Lawrence Serfaty

Service d’Hépatologie, UMR_S 938

Hôpital Saint-Antoine, Paris

Who, when and how to treat:

summary and take home messages

4th European Young Hepatologist Workshop, Bendor, 10-12th July

Approval of 1st generation PIs

Approval of new DAAs

Access to new HCV treatments

Market approval/early access program

for new DAAs in Europe in 2014

Sofosbuvir

Simeprevir

Daclatasvir

Sofosbuvir

Daclatasvir

Sofosbuvir

Simeprevir

Daclatasvir

EASL guidelines:

Treatment regimen in genotypes 1/2/3

G1a G1b G2 G3 Patient profile

Naïve Recommended Alternative option

SOF+ PR 12w SOF+DCV 12w ±R(cirrh) SOF+ SIM 12w ±R(cirrh) SIM 12w+PR 24w Q80K- SOF+R 24w

SOF+ PR 12w SOF+DCV 12w ±R(cirrh) SOF+ SIM 12w ±R(cirrh) SIM 12w+PR 24w DCV 12w +PR 24w SOF+R 24w

SOF + R 12w

SOF + PR 12w SOF + R 24w SOF+ DCV 12w

Relapsers Recommended Alternative option

SOF+ PR 12w SOF+DCV 24w ±R(cirrh) SOF+ SIM 12w ±R(cirrh) SIM 12S+PR 24w Q80K- SOF+R 24w

SOF+ PR 12w SOF+DCV 24w ±R(cirrh) SOF+ SIM 12w ±R(cirrh) SIM 12/24w+PR 24w DCV 12w+PR 24w SOF+R 24w

SOF + R 12w SOF + PR 12w SOF + R 24w SOF+ DCV 24w

Non responders Recommended Alternative option

SOF+ PR 12w or longer? SOF+DCV 24 w ±R SOF+ SIM 12 w ±R

SOF+ PR 12w or longer? SOF+DCV 24w ±R SOF+ SIM 12w ±R

SOF + R 16 -20w SOF + PR 12s SOF + R 24w SOF+ DCV 24w ±R(cirrh)

G1 PI failure SOF+DCV 24w SOF+DCV 24w

G4 G5 or 6

Patient profile

Naïve Recommended Alternative option

SOF+ PR 12w SOF+DCV 12 w ±R(cirrh) SOF+ SIM 12 w ±R(cirrh) SIM 12w+PR 24w DCV 12/24w+PR 24w SOF+R 24w

SOF+ PR 12w SOF+R 24w

Relapsers Recommended Alternative option

SOF+ PR 12w SOF+DCV 24w ±R(cirrh) SOF+ SIM 12 w ±R(cirrh) SIM 12w+PR 24w DCV 12/24w+PR 24w SOF+R 24w

SOF+ PR 12w SOF+R 24w

Non responders Recommended Alternative option

SOF+ PR 12w SOF+DCV 24 w ±R(cirrh) SOF+ SIM 12 w ±R(cirrh) SIM 12w+PR 24w DCV 12/24w+PR 24w SOF+R 24w

SOF+ PR 12w ? SOF+R 24w

EASL guidelines:

Treatment regimen in genotypes 4/5/6

Re-treatment of DAA-failure patients (EASL)

DAA failure regimen Retreatment

Sofosbuvir as only DAA Sofosbuvir + Simeprevir (G1 or G4)

Sofosbuvir + Daclatasvir

Boceprevir/telaprevir/simeprevir as

only DAA

Sofosbuvir + Daclatasvir

Daclatasvir as only DAA Sofosbuvir + Simeprevir (G1 or G4)

Sofosbuvir + simeprevir Sofosbuvir + Daclatasvir

Sofosbuvir + daclatasvir Sofosbuvir + Simeprevir (G1 or G4)

Who to treat (EASL)

• All treatment-naïve and -experienced patients with compensated

disease due to HCV should be considered for therapy

• Treatment should be prioritized for patients with significant fibrosis

(METAVIR score F3 to F4)

• Treatment is justified in patients with moderate fibrosis (METAVIR

score F2)

• In patients with no or mild disease (METAVIR score F0-F1), the

indication for and timing of therapy can be individualized

• Patients with decompensated cirrhosis who are on the transplant list

should be considered for IFN-free, ideally ribavirin-free therapy

High proportion of patients with no or mild

fibrosis included in phase 3 Pis trials

Jacobson IM, N Engl J Med 2011

Zeuzem S, N Engl J Med 2011

Treatment access

HCV screening rates in Europe

Belgium France Germany Italy Spain UK

HCV Screening, %

Observed, % (yr) 37

(2000)

57

(2004)

40

(2004)

40

(2005)

33

(2008–9)

30

(2004)

Estimated in 2011, % 50 64 48 46 35 34

HCV Genotype

G1, % 60 56 60 62 65 44

G2/3, % 27 32 37 34 23 53

Other

genotypes, %

13 12 3 4 12 3

Deuffic-Burban S, et al. Gastroenterology 2012

Proportion of patients ever treated with peginterferons per

100 prevalent HCV cases by country until end of 2005

Lettmeier B, et al J Hepatol 2008

16

12 12 11

1 < 1

Reduction in cumulative incidence of genotype 1

HCV-related deaths, 2012–2021 R

ed

ucti

on

in

cu

mu

lati

ve i

ncid

en

ce (

%)

25

20

10

5

0 Belgium France Germany Italy Spain UK

15

Greater reduction in HCV-related deaths with PI-based triple therapy than with dual therapy

-24%

-27%

-28%

-37%

-21%

-38%

Deuffic-Burban S, et al. Gastroenterology 2012

Dual therapy PI-based triple

therapy

Belgium France Germany Italy Spain UK

Red

ucti

on

in

cu

mu

lati

ve i

ncid

en

ce (

%)

Country

25

20

15

10

5

0

PI-based triple therapy with increased

screening and treatment access*

Dual therapy PI-based triple

therapy

Deuffic-Burban S, et al. Gastroenterology 2012

Reinforcing screening and treatment access: cumulative

incidence of genotype 1 HCV-related deaths, 2012–2021

*Assumes 75% of HCV-infected patients will be screened by 2015 and

one G1-infected patient in 2 will be treated in 2015 with PI-based triple therapy

-58%

-150%

-128%

-264%

-107%

-50%

Dramatic reduction in HCV-related deaths with PI-based triple therapy + reinforced screening and treatment access

2 889 385 veterans screened for HCV in 2011

Birth cohort screening: prevalence of HCV

infection by birth year in US veterans

Backus LI, et al; JAMA Intern Med 2013

Birth cohort vs current risk-based screening:

cost-effective in US

Compensated

cirrhosis

Decompensated

cirrhosis

HCC LT HCV-related

mortality

McGarry L, Hepatology 2012

Lifetime incremental reductions

Incremental cost effectiveness ratio (ICER) of $37,700

per quality-adjusted life year gained

Mena A, et al AASLD 2013, Abs. 2241

HCV seroprevalence by year of screening HCV seroprevalence by birth year

12

10

8

6

4

2

0 ≤ 1930 1931-

1940

1941-

1950

1951-

1960

1961-

1970

1971-

1980

1981-

1990

> 1990 0

2

4

6

10

8

12

2008 2012 2011 2010 2009

Pre

va

len

ce

(%

)

Year

Birth cohort screening in Europe? Prevalence of HCV by birth year in a Spanish hospital

92 143 HCV screening between 2008-2012

Rapid HCV diagnostic test

SAMPLE TYPE

Oral fluid

Venipuncture

Whole blood

Serum

Plasma

Fingerstick

Whole blood

MIX

TEST

INTERPRETATION

20 min

OraQuick® HCV Rapid Antibody Test Device

Accuracy of rapid HCV diagnostic tests Fingerstick whole blood

Specificity (CI95%)

Sensitivity (CI95%)

PPV NPV

OraQuick® HCV Rapid Ab Test

100% (97.9-100.0)

99.4% (97.7-99.9)

100% 98.4%

TOYO® anti-HCV test

98.2% (94.8-99.4)

96.2% (93.3-98.0)

99.0% 93.1%

Labmen® HCV test 100%

(94.4-100.0) 62.7%

(54.8-69.5) 100% 49.6%

Accuracy of OraQuick® Oral fluid

Specificity (CI95%)

Sensitivity (CI95%)

PPV NPV

OraQuick® HCV Rapid Ab Test

100% (97.9-100.0)

98.2% (95.9-99.1)

100% 96.6%

The present The future

HCV treatment challenge: simplicity

• Genotype

• Naïve or tt experienced

• Cirrhosis

• 8, 12 or 24 w

• RBV or no RBV

• BID or QD

• Drug-drug interaction

One pill a day for 4 weeks

100%

20%

10%

Screened

and treated

Cured

All HCV

patients

PEG-IFN/RBV

100%

20%

95% SVR

19%

100%

90%

85%

95% SVR

and improved screening

Courtesy M. Manns