Hepatitis C Nut and Bolts (2008) - Nevah-Rubin, Ilan

Hepatitis C

Characteristics

RNA virus + sense9.6 Kb in lengthFlaviviridae → hepaciviridae → HCV

HCV HBV HIV

Infected Persons (US) Undiagnosed Persons (US)

HCV, HBV, HIV: Prevalence vs Undiagnosed Cases

* Extrapolated from small population study.

1. American Liver Foundation. Hepatitis C Factsheet. Available at: www.liverfoundation.org. Accessed May 11, 2007.2. NIAID. HIV Infection and AIDS: An Overview. 2005. Available at: www.niaid.nih.gov. Accessed May 14, 2007. 3. Lok A, et al. Hepatology. 2004;39:1-5. 4. Thompson MJ, et al. J Cancer Educ. 2002;17:222-226.

*

3.5 M

2.5 M

1.5 M

.5 M

0

Statistics

• 170 Million infected worldwide

• 2.7-3 Million active infection nationwide

• High medical costs - $600 Million

• 30K New infections/year

• 10K Deaths/year

• Most important causes of Liver Disease

• OLT

HCV Genotypes

• Hepatitis C virus– RNA virus–high mutation

rates– Evolved different genotypes

• 6 known genotypes– Genotype 1 (75%)– Genotype 2 (10%)– Genotype 3 (10%)

• The above 3 are the most common in the United States

• Little difference in mode of transmission or natural history of infection among different genotypes

Flamm SL. JAMA. 2003;289:2413-2417.

Distribution of HCV Genotypes

75%

10%

10%

5%

Genotype 1

Genotype 2

Genotype 3

Other

Alcoholics~240,000

(11%–36%)5

HIV-infected ~300,000

(30%)4

Living below poverty level ~940,000(2.4%)6

Prevalence of HCVin Select Populations

Incarcerated ~330,000 to 860,000

(16%–41%)1

Veterans ~280,000 (8%)8

IDU~300,000

(80%–90%)2,3Homeless

~175,000 (22%)7

Children(6–18 years old) ~100,000 (.1%)9

Adapted from the following:

1. CDC. MMWR. 2003;52(RR-1):1-33. 2. Edlin B. Hepatol. 2002;36(5 suppl 1):S210-219. 3. NHSDA Report 2003. 4. Poles M, et al. Clin Infect Dis. 2000;31:154-161. 5. LaBrecque D, et al: Hepatitis C Choices. 2002:7-15. 6. Alter M, et al. N Engl J Med. 1999;341:556-562. 7. Nyamathi A, et al. J Gen Intern Med. 2002;17:134-143. 8. Bräu N, et al. Am J Gastroenterol. 2002;97:2071-2078. 9. Jonas M. Hepatol. 2002;36(5 suppl 1):S173-S178. 10. Armstrong GL, et al. Ann Intern Med. 2006;144:705-714.

Male (63%)

Female (37%)

Hepatitis C Virus Infection Prevalence by Age

0

1.0

2.0

3.0

4.0

5.0

< 11 11-19 20-29 30-39 40-49 50-59 60-69 ≥ 70

Age Group

An

ti-H

CV

Po

siti

ve (

%)

Alter MJ, et al. N Eng J Med. 1999;341:556-562.

HCV replication and infection

Adapted from Pawlotsky JM, Gish RG. Antivir Ther 2006;11:397-408

Hepatitis C VirusFate of Acute Infection

15%

Chronic85%

Spontaneousresolution

Alter MJ, et al. N Eng J Med. 1999;341:556-562.

Natural History

Hepatitis C Virus InfectionNatural History

Stable80% (68%)

HCCLiver failure25% (4%)

Slowlyprogressive75% (13%)

Resolved15% (15%)

Acute HCV

Cirrhosis20% (17%)

Chronic HCV85% (85%)

ETOH

HIV

Fe

Hepatic

viruses

Hepatitis C Virus InfectionPopulation at Risk

– Ever injected illegal drugs / intranasal cocaine use– Tattoo and Body piercing – Received clotting factors made before 1987 – Received blood/organs before July 1992 – Ever on chronic hemodialysis – Evidence of liver disease – Incarceration– Healthcare, emergency, public safety workers

after needle stick/mucosal exposures to HCV-positive blood

– Children born to HCV-positive women Centers for Disease www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm Control and Prevention. Hepatitis C fact sheet.

Testing Strategies for HCV

RF for HCVand/or Abn LFT’s

Anti HCV (EIA) testing

< 5% Chance of HCV

Prior exposure to HCV

HCV VL + Genotype

RIBA

NO HCV Exposed + Cleared

Refer forevaluation and Tx.

NO HCVHCV

VL + Genotype

positivenegative

Hepatitis C VirusDiagnostic Testing

Diagnostic Test Type

Specifications Serologic VirologicMode of detection Antibodies Virus

Sensitivity > 95% > 98%

Specificity Variable > 98%

Detection postexposure

2-6 months 2-6 weeks

Use Screening Confirmation

• False positives– Autoimmune disorders– Spontaneous resolution of viral infection

• False negatives– Chronically immune suppressed– Transplant recipients– Chronic renal failure on dialysis– HIV positive

HCV Antibody TestingLimitations

Physical Exam

• Non Specific (Malaise / Weakness)

• Chronic liver disease

Palmar Erythema Temporal Wasting

Gynecomastia Spider Angiomas

Caput Medussa Dupuytren’s contracture

Clubbing Asterixis

Icterus Enlarged Parotid

Testicular atrophy HSM

Extrahepatic Manifestations

• Autoimmune / Rheumatological– Mixed Cryoglobulinemia, Sjögren and Arthritis

• Hematological– NHL

• Endocrinological– Thyroid and DM

• Dermatological– PTC and Lichen Planus

Laboratory Evaluation

• CBC

• BMP

• LFT’s

• TFT’s

• HIV

• Viral Hepatitis

• Genotype

• Viral Load

• Liver Biopsy

• A1C

• Hemochromatosis

(Fe Studies)

• A1-AT

• Wilson’s Dz

• Autoimmune

– ANA, RF, AMA

Hepatitis C Virus InfectionLiver Biopsy

• Only test that can accurately assess– Severity of inflammation– Degree of fibrosis

• Determines the following– Risk for developing cirrhosis in future– Need for therapy– Need for ongoing therapy when initial

treatment has failed

Liver Biopsy (Metavir)

Who to treat?

Innocent until proven guiltyTreatment until proven otherwise

Who to treat?

• Age 18

• Liver Enzyme elevation

• Liver Biopsy (Stage dependant ?)

• Compensated Liver Disease (Tbili, INR,

Alb, Plt, HE, Ascites)

• Hematologic parameters (Hb, WBC, Cr)

• Controlled depression

Who NOT to treat?

• Major/Uncontrolled depressive disorder

• Renal/Lung/Heart Transplant

• Autoimmune Hepatitis

• Uncontrolled hyperthyroidism

• Pregnant – Unwilling to go contraception

• Age under 3

• Hypersensitivity

• Severe Disease: HTN, CHF, CAD, DM, COPD

Goals of Treatment

• Sustained Virological

Response

• Prevent the progression of

Cirrhosis

• Reduce Risk of HCC

Factors Associated With SVRPretreatment or fixed• Genotype• HCV RNA level• Histology• Race• HIV coinfection• Steatosis / IR?• Body weight• Adherence

Dynamic factors• Rapid virologic

response (HCV RNA negative at Wk 4)

• Early virologic response– Partial (HCV RNA decline of

> 2 logs at Wk 12)– Complete (HCV RNA

negative at Wk 12)

SVR in Patients Who Achieved an RVR

90 282 257 9

GT 1 GT 2 GT 3 GT 4

100

868688

Patients With an RVR

RVR: HCV RNA negative (< 50 IU/mL) at Wk 4

Fried MW, et al. EASL 2008. Abstract 7.

0

20

40

60

80

100

SV

R (

%)

n =

Calculating a Cure: Pretreatment Characteristics

• Likelihood of SVR depends on interactions of multiple factors

• Can individual probabilities of SVR be estimated?

• Data from 2 registration trials of pegIFN-2a + RBV used to identify important factors related to SVR

• Modeling used to vary important baseline characteristics

Foster GR, et al. Scand J Gastroenterol. 2007;42:247-255.

Everyone Is Special

Pro

bab

ility

of

Ach

ievi

ng

an

SV

R

100

80

60

40

20

0Patients Number 1 2 3 4 5 6 7 8

9789

74

52

36

19 147

Cirrhosis No No No No No No No Yes

ALT quotient 7 2 2 2 2 2 1 1

Age in years 20 20 43 43 43 60 60 60

BMI 20 20 26 26 26 30 30 30

HCV RNA, IU/mL x 103 40 40 40 1200 9000 9000 9000 9000

Foster GR, et al. Prediction of sustained virological response in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) and ribavirin.

Scandinavian Journal of Gastroenterology. 2007;42(2):247-255.

VS.

Pegasys 180 mcg/week

Copegus 1000 / 1200 mg/day

(75kg)

PEG-intron 1.5 mcg/Kg/week

Rebetol 1000 / 1200 mg/day

(75kg)

Genotype 1/4

VS.

Pegasys 180 mcg/week

Copegus 800 mg/day

PEG-intron 1.5 mcg/Kg/week

Rebetol 800 mg/day

Genotype 2/3

Current Therapy of Hepatitis C

Based on HCV genotype

• Genotype 148 weeks

PEG IFN alpha 2a 180 ug per week andRBV 1000-1200mg per day ORPEG IFN alpha 2b 1.5ug/kg per week andRibavirin 800-1400mg/day

• Genotype 2 or 324 weeks

PEG IFN alpha 2a or 2b andRibavirin 800mg/day

Definition: Viral Responses• Sustained Virological Response (SVR)

• End of Treatment Response (ETR)

• Non-Responders (NR)– Breakthrough and Null responders

• Relapser (R)

• Rapid Virological Response (RVR) – 4wk

• Early Virologcal Response (EVR) – 12wk– cEVR

– pEVR

RVR

cEVRpEVR

4 12 24 48 72

NR

BT

ETR SVR

Rel>2log ↓

Undetectable HCV RNA <50IU/ml

Definition: Viral Responses

Efficacy of current HCV combination therapy by genotype

1. Hadziyannis SJ, et al. Ann Intern Med 2004;140:346-355;2. Fried MW, et al. N Engl J Med 2002;347:975-982;3. Manns MP, et al. Lancet 2001;358:958-965;4. Zeuzem S, et al. J Hepatol 2004;40:993-999

12 or 3

42–52% response rate1–3

Genotype

76–93% response rate1–4

Current Therapy of Hep CTreat Algorithm

Stop therapyNon responder

< 2 log drop

Virus positive

Virus presentNon responder

Virus negativeSVR

Virus presentRelapser

Check viral Load 24 weeks after therapy

Virus negativeET Responder

End of Treatment Viral Load

Treat till 48 weeks

Virus negative

Treat till week 24Check Viral Load again

> 2 log drop but virus positive virus negative

Viral Load at week12

Genotype 1

Treat for 24 weeks

Genotype 2 or 3

Start Therapy

?

Ferenci P, et al. J Hepatol. 2005;43:425.

Pa

tie

nts

wit

h S

VR

(%

)

HCV RNA StatusWeek 4 Negative ≥2 log <2 log ≥2 log <2 log Week 12 Negative Negative Negative ≥2 log ≥2 log Week 24 Negative Negative Negative Negative Negative

PEG IFN -2a 180 mg+ RBV 1000–1200 mg

91

72

60

4843

0

20

40

60

80

100

*Negative predictive value = 74%; positive predictive value = 75%.*Negative predictive value = 74%; positive predictive value = 75%.

Rapid Virologic Response (RVR)

91 90 90 90

65

ETR

SVR

RBV dose(mg/day) =

Berg800

Sanchez-Tapias800

Ferenci1000-1200

33

16

31

46 44

77

0

20

40

60

80

100

SV

R (

%)

Slow-to-Respond Patients: Extending Therapy

Berg T, et al. Gastroenterology. 2006;130:1086-1097. Sanchez-Tapias JM, et al. Gastroenterology. 2006;131:451-460. Ferenci P, et al. AASLD 2006. Abstract 390.

72 weeks48 weeks

Pearlman BL, et al. Hepatology. 2007;46:1688-1694.

SVR rate 72 wks treatment in G1 pts with pEVR

• PegIFN alfa-2b 1.5 µg/kg/wk + RBV 800-1400 mg/day

• HCV RNA positive at Wk 12 but HCV RNA negative at Wk 24 (N = 101 slow responders)

• Continued treatment through 48 vs 72 wks

• Baseline characteristics– 48% black

– 78% high HCV RNA

– 26% F3/4 fibrosis

– 34% BMI > 30

– 18% high fasting glucose

SVR rate 72 wks treatment in G1 pts with pEVR

Response, % 48 Wks 72 Wks P Value

EOT 45 48 NS

SVR 18 38 .03

Relapse 59 20 .004

Treatment cessation

14 15 NS

Pearlman BL, et al. Hepatology. 2007;46:1688-1694.

Shiffman ML, et al. N Engl J Med. 2007;357:124-134.

Patients infected with HCV genotype 2/3

(N = 1291)

RVR: yes67%

(871 / 1291)

SVR

378/461 370/410

55/205 105/215

0%

20%

40%

60%

80%

100%

0%

20%

40%

60%

80%

100%

SVR

ACCELERATE Trial: SVR G2/3 Pts With and Without an RVR

82%

27% 49%

90%

16 wks24 wks

16 wks24 wks

RVR: no33%

(420 / 1291)

Reddy KR, et al. AASLD 2005. Abstract 596.

Influence of Cumulative RBV: Wks 1-12 on SVR in G1

Cumulative RBV Exposure (Wks 1-12)

SV

R (

%)

0

20

40

100

6657

62

45

425

< 60%60% to 79%80% to 96%≥ 97% Total

80

60

n = 325 56 44 0

*HCV RNA–negative (< 50 IU/L) patients at Week 24 randomized to continue treatment with/without RBV at Week 26.

Bronowicki J, et al. Gastroenterology. 2006;131:1040-1048.

PegIFN alfa-2a 180 µg/wk + RBV 800 mg/day

(n = 173)PegIFN alfa-2a 180 g/wk

+ RBV 800 mg/day(N = 516)

PegIFN alfa-2a 180 µg/wk(n = 176)

Week 26

Follow-up

Discontinuing RBV on G1 Patients Responding to Therapy

Week 24: HCV RNA negative*

Week 48 Week 72

Discontinuing RBV oif n Patients Responding to Therapy:

SVR

Bronowicki J, et al. Gastroenterology. 2006;131:1040-1048.

Outcome %

Treatment During Last 24 Wks

P ValuePegIFN alfa-2a + RBV

(n = 173)

PegIFN alfa-2a

(n = 176)

SVR (ITT) 68.2 52.6 .004

SVR (PP) 71.5 56.7 .006

Complication / Side Effect

• PEG-Interferon alfa 2 a/b– Flu-like symptoms– Depression / Mood instability– Cytopenias (WBC / Plt)– Thyroid (hypo / hyper)– Alopecia – Nausea / Vomiting /Abdominal pain

• Ribavirin– Hemolytic anemia– Rash

Non-Responder / Relapser

• New Molecules (STAT-C)

• Clinical Trials

• Retreatment with different PEG molecule

• Infergen (Consensus IFN)?

• Induction Therapy?

Future Therapies

• Viral Entry Inhibitors– HC Ig. and Monoclonal Ab.

• HCV RNA Translation Inh.

• Post Translational Processing Inh.– NS3-4A Serine Proteinase Inh.

• HCV Replication Inhibitors– NS5B Polymerase Inh, Cyclophilin B Inh,

NS5A Inh, Helicase Inh

• Virus Assembly and Release Inh

Targets for New Treatments

1) Virus Entry

2) Uncoating

3) Protein Synthesis

4) Cleavage

5) RNA Replication

6) Packaging

7) Maturation

8) Re-infection

Adapted from: Pawlotsky JM, Gish RG. Future therapies for Hepatitis C. Antivir Ther. 2006;11:397-408.

• Randomized, placebo-controlled, phase II trial

TVR + PegIFN alfa-2a + RBV(n = 79)

PegIFN alfa-2a + RBV

TVR + PegIFN alfa-2a + RBV(n = 79)

TVR + PegIFN alfa-2a + RBV(n = 17)

PegIFN alfa-2a + RBV

Treatment-naive patients infected

with HCV genotype 1*

(N = 250)

Week 12

*Patients received TVR 1250-mg loading dose followed by 750 mg every 8 hrs or placebo based on the arm to which they were randomized. †Patients must achieve undetectable HCV RNA at Week 4 (< 10 IU/mL) and at last test before stopping therapy at 12 or 24 weeks.

Week 24 Week 48

24-week†

follow-up

PROVE 1: Telaprevir + PegIFN/RBV in Naive HCV GT1

24-week†

follow-up

Placebo + PegIFN alfa-2a 180 g/wk + RBV 1000/1200 mg QD(n = 75)

EOT

EOT

SVR

SVR

McHutchison J, et al. EASL 2008. Abstract 4.

PROVE 1: Response Rates (ITT)

Treatment, % Week 4 Undetectable*

Week 12 Undetectable*

SVRRelapse

(n/N)§

PegIFN/RBV/placebo 48 wks (n= 75)

11 45 41 23 (8/35)

TVR/PegIFN/RBV 12 wks pegIFN/RBV 36 wks (n = 79)

81 80 67† 6 (3/51)

TVR/pegIFN/RBV 12 wks pegIFN/RBV 12 wks¶ (n = 79)

81 68 61‡ 2 (1/41)

TVR/pegIFN/RBV 12 wks¶ (n = 17)

59 71 35 33 (3/9)

*HCV RNA < 10 IU/mL.†P = .001 vs pegIFN/RBV/placebo 48 weeks. ‡ P = .02 vs pegIFN/RBV/placebo 48 weeks. ¶Only subjects who met the RVR criterion and stopped at 12 or 24 total weeks of treatment.§Relapse denominator is the number of subjects with undetectable HCV RNA at completion of assigned treatment duration.

McHutchison J, et al. EASL 2008. Abstract 4.

PROVE 1: AEs Associated With TVR

• Gastrointestinal events, skin events (rash, pruritus), and anemia more frequent in TVR treatment arms – Moderate and severe rash more frequent in TVR-based

treatment arms

– Incidence and severity of other AEs similar to peginterferon alfa-2a and ribavirin alone

• Cumulative discontinuation due to AEs by Week 12 – TVR treatment arms: 18%

– Peginterferon alfa-2a and ribavirin only: 4%

• Hemoglobin levels lower in TVR arms for first 12 weeks

McHutchison J, et al. EASL 2008. Abstract 4.

Treatment-naive patients

infected with HCV

genotype 1*

(N = 323)

TVR + PegIFN alfa-2a + RBV(n = 81)

TVR + PegIFN alfa-2a + RBV(n = 82)

TVR + PegIFN alfa-2a(n = 78)

Week 12

*Patients received TVR 1250-mg loading dose followed by 750 mg every 8 hrs or placebo based on the arm to which they were randomized. Patients received 12 or 24 weeks regardless of whether RVR occurred.

Week 24 Week 48

PROVE 2: TVR + PegIFN ± RBV in HCV G1 Naive Patients

Placebo + PegIFN alfa-2a 180 µg/wk + RBV 1000-1200 mg QD(n = 82)

PegIFN alfa-2a + RBV(n = 81)

Week 36

Follow-up

Follow-up

Follow-up

Dusheiko G, et al. EASL 2008. Abstract 58.

PROVE 2: Response Rates (ITT)

Treatment, %Week 4

Undetectable*

Week 12 Undetectable

* SVR¶ Relapse

(n/N)§

PegIFN/RBV/placebo 48 wks (n = 82)

12 41 48 20 (9/45)

TVR/pegIFN/RBV 12 wks pegIFN/RBV 12 wks (n = 81)

69† 73† 68‡ 14 (8/56)

TVR/pegIFN/RBV 12 wks (n = 82)

80† 79† 62¥ 29 (18/63)

TVR/pegIFN 12 wks (n = 78)

51 62 36 48 (22/46)

Dusheiko G, et al. EASL 2008. Abstract 58.

PROVE 2: Adverse Events• Skin events (rash, pruritus) more frequent in TVR treatment

arms – Rash most common reason for treatment discontinuation in TVR/pegIFN/RBV

treatment arms: 7% (12 of 163)• Macropapular rash which resolved after treatment discontinuation (median time to discontinuation:

~ 9 weeks)

• Cumulative discontinuation due to AEs by Week 12 – Both pegIFN/RBV/placebo 48 weeks and TVR/pegIFN 12 weeks: 10%– TVR/pegIFN/RBV 12 weeks: 12%– TVR/pegIFN/RBV 12 weeks pegIFN/RBV 12 weeks: 16%

• All treatment arms experienced comparable mean decreases in hemoglobin levels in the first 12 weeks– No incremental effect on neutrophil or platelet counts in TVR treatment arms

Dusheiko G, et al. EASL 2008. Abstract 58.

SPRINT-1: Boceprevir + PegIFN/RBV in Naive HCV G1

Kwo P, et al. EASL 2008. Abstract 995.

PegIFN/RBV* PegIFN/RBV*+ Boceprevir†

48-week treatment arm

PegIFN/RBV*+ Boceprevir†

48-week treatment arm

PegIFN/low-dose RBV arm + Boceprevir†

PegIFN/RBV*

Follow-up

Week 72Week 48Week 4 Week 28Baseline Week 40: interim

analysis

Lead in

No lead in

*PegIFN alfa-2b 1.5 µg/kg/wk and weight-based RBV 800-1400 mg/day.†Boceprevir 800 mg TID.

SPRINT-1: Undetectable HCV: Wks 4 / 12 of Boceprevir Therapy

Kwo P, et al. EASL 2008. Abstract 995.

0

20

40

60

80

100

Un

det

ecta

ble

* H

CV

RN

A (

%)

60

39

8

78 73

34

PegIFN/RBV lead-in pegIFN/RBV + boceprevir (n = 103)

PegIFN/RBV + boceprevir (n = 107)

PegIFN/RBV (n = 104)

*HCV RNA <15 IU/mL.

Duration 4 4 -- Boceprevir Rx 12 12 --

(weeks) 8 4 4 Total Rx 16 12 12

SPRINT-1: Highest WHO Grade Anemia 28 Weeks of Treatment

• Epoetin-alfa treatment– PegIFN/RBV lead-in arm pegIFN/RBV + boceprevir: 48%– PegIFN/RBV + boceprevir: 45% – PegIFN/RBV: 25%

Kwo P, et al. EASL 2008. Abstract 995.

Anemia Severity

0

20

40

60

80

100

Pat

ien

ts (

%)

Grade 0

23 21

45

Grade 1 Grade 2 Grade 3 Grade 4

50 5446

27 25

1010 0 0 0 0

PegIFN/RBV lead-in pegIFN/RBV + boceprevir (n = 206)

PegIFN/RBV + boceprevir (n = 226)PegIFN/RBV (n = 104)

STEALTH C-1: NTZ + PegIFN ± RBV in G4 HCV Patients

• Nitazoxanide (NTZ): broad-spectrum activity against parasites, anaerobic bacteria and viruses

Rossignol JF, et al. EASL 2008. Abstract 68.

180 µg/week pegIFN alfa-2a; weight-based RBV 1000-1200 mg/day; 500 mg BID NTZ.

NTZ NTZ + PegIFN

NTZ + PegIFN + RBV

PegIFN/RBV

Follow-up

Week 72Week 48Week 12Baseline

NTZ

NTZ NTZ + PegIFN

NTZ + PegIFN + RBVNTZ

n = 40

n = 28

n = 28

n = 12

n = 12

IFN-naive patients

IFN-experienced patients

STEALTH C-1: NTZ + PegIFN ± RBV in G4 HCV Patients

• 77 patients completed NTZ lead in – Week-12 HCV RNA

reduction: 0.26 log10 IU/mL (P = .0032)

• RVR (IFN-naive patients)– PegIFN + RBV: 38% – PegIFN + RBV + NTZ:

64% (P = .048)*

• No increase in AEs noted in NTZ arms vs SOC

Rossignol JF, et al. EASL 2008. Abstract 68.

0

20

40

60

80

100

SV

R (

%)

P = .023

10

30

50

70

90

50

61

79

PegIFN + RBVPegIFN + NTZPegIFN + RBV + NTZ

P = NS

IFN-Experienced Patients

8

25

N = 40 28 28 12 12 IFN-Naive Patients

* 16 wks total therapy (12 weeks NTZ + 4 weeks PegIFN + RBV + NTZ)

Target DrugTelaprevir (Vertex/JJ)Boceprevir (Schering)ITMN-191 (Intermune/Roche)TMC435350 (Tibotec/Medivir)

Balapiravir* (Roche)R7128 (Pharmassett/Roche)MK-0608 (Merck) BILB 1941(Boehringer-Ingelheim)GS 9190 (Gilead)A-837093 (Abbott)PF868554 (Pfizer)

DEBIO-025 (DebioPharm) NIM 811 (Novartis)

Stage (Phase)III

II/IIIII

IIIIaIIIIII

III

Protease

Polymerase

Cyclophilin B inhibitors

STAT-C: Specifically Targeted Antiviral Therapy for Hepatitis C

Slide Courtesy of Nelson D. Adapted from 2007 Roche HCV Symposium, AASLD 2007. Boston, MA.

*Generic name of R1626

Back Up

Data have not been reviewed or approved by FDA.

HCV-796 (Polymerase)

ISIS 14803(Antisense)

BILN 2061(Protease)

Heptazyme (Ribozyme)

NM-283 (Polymerase)

ACH-806/GS-9132 (NS4a)

ANA975(TLR agonist)

UT-231B(Imino sugar)

VX-497(IMPDH inhibitor)

JTK-003(Polymerase)

CPG 10101(TLR agonist)

R803(Polymerase)

Graveyard for HCV Compounds is Filling Up Quickly!

R7025(Interferon-alpha )

Back UpBack Up

Data have not been reviewed or approved by FDA.

Courtesy of Nelson D. Adapted from 2008 Roche HCV Symposium.

Communication and Education

Research and Treatment

State and Local Prevention Programs

Surveillance & Screening High Risk population

HCV

Hepatitis C Future

HCV Prevention and Detection

• Prevention

– Community Education

– Awareness

• Risk Factors • Complications

• Detection

– Testing high risk populations