1392GR1700862-01 3/2017

1392GR1700862-01 3/2017

1392GR1700862-01 3/2017

UPDATE ON THE KEY

TREATMENT

GUIDELINES OVER

THE PAST YEAR

Nikolaos K. Gatselis

Department of Medicine

& Research Laboratory of Internal Medicine,

Larissa Medical School,

Thessaly University

1392GR1700862-01 3/2017

Disclosure

• Research Support: Gilead, Janssen, Bayern, Roche,

Abbvie, Regulus, MSD

• Speaker Bureau: BMS, ABBVIE

• Travel expenses: Janssen, BMS, Novartis, Gilead, TEVA,

Abbvie

5

Who should be treated?

All patients with chronic HCV infection are

candidates for antiviral treatment and

potentially be treated with the optimum

regimen which offers higher efficacy and better

safety and tolerability.

HASL 2017

Prioritization for administration

of DAAs • moderate fibrosis or cirrhosis (Ishak: 2-6, METAVIR F2-F4, Fibroscan >7.5

kPa)

• HCV recurrence after liver transplantation

• HIV co-infection or HBV-co-infection

• severe extrahepatic manifestations (cryoglobulinemia, B-cell NHL)

• chronic hemoglobinopathies with hepatic or non-hepatic complications due to chronic hemolysis

• hemophiliacs and patients with other hemostasis disorders

• chronic renal failure (regardless of hemodialysis)

• patients at risk of a rapid evolution of liver disease (immunosuppression or concurrent disease)

• contraindication for IFNα or ribavirin (regardless of liver fibrosis stage)

• high risk groups for HCV transmission or exposure (active injection drug users, multiple sexual partners)

HASL 2017

Greek authorities (11/2016)

• F3 – only treatment experienced

• F4 – naïve or treatment experienced

• Liver transplant recipients with HCV

recurrence

• Severe extra-hepatic manifestations (?)

DAAs Approved in 2014

DAAs Approved in 2015

DAAs Approved in 2016

HASL2017

Genotype 1a non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+DCV 12w 12w 12w12w +RBV

24w

SOF/LDV 8w 12w 12w12w +RBV

24w

PRV/r/OBV+DSV 12w +RBV 12w +RBV 12w +RBV12w +RBV

24w +RBV (null-R)

SOF/VEL 12w 12w 12w 12w

EBR/GZR

12w (RAV- or HCVRNA ≤

800,000 IU/ml)16w +RBV (RAV+

or HCV RNA > 800,000 IU/ml

12w (RAV- or HCVRNA ≤

800,000 IU/ml)16w +RBV (RAV+

or HCV RNA > 800,000 IU/ml

12w (RAV- or HCVRNA ≤

800,000 IU/ml)16w +RBV (RAV+

or HCV RNA > 800,000 IU/ml

12w (RAV- or HCVRNA ≤

800,000 IU/ml)16w +RBV (RAV+

or HCV RNA > 800,000 IU/ml

EASL 2016

Genotype 1a non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+DCV 12w12w +RBV

24w12w

12w +RBV24w

SOF/LDV 8-12w12w +RBV

24w12w

12w +RBV24w

PRV/r/OBV+DSV 12w +RBV 12w +RBV 24w +RBV 24w +RBV

SOF/VEL 12w 12w 12w 12w

EBR/GZR

12w (RAV- or HCVRNA ≤

800,000 IU/ml)16w +RBV (RAV+

or HCV RNA > 800,000 IU/ml

12w (RAV- or HCVRNA ≤

800,000 IU/ml)16w +RBV (RAV+

or HCV RNA > 800,000 IU/ml

12w (RAV- or HCVRNA ≤

800,000 IU/ml)16w +RBV (RAV+

or HCV RNA > 800,000 IU/ml

12w (RAV- or HCVRNA ≤

800,000 IU/ml)16w +RBV (RAV+

or HCV RNA > 800,000 IU/ml

AASLD2016

Genotype 1a non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+DCV 12w 12w 24w ±RBV 24w ±RBV

SOF/LDV 12w 12w 12w12w +RBV

24w

PRV/r/OBV+DSV 12w +RBV 12w +RBV 24w +RBV 24w +RBV

SOF/VEL 12w 12w 12w 12w

EBR/GZR12w (RAV-)

16w +RBV (RAV+)12w (RAV-)

16w +RBV (RAV+)12w (RAV-)

16w +RBV (RAV+)12w (RAV-)

16w +RBV (RAV+)

HASL2017

Genotype 1b non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+DCV 12w 12w 12w12w +RBV

24w

SOF/LDV 8w 12w 12w12w +RBV

24w

PRV/r/OBV+DSV 8w (?F3) 12w 12w 12w

SOF/VEL 12w 12w 12w 12w

EBR/GZR 12w 12w 12w 12w

EASL2016

Genotype 1b non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+DCV 12w 12w 12w 12w

SOF/LDV 8-12w 12w 12w 12w

PRV/r/OBV+DSV 8-12w 12w 12w 12w

SOF/VEL 12w 12w 12w 12w

EBR/GZR 12w 12w 12w 12w

AASLD2016

Genotype 1b non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+DCV 12w 12w 24w ±RBV 24w ±RBV

SOF/LDV 12w 12w 12w12w +RBV

24w

PRV/r/OBV+DSV 12w 12w 12w 12w

SOF/VEL 12w 12w 12w 12w

EBR/GZR 12w 12w 12w 12w

Genotype 1: SOF/VELASTRAL-1 Phase III, TN and TE (32%), Gt 1, 2, 4, 5, 6, 19% cirrhosis, 12wks

Feld, NEJM 2015

Genotype 1: GZR/EBRPooled efficacy population, G1a, Phase II and III trials, 12w, no RBV

Genotype 1: SOF/LDV

8w in naïve, non-Cirrhotics

Genotype 1b: PRV/r/OBV+DSV

8w in naïve w/o cirrhosis

GARNET study

Genotype 1bTreatment naïve

No cirrhosis F0-F3

SVR 13/15 (87%) F3 patients

Welzel, EASL Conference 2016

TURQUOISE-IISVR12 rate of 92-96% in 380 HCV GT-1 with Compensated

Cirrhosis treated with OBV/PTV/r + DSV + RBV

n=380, GT1a, GT1b, Cirrhosis (CP-A), TN, TE

Poordad, NEJM 2014

HASL2017

Genotype 2 non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+RBV 12w - - -

SOF+DCV* 12w 12w 12w 12w

SOF/VEL 12w 12w 12w 12w

*limited data

Genotype 2: SOF/VELASTRAL 2 – Phase III, TN and TE (14%), Gt2, 14% cirrhosis, 12 w

Foster, NEJM 2015

EASL2016

Genotype 2 non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+RBV - - -

SOF+DCV 12w 12w 12w 12w

SOF/VEL 12w 12w 12w 12w

AASLD2016

Genotype 2 non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+RBV - - -

SOF+DCV 12w 12w 16-24w 16-24w

SOF/VEL 12w 12w 12w 12w

HASL2017

Genotype 3 non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+DCV 12w 12w +RBV 12-24w +RBV 12-24w +RBV

SOF/VEL 12w 12w +RBV24w

12w +RBV24w

12w +RBV24w

EASL2016

Genotype 3 non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+DCV 12w12w +RBV (RAV+)

24w (RAV+)24w +RBV 24w +RBV

SOF/VEL 12w 12w +RBV24w (RAV+)

12w +RBV24w

12w +RBV24w

AASLD2016

Genotype 3 non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+DCV 12w 12w 24w ±RBV 24w +RBV

SOF/VEL 12w12w 12w 12w +RBV

Genotype 3: SOF + DCVALLY-3 – Phase III, TN and TE, Gt3, F0-F4, 12 w

Nelson, Hepatology 2015

Genotype 3: SOF + DCV +RBV• ALLY-3+: SVR12 by Cirrhosis Status

Leroy, Hepatology 2016

ALLY-3+, Phase III, TN and TE, Gt3, F3F4, 12-16 w

Genotype 3: SOF/VELASTRAL 3 – Phase III, TN and TE, Gt3, F0-F4, 12 w

Foster, NEJM 2015

HASL2017

Genotype 4 non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+DCV 12w12w +RBV

24w12w

12w +RBV24w

SOF/LDV 12w12w +RBV

24w12w

12w +RBV24w

PRV/r/OBV 12w +RBV 12w +RBV 12w +RBV 12w +RBV

SOF/VEL 12w 12w 12w 12w

EBR/GZR 12w

12w (HCV RNA≤800,000

IU/ml)16w +RBV (HCV RNA>800,000

IU/ml)

12w

12w (HCV RNA≤800,000

IU/ml)16w +RBV (HCV RNA>800,000

IU/ml)

*limited data

*limited data

*limited data

ΕASL2016

Genotype 4 non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+DCV 12w12w +RBV

24w12w

12w +RBV24w

SOF/LDV 12w12w +RBV

24w12w

12w +RBV24w

PRV/r/OBV 12w +RBV 12w +RBV 12w +RBV 12w +RBV

SOF/VEL 12w 12w 12w 12w

EBR/GZR 12w

12w (HCV RNA≤800,000

IU/ml)16w +RBV (HCV RNA>800,000

IU/ml)

12w

12w (HCV RNA≤800,000

IU/ml)16w +RBV (HCV RNA>800,000

IU/ml)

AASLD2016

Genotype 4 non-Cirrhotics Cirrhotics

naive exp naive exp

SOF+DCV

SOF/LDV 12w 12w 12w12w +RBV

24w

PRV/r/OBV 12w +RBV 12w +RBV 12w +RBV 12w +RBV

SOF/VEL 12w 12w 12w 12w

EBR/GZR 12w

12w (relapsers)16w +RBV (on-

treatment failures)

12w

12w (relapsers)16w +RBV (on-

treatment failures)

Genotype 4: SOF/VELASTRAL 1 – Phase III, TN and TE (32%), Gt4, 19% cirrhosis, 12 w

Feld, NEJM 2015

100%

0

25

50

75

100

GT4N=116

SVR

12

rat

e (

%)

Genotype 4: OBV/PTV/r +RBV

Asselah, Lancet Gastroenterol Hepatol 2016Waked, Lancet Gastroenterol Hepatol 2016

Genotype 4: GRZ/EBRIntegrated analysis of Phase II and III trials, Gt4, w/o cirrhosis

Asselah, AASLD 2015

HASL2017

Genotype 5,6

non-Cirrhotics Cirrhotics

naive exp naive exp

SOF/LDV 12w 12w +RBV 12w 12w +RBV

SOF/VEL 12w 12w 12w 12w

Monitoring Patients

Prior

• FBC, INR, LFTs, eGFR• HCV genotype• HCV RNA• Fibrosis stage• DDIs• Pregnancy• *RAVs testing

During• FBC every 2-4weeks (RBV)• ALT every 4 weeks• HCV RNA (EOT in non-adherence or DAAs failure)

Post• HCV RNA (SVR12) (48w)• US every 6 months in F4

Conclusions

• HCV is the only curable chronic viral infection

• Extension of priorities for access to DAAs

• Predominance of IFN-free regimens

• Simplification of treatment regimens

– shorter duration (<12 weeks)

– without ribavirin

• Testing for HCV RAVs should not be a barrier to treatment

• Treatment individualization

Thank you for your attention!