extend beyond the liver –Public health benefits of cure for eliminating risk of transmission

13. Go Online for Additional Discussion on Cost–Benefit Considerations for HCV CME-Certified Video Downloadable PowerPoint Slideset clinicaloptions.com/costbenefit