Chronic Hepatitis C and Chronic Hepatitis C and Project ECHOProject ECHO

State of Affairs State of Affairs Spring 2013Spring 2013

Disclosures

• Research funding: – Abbott, Boehringer-Ingelheim, Bristol

Meyers Squibb, Gilead, Idenix, Merck, Roche, Salix, Sundise

• Speaker’s Bureau:– Genentech, Merck, Salix, Vertex

• Consultant:– Kadmon

Hepatitis C Virus InfectionMagnitude of the Problem

• Nearly 4 million persons in United States infected

• Approximately 35,000 new cases yearly• 85% of new cases become chronic• Leading cause of

Chronic liver disease Cirrhosis Liver cancer Liver transplantation

Centers for Disease Control and Prevention. Hepatitis C fact sheet. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm. Accessed February 1, 2006.

Glossary of Terms

• Viral Load- quantity of virus present in blood– Measured by assay of HCV RNA by polymerase chain

reaction (PCR)

• Genotype- different types of HCV virions (think of cousins) identified as 1,2,3,4,5,6– Subtypes (think of siblings)- 1a,1b,2a,2b,3a,3b

• Response to treatment– SVR- Sustained Virologic Response– Relapse and Breakthrough– Nonresponders- partial and null

Hepatitis C VirusGenotypes in the USA

All others1%

Type 310%

Type 217%

Type 172%

McHutchinson JG, et al. N Engl J Med. 1998;339:1485-1492.

Determination of HCV GenotypeINNOLiPA Assay

• HCV genotype

– Best pretreatment predictor of response

– Determines duration of therapy

• All patients should have genotype determined prior to initiating therapy

PCR1a

1b

3a3b

4

2b

2a

5

Illustration by Mitchell L. Shiffman, MD.

Why Treat Chronic Hepatitis C?

• The disease– Common, chronic, and potentially progressive– Complications are becoming more common[1,2]

• Liver failure, HCC

• The treatment– Viral cure, or SVR, is achievable– SVR associated with histologic improvement and gradual

regression of fibrosis[3]

– SVR reduces risk for liver failure and HCC, improves survival[4,5]

1. Kanwal F, et al. Gastroenterology. 2011;140:1182-1188. 2. Shaw JJ, et al. Expert Rev Gastroenterol Hepatol. 2011;5:365-370. 3. Poynard T, et al. Gastroenterology. 2002;122:1303-1313. 4. Craxi A, et al. Clin Liver Dis. 2005;9:329-346. 5. Shiratori Y, et al. Ann Intern Med. 2005;142:105-114.

Milestones in Therapy of Genotype 1 HCV

Adapted from US FDA Antiviral Drugs Advisory Committee Meeting; April 27-28, 2011; Silver Spring, MD.

SV

R (

%)

IFN

6 mos

PegIFN/R

BV

12 mos

IFN

12 mos

IFN/RBV

12 mos

PegIFN

12 mos

2001

1998

2011

Standardinterferon

Ribavirin

Peginterferon

1991

Direct-actingantivirals

PegIFN/RBV/DAA

IFN/RBV

6 mos

616

3442 39

55

70+

0

20

40

60

80

100

Primary Goal of HCV Therapy

• SVR24: undetectable HCV RNA 6 mos after completion of treatment– Considered clinical cure

• Measures of improved outcome– Histologic improvement

• Inflammatory and fibrosis scores

– Portal pressure reduction– Reduction in clinical complications including

HCC– Survival

We Understand the Rules of the Game With IFN-Based Treatment

• Establishing patient candidacy • Assessing potential drug–drug interactions • Evaluating likelihood of SVR in treatment-

naive and treatment-experienced patients • Applying response-guided treatment

algorithms to maximize response and mitigate treatment failure

• Optimally managing adverse events

For Genotype 2 or 3, PegIFN/RBV Remains Standard of Care

• Highly effective therapy with higher cure rates than genotype 1

• 24 wks of therapy is recommended[1,2]

– Some patients (with RVR and low baseline HCV RNA) may be treated for 16 wks if therapy poorly tolerated, although relapse rates may be higher[2]

• Future regimens may offer further improvements, such as – Shorter durations– All-oral therapy – Fewer adverse events

1. Ghany MG, et al. Hepatology. 2011;54:1433-1444. 2. EASL. J Hepatol. 2011;55:245-264.

Two Protease Inhibitors Approved for GT1 HCV Infection Combined With PR

Protease Inhibitor Recommendations Administration

Boceprevir 800 mg TID (every 7-9 hrs)[1,2]

Naive to previous therapy Previous treatment failure Compensated cirrhosis Response-guided therapy Take with food

All patients initiate therapy with 4-wk pegIFN/RBV lead-in phase

After completion of lead-in phase, boceprevir should be added to continued pegIFN/RBV for 24-44 wks

Telaprevir 750 mg TID (every 7-9 hrs)[2,3]

Naive to previous therapy Previous treatment failure Compensated cirrhosis Response-guided therapy Take with food (not low fat)

All patients initiate therapy with 12-wk period of triple therapy with telaprevir plus pegIFN/RBV

Followed by 12-36 wks of pegIFN/RBV

1. Boceprevir [US package insert]. July 2012. 2. Ghany MG, et al. Hepatology. 2011;54:1433-1444.3. Telaprevir [US package insert]. October 2012.

Addition of BOC or TVR to PegIFN/RBV Improves SVR in Genotype 1 Patients

• BOC and TVR each indicated in combination with pegIFN/RBV for genotype 1 HCV patients who are previously untreated or who have failed previous therapy

1. Poordad F, et al. N Engl J Med. 2011;364:1195-1206. 2. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. 3. Bacon BR, et al. N Engl J Med. 2011;364:1207-1217. 4. Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428. 5. Bronowicki JP, et al. EASL 2012. Abstract 11.

0

20

40

60

80

100

SV

R (

%)

Relapsers[3,4] Partial Responders[3,4]

PegIFN + RBV

NullResponders[4,5]

BOC/TVR + pegIFN* + RBV

24-29

7-15

29-40

5

69-83

40-59

63-75

38-44

Treatment Naive[1,2]

*BOC was administered with pegIFN-α2b; TVR was administered with pegIFN-α2a in these trials.

Response Guided Therapy

Patients Responding Early Can Achieve High SVR Rates With Shortened Therapy

Response-guided therapy: patients who achieve optimal virologic response at early time points can receive abbreviated therapy without reducing their chance of SVR

Patients eligible for RGT– Boceprevir: noncirrhotic treatment-naive patients, previous relapsers,

and previous partial responders[1,2]

– RGT criterion: must achieve undetectable HCV RNA at Wk 8 (ie, Wk 4 of triple therapy) and maintain it at Wk 24

– Telaprevir: noncirrhotic treatment-naive patients and previous relapsers*[2,3]

– RGT criterion: must achieve undetectable HCV RNA at Wk 4 of triple therapy and maintain it at Wk 12

– Pts with cirrhosis are not eligible for RGT and should have 48 weeks of therapy

1. Boceprevir [US package insert]. July 2012. 2. Ghany MG, et al. Hepatology. 2011;54:1433-1444. 3. Telaprevir [US package insert]. October 2012.

*AASLD guidelines state that RGT may be considered with TVR in previous partial responders.

RGT Paradigm With BOC + PegIFN/RBV in Tx-Naive Patients

Indicated for all noncirrhotic treatment-naive patients

BOC + PegIFN/RBV

480 28124

PegIFN/RBV

8 3624

Early response stop at Wk 28; f/u 24 wks

HCV RNA Undetectable Undetectable

480 28124

PegIFN/RBVPegIFN/RBV

8 36

BOC + PegIFN/RBV

24

Slow response extend triple therapy to Wk 36; PR to Wk 48; f/u 24 wks

< 100 IU/mL

< 100 IU/mL

Boceprevir [US package insert]. July 2012. Ghany MG, et al. Hepatology. 2011;54:1433-1444. Boceprevir [EU package insert]. July 2012.

HCV RNA

Detectable Undetectable

RGT With TVR + PegIFN/RBV in Tx-Naive Patients and Previous Relapsers

TVR + PegIFN/RBV

480 24124

eRVR stop at Wk 24, f/u 24 wksPegIFN/RBV

TVR + PegIFN/RBV

480 24124

PegIFN/RBV

HCV RNAUndetectable

Undetectable

Detectable (≤ 1000 IU/mL)

Undetectable or detectable (≤ 1000 IU/mL)

No eRVR extend pegIFN/ RBV to Wk 48; f/u 24 wks

HCV RNA

Indicated for all noncirrhotic treatment-naive pts and previous relapsers*[1,3]

1. Telaprevir [US package insert]. October 2012. 2. Ghany MG, et al. Hepatology. 2011;54:1433-1444. 3. Telaprevir [EU package insert]. March 2012.

Undetectable

Undetectable

*AASLD guidelines say RGT “may be considered” for previous partial responders[2] but package inserts recommend 48 wks of therapy.[1,3]

Futility Rules for BOC or TVR + PegIFN/RBV in Tx-Naive and Tx-Exp’d

Pts

All therapy should be discontinued in patients with the following:

1. Boceprevir [US package insert]. July 2012. 2. Ghany MG, et al. Hepatology. 2011;54:1433-1444.3. Telaprevir [US package insert]. October 2012.

*Assay should have a lower limit of HCV RNA quantification of ≤ 25 IU/mL and a limit of HCV RNA detection of approximately 10-15 IU/mL.

Boceprevir[1,2]

Time Point Criteria* Action

Wk 12 HCV RNA ≥ 100 IU/mL Discontinue all therapy

Wk 24 HCV RNA detectable Discontinue all therapy

Telaprevir[2,3]

Time Point Criteria* Action

Wk 4 or 12 HCV RNA > 1000 IU/mL Discontinue all therapy

Wk 24 HCV RNA detectable Discontinue pegIFN/RBV

Adverse Effects

BOC Plus PegIFN alfa-2b/RBV: Adverse Events

• Higher rates of anemia, neutropenia, and dysgeusia in BOC arms vs control

Adverse Event, % PR48 (n = 467)

BOC + PR RGT/48*(n = 1225)

Anemia* 30 50

Neutropenia 19 25

Dysgeusia 16 35*Anemia was managed with RBV reduction and/or epoetin alfa (43% of BOC + PR and 24% of PR).

Boceprevir [US package insert]. July 2012.

TVR Plus PegIFN alfa-2a/RBV: Adverse Events

Higher rates of rash, anemia, and anorectal signs and symptoms in TVR arms vs control

Adverse Event, % PR48 (n = 493)

TVR + PR RGT/48*

(n = 1797)

Rash 34 56

Anemia‡ 17 36

Anorectal events 7 29*Pooled results from TVR arms. †Anemia was managed with RBV dose modification; epoetin alfa was not permitted.

Telaprevir [US package insert]. October 2012.

In most subjects, rash was mild to moderate– Severe rash in 4%; discontinuation due to rash in 6% of

subjects

1. Chen EY, et al. AASLD 2012. Abstract 133. 2. Bichoupan K, et al. AASLD 2012. Abstract 1755.

50

40

30

20

10

0

Pat

ien

ts (

%)

n/N =

18

498 GT1 Patients Evaluated[1]

Started Therapy

2217

1169/407

89/407

43/407

Did Not Start

PatientChoice

Wait forBetter

Therapies

MildDisease

Higher Discontinuation Rates in Real-World Settings Than in Clinical Trials

D/CBeforeWk 12

21

40

30

20

10

0

91/498

D/C TVR < 12 wks

58/174

33[2]

21

36/174

174 GT1 Patients StartedTVR-Based Triple Therapy[2]

Due to AEs

Both BOC and TVR Have Potential for Many Drug–Drug Interactions

• BOC– Strong inhibitor of

CYP3A4/5 – Partly metabolized by

CYP3A4/5– Potential inhibitor of and

substrate for P-gp

• Most drug–drug interactions can be overcome by careful survey of the patient’s medications and judicious substitutions during HCV therapy (or just during the period of PI-based triple therapy)

• TVR– Substrate of CYP3A– Inhibitor of CYP3A– Substrate and

inhibitor of P-gp

Medicines That Are Contraindicated With BOC and TVR

1. Boceprevir [package insert]. July 2012. 2. Telaprevir [package insert]. October 2012.

Drug Class* Contraindicated With BOC[1] Contraindicated With TVR[2]

Alpha 1-adrenoreceptor antagonist

Alfuzosin Alfuzosin

Anticonvulsants Carbamazepine, phenobarbital, phenytoin

N/A

Antimycobacterials Rifampin Rifampin

Antiretrovirals EFV, all RTV-boosted PIs DRV/RTV, FPV/RTV, LPV/RTV

Ergot derivatives Dihydroergotamine, ergonovine, ergotamine, methylergonovine

Dihydroergotamine, ergonovine, ergotamine, methylergonovine

GI motility agents Cisapride Cisapride

Herbal products Hypericum perforatum (St John’s wort) Hypericum perforatum

HMG CoA reductase inhibitors

Lovastatin, simvastatin Lovastatin, simvastatin

Oral contraceptives Drospirenone N/A

Neuroleptic Pimozide Pimozide

PDE5 inhibitor Sildenafil or tadalafil when used for treatment of pulmonary arterial HTN

Sildenafil or tadalafil when used for treatment of pulmonary arterial HTN

Sedatives/hypnotics Triazolam; orally administered midazolam

Orally administered midazolam, triazolam

*Studies of drug–drug interactions incomplete.

Cirrhotic Patients

CUPIC: Interim Analysis of TVR and BOC Use in Cirrhotic Early Access Program

• Interim results of 455 patients presented at 16-20 wks

– Encouraging virologic responses with triple therapy

• ~ 80% treated with TVR-based therapy had undetectable HCV RNA at end of 16 wks of ongoing therapy

• ~ 65% treated with BOC-based therapy had undetectable HCV RNA at Wk 16 of ongoing therapy

– High rate of serious adverse events

• TVR: 48.6%; BOC: 38.4%

– High rate of anemia

• ~ 30% with grade 2 or higher with either drug

– High rate of premature discontinuation

• ~ 25% with either regimen

Hezode C, et al. AASLD 2012. Abstract 51.

Safety Outcome, n (%) TVR-Based Treatment (n = 292)

BOC-Based Treatment(n = 205)

Serious AEs 132 (45.2) 67 (32.7)

Premature discontinuation From serious AEs

66 (22.6)43 (14.7)

54 (26.3)15 (7.3)

Death* 5 (2.6) 1 (0.5)

Infection (grade 3/4) 19 (6.5) 5 (2.4)

RashGrade 3/SCAR 14 (4.8) 0

Hepatic decompensation 6 (2.0) 6 (2.9)

Blood transfusions 47 (16.1) 13 (6.3)

Hezode C, et al. EASL 2012. Abstract 8.

*Causes of death in patients treated with TVR: septicemia, septic shock, pneumopathy, esophageal varices bleeding, endocarditis; causes of death in patients treated with BOC: pneumopathy.

Preliminary Real-World Safety Findings: CUPIC—PIs in Patients With Cirrhosis

Summary

• BOC- or TVR-based triple therapy increases SVR rates over pegIFN/RBV alone for all genotype 1 patient populations that have been evaluated

• On-treatment management techniques including application of RGT algorithms and effective management of adverse events maximize treatment outcomes and mitigate treatment failure

• In spite of significant progress using BOC- or TVR-based triple therapy there are several challenging impediments to universal application for HCV patients

Regimens—Many Challenges

For us—lead-in, response-guided therapy . . .

BOC = 12/dayRBV = 4-7/day

TVR = 6/dayRBV = 4-7/day

Pill Burden Food RequirementFor our patients . . .

Challenges of Current PI-Based Therapy

• Efficacy

– Very dependent on the IFN response

• Tolerability

– Additional AEs beyond pegIFN/RBV

• Regimens

– Complicated (lead-in, RGT)/pill burden

• DDIs

– Many with both agents to common drugs

• Genotype/special populations

– Limited activity in non-GT1, limited data HIV/OLTx, ESRD

Future of HCV Therapy

Dosing and Regimens: Current Challenges and Future Solutions

Challenge Investigational Strategies

Dosing burden: 6-12 pills/day (TID dosing) with

PIs + 4-7 pills/day RBV, food requirements

RGT, lead-in,variable regimen based on

treatment experience,up to 48 wks

Different therapies based on HCV genotype

QD, BID dosing;elimination of RBV;

fixed-dose combinations; no food requirements

No RGT;no pegIFN/RBV lead-in;

shorter regimens

DAA-based regimens effective across genotypes

IFN containing; poor tolerability

IFN sparing, alternative IFNs; agents with fewer adverse

events

Simple Regimen

Short duration, simple, straightforward stopping rules

What Are the Key Elements of an Ideal HCV Regimen?

Pan-Genotypic

Regimen can be used across all genotypes

Highly Effective

High efficacy in traditionally challenging

populations (ie, poor IFN sensitivity, cirrhosis)

Safe and Tolerable

Few or easily manageable adverse

effects

All Oral

PegIFN/RBV replaced with alternate backbone

with low chance of resistance

Easy Dosing

Once daily, low pill burden

HCV Life Cycle and DAA Targets

Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:991-1000.

Receptor bindingand endocytosis

Fusion and

uncoating

Transportand release

(+) RNATranslation

andpolyprotein processing

RNA replication

Virionassembly

Membranousweb

ER lumen

LD

LDER lumen

LD

NS3/4 protease inhibitors

NS5B polymerase inhibitors

Nucleoside/nucleotideNonnucleoside

*Block replication complex formation, assembly

NS5A* inhibitors

Investigational Agents for HCV

Interferons Antiviral agents

Therapeuticvaccines

Hosttarget

Replication, polyprotein processing and/or assembly

Entry

NS5Bpolymerase inhibitors

NS3protease inhibitors

NS5Areplication complex inhibitors

miRNA-122 Cyclophilin

Cyp

inhibitors

Comparison of DAA Profiles

DAA

PI, 1stGeneration

PI, 2ndGeneration

NS5A InhNuc

NS5B InhNonnuc

NS5B Inh

Resistance Profile

Pangenotypic Efficacy

Efficacy

Adverse Events

Drug–DrugInteractions

Good profile Average profile Least favorable profile

Adapted from: Farnik H, et al. Antivir Ther. 2012;17:771-783.

Regimens With 1 DAA + PegIFN alfa/RBV

Regimens With 2 DAAs + PegIFN alfa/RBV

IFN-Free Regimens

Faldaprevir (BI 201335, PI) Daclatasvir (BMS-790052,

NS5A) Sofosbuvir (GS-7977, NI) Simeprevir (TMC-435, PI) Alisporivir (CYP)

Vaniprevir (MK-7009, PI)

Daclatasvir + asunaprevir Sofosbuvir + RBV Sofosbuvir + GS-5885

(NS5A) (FDC) ± RBV Asunaprevir (PI) +

daclatasvir ABT-450 (PI)/RTV/ABT-

267 (NS5A) (FDC) + ABT-333 (NNI) + RBV

Faldaprevir (PI) + BI 207127 (NNI) + RBV

Investigational HCV Regimensin Phase III Clinical Trials

New IFNs

PegIFN lambda-1a + RBV PegIFN lambda-1a +

daclatasvir + RBV PegIFN lambda-1a + RBV +

TVR

ClinicalTrials.gov. November 27, 2012.

Alternative Dosing

TVR BID (approved PI)

On Hold

Daclatasvir Plus Sofosbuvir ± RBV in Treatment-Naive GT1 or 2/3 Patients

• No impact of RBV on viral response

Treatment-naive, noncirrhotic

patients

GT1a or 1b (n = 44)

GT2 or 3 (n = 44)

Daclatasvir + SofosbuvirSofosbuvir

Daclatasvir + Sofosbuvir

Daclatasvir + Sofosbuvir + RBV

Wk 1 Wk 24

Sobosbuvir dosed 400 mg QD. Daclatasvir dosed 60 mg QD. RBV dosed by body weight for GT1 patients (1000-1200 mg/day); 800 mg/day for GT2/3 patients.

Sulkowski MS, et al. AASLD 2012. Abstract LB-2.

GT1

93

100

100

GT2/3

88

100

93

SVR24, %

Treat Now vs Wait: Many Issues to Consider

Treat now•Triple therapy increases SVR•Earlier treatment has higher success rates•Successful treatment may arrest progression of liver disease•Uncertainty about timelines for approval and reimbursement

Defer•First-generation PIs complex, associated with adverse events•Does current treatment failure affect future treatment?•Potential for higher SVR, including in challenging populations•Potential for simpler regimens, QD or BID, fewer adverse effects, eventually IFN-free•Activity in non–genotype 1

Advantages of Future Therapies

• Once-daily dosing• Shorter duration• Simpler regimens—no RGT• Fewer AEs• IFN free• High efficacy

Caveats to Future Therapies

• Very small studies• Potential for toxicity remains

– Agents from multiple classes (nucs, nonnucs, PI, alisporivir) pulled for toxicity

• Efficacy and safety in cirrhosis largely unknown• Minimal data—DDIs, special populations (OLTx, HIV, ESRD)• Timelines uncertain

– Not just approval, but availability and reimbursement

• Costs uncertain, but likely an issue in many regions

HIDING IN PLAIN SIGHT

If this stuff is so good, where are all the patients hiding?

Hepatitis C Virus (HCV) Infection

• HCV is approximately 4 times as prevalent as HIV and HBV in the United States• A 2011 study estimated that as many as 5.2 million persons are living with HCV in

the United States2

HCV=hepatitis C virus; HIV=human immunodeficiency virus; HBV=hepatitis B virus. 1. Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Washington, DC: The National Academies Press; 2010; 2. Chak E, et al. Liver Int. 2011;31(8):1090-101.

Tota

l No.

Infe

cted

(mill

ions

)

DiagnosedUndiagnosed 2.7 to 3.9 Million1

75% Unaware of Infection

1.1 Million1

21% Unaware of Infection~800,000 to 1.4 Million1

65% Unaware of Infection

HIV HBV HCV

4

3

2

1

0

You Are the First Line for HCV Screening

x 2000 patients(average patient load for PCP2)

Average PCP has 40 patients with HCV

in his/her practice2*

2%(US prevalence of HCV1)

One in 30 baby boomers in the US has HCV (3.25%); however certain One in 30 baby boomers in the US has HCV (3.25%); however certain areas have a higher prevalence of the disease.areas have a higher prevalence of the disease.3,43,4

*Across the country HCV prevalence differs by region, state, and locality.ALT=alanine aminotransferase; HCV=hepatitis C virus; PCP=primary care provider; OR=odds ratio.1. Chak E, et al. Liver Int. 2011;31(8):1090-101; 2. Ferrante JM, et al. Fam Med. 2008;40(5):345-351; 3. Smith BD, et al. Abstract #394. Presented at: American Association for the Study of Liver Disease 2011 Annual Meeting; San Francisco, CA; November 5, 2011; 4. Institute of Medicine. Washington, DC: The National Academies Press; 2010.

HCV = hepatitis C virus; HCC = hepatocellular carcinoma. 1. Rustgi VK. J Gastroenterol. 2007;42(7):513-21; 2. Gringeri E, et al. Transplant Proc. 2007;39(6):1901-1903; 3. Sangiovanni A, et al. Hepatology. 2006;43(6):1303-10. 4. The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 243. Presented November 8, 2011. 5. Thein HH, Yi Q, Dore GJ, et al. Hepatology. 2008;48(2):418-31. 6. Missiha SB, et al. Gastroenterology. 2008;134(6):1699–714.

Chronic HCV Infection May Result in Liver Cirrhosis, HCC, and Liver-Related Death

Liver transplant

• HCV is the #1 cause of liver transplant in the United States1

• Up to 45% of patients awaiting liver transplant have HCV2

Liver cancer

• HCV is the leading cause of HCC1

Death

• 4% annual death rate postcirrhosis3

• CDC has identified the number of deaths from HCV now exceed those from HIV4

Fibrosis Cirrhosis Hepatocellular Carcinoma

(with cirrhosis)

The rate of progression of liver fibrosis accelerates as fibrosis advancesand can vary from patient to patient5,6

Year

Nu

mb

er o

f P

atie

nts

1,200,000

1,000,000

800,000

600,000

400,000

0

200,000

1990 2000 2010 2020 2030

25%of patients with HCV

currently have cirrhosis

25%of patients with HCV

currently have cirrhosis

37%of patients with HCV are projected

to develop cirrhosis by 2020, peaking at 1 million

37%of patients with HCV are projected

to develop cirrhosis by 2020, peaking at 1 million

Adapted from Davis GL, et al. Gastroenterology 2010;138:513-21. 1. McGarry LJ. Hepatology. 2012;55(5):1344-55.

Although the Peak of Infections Occurred Decades Ago, Complications From HCV Will Continue to Increase as Chronic HCV Progresses

An estimated 33% of undiagnosed baby boomers with HCV currently have advanced fibrosis (F3-F4, bridging fibrosis to cirrhosis)1

SmokingHCV

Decrease in Life Expectancy With Chronic HCV Is Similar to the Decrease Due to Smoking

HCV=hepatitis C virus.1. Ryder SD. J Hepatol. 2007;47(1):4-6; 2. Centers for Disease Control and Prevention. MMWR. 2002;51:300-303; 3. Centers for Disease Control and Prevention. NVSS. 2010;58(19):1-135.

Lif

e E

xpec

tan

cy (

Yea

rs)

Average30

40

50

60

70

80

90 8 to 12 8 to 12 year year

reductionreduction11

8 to 12 8 to 12 year year

reductionreduction11

13 to 14 13 to 14 year year

reductionreduction22

13 to 14 13 to 14 year year

reductionreduction22

Studies Have Shown a Decreased Rate of Liver Complications in Patients Who Achieved SVR With

Peg-IFN/RBV*

• The HALT-C Trial was a multicenter study of 1145 subjects with advanced chronic HCV who were nonresponders to previous IFN-based treatment

• The trial found that achieving SVR with Peg-IFN/RBV therapy significantly reduced HCV-associated complications and mortality

Rates of Liver-Related Complications (%)

*With pegylated interferon alfa and ribavirin; †Decompensated liver disease included variceal hemorrhage, ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy. HALT-C = Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis; HCC = hepatocellular carcinoma; HCV = hepatitis C virus; IFN = interferon; Peg-IFN = pegylated interferon; RBV = ribavirin; SVR = sustained virologic response. Morgan TR, et al. Hepatology. 2010;52(3):833-44.

Patients With SVR (n=140)

Nonresponders (n=309)

DecompensatedLiver Disease†

LiverTransplantation

HCC Liver-RelatedDeath

13.9%

9.1%11.0%

6.8%

02468

101214161820

1.4% 1.4%0.7% 0.7%

Rat

es (

%)

CDC Guidelines for Screening Baby Boomers

.

The Centers for Disease Control and Prevention (CDC) has created draft guidelines recommending a

one-time anti-HCV antibody test for all baby boomers (those born from 1945 through 1965) in an

effort to identify these undiagnosed individuals

Estimated Prevalence by Age Group2

Num

ber W

ith C

hron

ic H

CV

Infe

ctio

n (m

illio

ns)

Birth Year Group

0

1.6

1.4

1.2

1.0

0.8

0.6

0.4

0.2

1990+1980s1970s1960s1950s1940s1930s1920s<1920

Baby Boomers (Those Born From 1945 Through 1965) Account for 82% of HCV Cases in the United States1

1. Smith BD, et al. Hepatology. 2011; 54(4):554A.2. Adapted from Pyenson B, et al. Consequences of Hepatitis C Virus (HCV): Costs of a baby boomer Epidemic of Liver Disease. New York, NY: Milliman, Inc; May 18, 2009.

http://www.milliman.com/expertise/healthcare/publications/rr/consequences-hepatitis-c-virus-RR05-15-09.php Milliman report was commissioned by Vertex Pharmaceuticals.

$/QALY

Comparison of HCV Cost-Effectiveness With Other Routine Preventive Services

http://www.prevent.org/National-Commission-on-Prevention-Priorities/Rankings-of-Preventive-Services-for-the-US-Population.aspx. Accessed May 23, 2012.Rein DB, et al. Ann Intern Med. 2012;156:263-70

Breast CA,aged 40+

60,000

50,000

40,000

30,000

20,000

10,000

0

$/Q

AL

Y

Colorectal,aged 50+

Flu,aged 50+

Hypertension,aged 18+

HCV testing,1945-1965

HIV testing,aged 13-64

Cholesterolscreening

QALY= quality-adjusted life year.

› According to the National Commission on Prevention Priorities, the cost-effectiveness of HCV testing of baby boomers would be similar to that of hypertension, HIV testing, and cholesterol screening

Summary

• Up to 5.2 million persons are living with HCV in the United States

• 75% of infected individuals are not aware of their HCV status

• HCV is a chronic disease and the number of patients estimated to develop serious liver outcomes is projected to peak in 2020, reaching over 1 million cases of cirrhosis

• HCV can be cured in 75% of those treated with today’s medications

• Special attention should focus on diagnosing and referring populations disproportionately affected by HCV, as recommended by the updated CDC guidelines

– 82% of patients with chronic HCV were born from 1945 through 1965

You are at the front line of screening and TREATMENT—identification is the first step in a patient’s chance for a cure

.

Transition to Care

Project ECHOExtension for Community Health Outcomes

An innovative web-based healthcare delivery system developed to treat chronic and complex diseases in rural and underserved areas

through the use of telemedicine technology.

Terry D. Box, MD Director

Susanne M. Cusick Manager

Objectives

• Enhance the capacity of Community providers to effectively treat common chronic, complex diseases in remote and underserved areas

• Bridge the gap between primary providers and specialist to maximize time and expertise

• Teach and disseminate best practices

• Provide case-based CME to Primary Care clinicians

Objectives-cont.

• Reduce Professional Isolation by providing access to a multidisciplinary specialty care team

• Expand access to care by sharing medical knowledge

• Target Clinical conditions that are common, require complex treatment and have impact on health and economics– Hepatitis C Diabetes Child Psychiatry – Asthma Chronic Pain Rheum. Arthritis

How it Works• Providers are self-identified/recruited to participate

• At each site a lead clinician (MD, NP, PA) is identified to become the local expert

• Site Initiation includes visit from the U of U team to train and assist with tech issues

• Participating providers and staff may visit University to shadow clinicians

How it Works-cont.

• Weekly web-based “Knowledge Network” for disease management

• Providers present cases to ECHO faculty who mentor the local provider

– Proven success: “Outcomes of Treatment for Hepatitis C Virus Infection by Primary Care Providers”

Sanjeev Arora, M.D., Karla Thornton, M.D., Glen Murata, M.D., et al.

N Engl J Med 2011; 364:2199-2207 June 9, 2011

• Real-time, case based learning– CME: Category 1

Capacity and Relationship Building

• Virtual Work Force Multiplier– Efficient and effective delivery of University Faculty expertise and

outreach– Collegial interaction with primary providers

• Expertise is developed in primary providers – who teach co-workers and – serve as local consultants for peers in the clinic/region

Project ECHO HCV- Utah• Launched at the University of Utah in October 2011• Weekly web-based ECHO clinics held

– 29 different sites have participated• (From UT, WY, CO, MT and CA)

– More than 150 consultations on 90+ patients– 18 additional sites awaiting initiation

• Multi-disciplinary ECHO Team present at each clinic: – Hepatologist– Psychiatrist – Pharm D

Project ECHO- Utah

Opportunity for replication in other diseases

-Faculty mentors identified in the following areas

Child and Adolescent Psychiatry Pain Management

Inflammatory Bowel Disease Rheumatoid Arthritis

Cognitive Dysfunction in the Aged Chronic Kidney Disease

Eating Disorders HIV Treatment

Solid Organ Transplant

Project ECHO

Primary Care Providers bringing value driven specialty care to patients and

communities through today’s technology