ESSENCE OF SOFOSBUVIR 400mg.

Hepatitis
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Hepatitis
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Hepatitis
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Essence of Sofosbuvir
SOVIHEP 400 MG

HEPATITIS WEB STUDY HEPATITIS C ONLINE
Role of DAA's In HCV

Estimated 170 Million Persons With HCV
Infection Worldwide
•World Health Organization. Wkly Epid Rec .1999;74:425-427. World Health Organization. Hepatitis C:
Global Prevalence: Update. 2003. Farci P, et al. Semin Liver Dis. 2000;20:103-126. Wasley A, et al. Semin
Liver Dis. 2000;20:1-16.
•Europe
•8.9 million
•(1.03%)•Americas
•13.1 million
•(1.7%)
•Africa
•31.9 million
•(5.3%)
•Western
Pacific
•62.2 million
•(3.9%)
•Eastern
Mediterranean
•21.3 million
•(4.6%)
•Southeast Asia
•32.3 million
•(2.15%)

Hepatitis
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Hepatitis
web study2015
0
20
40
60
80
100
IFN 6m IFN 12m IFN/RBV 6m IFN/RBV 12 m Peg-IFN 12m Peg-IFN/RBV 12m Peg-IFN/RBV/DAA
SVR(%)
2001
1998
2011
Standard
Interferon
+ Ribavirin
Peginterferon
1991
+ DAAs
Milestones in Therapy of CHC:
Average SVR Rates from Clinical Trials
Adapted from US Food and Drug Administration,
Antiviral Drugs Advisory Committee Meeting, April 27-28, 2011, Silver Spring MD.
6%
16%
34%
42%
39%
55%
70+%

The Evolution of HCV Therapy
PegIFN/RBV
Protease inhibitor
Nucleos(t)ide polymerase inhibitor
Nonnucleoside polymerase inhibitor
NS5A inhibitor
Host targeting agent
2002 2012 Beyond

Current status of HCV…
• Treatment of HCV infection is evolving rapidly.
• The approval in 2013 of two new directacting antivirals—
sofosbuvir (a polymerase inhibitor) and simeprevir (a
second-generation protease inhibitor)—opens the door for
an all-oral regimen, potentially avoiding interferon and its
harsh side effects.
• Other direct-acting antivirals are under development.

GOAL OF TREATING HCV:
A SUSTAINED VIROLOGIC RESPONSE
• The aim of HCV treatment is to achieve a sustained
virologic response,
- defined as having no detectable viral RNA after completion
of antiviral therapy.
• SVR is associated with
1. better clinical outcomes,
2. lower morbidity and all-cause mortality,
3. improvement in liver histology

GOAL OF TREATING HCV:
A SUSTAINED VIROLOGIC RESPONSE
• This end point has
traditionally been assessed
at 6 months after the end
of therapy, but recent data
suggest the rates at 12
weeks are essentially
equivalent

HCV Life Cycle and DAA Targets
Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:991-1000.
Receptor binding
and endocytosis
Fusion
and
uncoating
Transport
and release
(+) RNA
Translation
and
polyprotein
processing
RNA replication
Virion
assembly
Membranous
web
ER lumen
LD
LD
ER lumen
LD
NS3/4
protease
inhibitors
NS5B polymerase
inhibitors
Nucleoside/nucleotide
Nonnucleoside

Each Drug Class Has Unique Features
NS3/4A
Protease
Inhibitors
NS5B Polymerase Inhibitors NS5A
Inhibitors
Cyclophilin A
InhibitorsNucleos(t)ide
Analogue
Non-
nucleos(t)ide
High efficacy
Low genetic
barrier to
resistance
Macrocyclic
or linear
Boceprevir
and
Telaprevir
already
licensed in
the US and
EU
Phase III:
BI 201335,
TMC435
Mimic natural
substrates of the
polymerase
Incorporated into
RNA chain
causing chain
termination
Broad genotypic
coverage
High genetic
barrier to
resistance
Phase III:
PSI-7977
Bind to several
different
allosteric
enzyme sites;
results in
conformational
change
Resistance
more frequent
than nucs
Several agents
in phase II
NS5A has role
in assembly of
replication
complex
Mechanism of
inhibition
under study
Phase III:
Daclatasvir
(BMS-790052)
Supports HCV-
specific RNA
replication,
protein
expression
Interacts with
NS2, NS5A,
NS5B
May regulate
polypeptide
processing,
viral assembly
Phase III:
Alisporivir

Source: http://1.bp.blogspot.com/-caP7g8bNY1E/UoEok96-TYI/AAAAAAAAK2s/J8w-sSYdXd8/s1600/newdda.PNG

On-Treatment Viral Kinetics
HCVRNA
0 12 24 36 484
HCV RNA negative in blood
Weeks
First phase
Second phase
Ribavirin
PEG-Interferon

First phase
0 12 24 36 484
Weeks
Improve both first and second phase kinetics
HCVRNA
Boceprevir /
Telaprevir
1. Increase efficacy

Second
phase
First phase
HCVRNA
0 12 24 36 484
Weeks
Improve both first and second phase kinetics
1. Increase efficacy
2. Shorten treatment duration
Boceprevir /
Telaprevir

Nucleoside/tide Analog Polymerase
Inhibitors Are Chain-Terminators
AG C
UC GA CGGG
C
RNA chain
cannot be
elongated
NI Chain-terminator
3’
5’
5’
Template strand
Primer strand
NI

Sofosbuvir
• Approval Status: FDA approved December 6, 2013
• Indication for HCV Monoinfection and HCV-HIV Coinfection
- GT 1,4: Sofosbuvir + peginterferon + ribavirin (12 weeks)
- GT 2: Sofosbuvir + ribavirin (12 weeks)
- GT 3: Sofosbuvir + ribavirin (24 weeks)
• Additional Indication for HCV Monoinfection
- GT 1 (interferon ineligible): Sofosbuvir + ribavirin (24 weeks)
- HCC and awaiting transplant: Sofosbuvir + ribavirin (up to 48 weeks)
• Class & Mechanism
- Nucleotide analog inhibitor of NS5B polymerase enzyme
• Dosing: 400 mg PO once daily with or without food
• Adverse Effects (AE) attributable to Sofosbuvir
- Fatigue, headache

Sofosbuvir
• Dosing in Renal Impairment
- No dose adjustment is required for patients with mild or moderate
renal impairment.
- No dose recommendation can be given for patients with severe renal
impairment (eGFR <30 mL/min/1.73m2)or with end stage renal disease due
to higher exposures (up to 20 -fold) of the predominant sofosbuvir metabolite

Hepatitis
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Hepatitis
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Hepatitis
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Sofosbuvir: Details of Key Phase 2/3 Studies

Treatment Naïve
Phase 2 Study – Genotype 1, 4 & 6

Source: Kowdley K, et al. Lancet. 2013;381:2100-7.
Sofosbuvir + Peginterferon + Ribavirin in Genotypes 1,4,6
ATOMIC Trial: Design
N =14
Drug Dosing
Sofosbuvir (SOF): 400 mg once daily
Ribavirin (RBV) weight-based and divided bid: 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg
Peginterferon alfa-2a (PEG): 180 µg once weekly
Cohort A
n = 52
GT 1
GT4
GT6
SOF + PEG + RBV
SOF + PEG + RBV
SOF + PEG + RBV SVR24
SVR24
SVR24
Cohort B
n = 125
Cohort C
n = 155
SOF
SOF + RBV
0 12 48Week 24 36

ATOMIC Trial: Results, by Cohort (Regimen)
ATOMIC: SVR 24 by Cohort (Regimen)
89 89 87
0
20
40
60
80
100
Cohort A Cohort B Cohort C
Patients(%)withSVR24
46/52 97/109 135/155
Patients with Genotype 1, 4, or 6
The rates of sustained virologic response were very high
and were not significantly different among the three groups:
89%, 89%, and 87%, respectively

ATOMIC Trial: Results, by Cohort (Regimen)
ATOMIC: SVR 24 by Genotype
88
82
100
0
20
40
60
80
100
GT 1 GT 4 GT 6
264/300 9/11 5/5
Notes: (1) No patients with Genotype 5 enrolled in study
(2) All patients with Genotype 4 or 6 received 24 weeks of SOF + PEG + RBV
(3) The 2 patients with Genotype 4 and failure resulted from lost to follow-up at end of treatment

ATOMIC Trial: Implications
1. There is no benefit in prolonging treatment with sofosbuvir beyond 12 weeks,
since adverse events increased without any improvement in the rate of
sustained virologic response
2. There is a very low likelihood of developing viral resistance or mutation when
using sofosbuvir.
3. There is no role for response-guided therapy, a concept used with protease
inhibitor-based regimens in which patients who have complete clearance of
the virus within the first 4 weeks of treatment (a rapid virologic response) and
remain clear through 12 weeks of treatment (an extended rapid viral
response) can be treated for a shorter duration without decreasing the
likelihood of a sustained virologic response
• .

Treatment Naïve
Phase 3 Study - Genotype 1, 4, 5 & 6

Source: Lawitz E, et al. N Engl J Med. 2013;368:1878-87.
Sofosbuvir + PEG + RBV: Treatment-Naive HCV GT 1,4,5,6
NEUTRINO Trial: Design
Sofosbuvir + PEG + RBVN=327
Drug Dosing
Sofosbuvir: 400 mg once daily
Peginterferon alfa-2a: 180 µg once weekly
Ribavirin (weight-based and in 2 divided doses): 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg
0 12 24Week
SVR12

NEUTRINO Trial: Results
NEUTRINO: HCV RNA <25 IU/ml by Study Timepoint
99 99
90
0
20
40
60
80
100
Week 4 Week 12 (End of Tx) SVR12
Patients(%)withHCVRNA<25IU/ml
SVR = sustained virologic response
321/325 326/327 295/327

NEUTRINO Trial: Results
NEUTRINO: SVR 12 by Liver Disease
92
80
0
20
40
60
80
100
No Cirrhosis Cirrhosis
PatientswithSVR12(%)
252/273 43/54

NEUTRINO Trial: Conclusions
Conclusions: “In the open-label, single-group study, 12
weeks of treatment with sofosbuvir plus peginterferon-
ribavirin had high efficacy in previously untreated patients
with genotype 1 or 4 infection, with apparent reductions in
adverse effects.”
*Note: This conclusion pertains to both the NEUTRINO and FISSION trials, which were published in tandem

Treatment Naïve
Phase 2 Study – Genotype 1, 2 & 3 (Sof + Peg + RBV)

Source: Lawitz E, et al. Lancet Infect Dis. 2013;13:401-8.
Sofosbuvir + Peginterferon + Ribavirin in Genotypes 1-3
PROTON Trial: Design
N =14Drug Dosing
Sofosbuvir (SOF): 400 mg once daily, except as designated in arm that received 200 mg once daily
Peginterferferon alfa-2a (PEG): 180 µg once weekly
n = 48
SOF + PEG + RBVn = 25GT 2, 3
GT 1
SOF (200 mg) +
PEG + RBV
+ RVR
PEG + RBV
- RVR PEG + RBV
n = 47 SOF (400 mg) +
PEG + RBV
+ RVR
PEG + RBV
- RVR PEG + RBV
SOF + PEG + RBVn = 26
0 24 4812 72Week

Sofosbuvir + Ribavirin + Peginterferon in Genotypes 1-3
PROTON Trial: Results, by Genotype
PROTON: SVR 24
90 91
58
92
0
20
40
60
80
100
SOF 200 mg + PR SOF 400 mg + PR PR SOF 400 mg + PR
41/48 42/47 15/26 23/25
Genotype 1 Genotype 2 or 3

Sofosbuvir + Ribavirin + Peginterferon in Genotypes 1-3
PROTON Trial: Conclusions
Interpretation: “Our findings lend support to the further assessment, in
phase 2 and 3 trials, of sofosbuvir 400 mg plus peginterferon and
ribavirin for 12 weeks in treatment-naive patients with HCV genotype-1.”

Treatment Naïve & Experienced
Phase 2 Study – Genotype 1, 2 & 3 (Sof + Peg + RBV)

Source: Gane EJ, et al. N Engl J Med. 2013;368:34-44.
Sofosbuvir and Ribavirin +/- Peginterferon in GT 1-3
ELECTRON Trial (Arms 1-8): Design
SOF + RBV
N =14
Drug Dosing
Sofosbuvir (SOF): 400 mg once daily
Peginterferon alfa-2a (PEG): 180 µg once weekly
n = 9
n = 10
SOF + RBV + PEG (week 1-4)
n = 10 SOF + RBV + PEG (week 1-8)
n = 11 SOF + RBV + PEG
SOF
SOF + RBV + PEG
SOF + RBV
SOF + RBV SVR12
n = 10
n = 10
n = 10
n = 25
SVR12
SVR12
SVR12
SVR12
SVR12
SVR12
SVR12GT 1 Null
GT 2,3
Naïve
GT 1 Naive
0 20 24Week 8 12

Sofosbuvir and Ribavirin +/- Peginterferon in GT 1-3
ELECTRON Trial (Arms 1-8): Results
ELECTRON: SVR 12, by Treatment Regimen
100 100 100 100
60
100
10
84
0
20
40
60
80
100
SOF 12 wks
RBV 12 wks
SOF 12 wks
RBV 12 wks
PEG wk 1-4
SOF 12 wks
RBV 12 wks
PEG wk 1-8
SOF 12 wks
RBV 12 wks
PEG 12 wks
SOF 12 wks SOF 8 wks
RBV 8 wks
PEG 8 wks
SOF 12 wks
RBV 12 wks
SOF 12 wks
RBV 12 wks
PatientswithSVR(%)
10/10
Genotype 2 or 3 (all treatment naïve)
Genotype 1
Exp-Null Naive
9/9 10/10 11/11 6/10 10/10 21/25
1/10

Sofosbuvir + RBV in Treatment-Experienced HCV GT 2 or 3
ELECTRON Trial (Arms 1-8): Conclusions
Conclusions: “Sofosbuvir plus ribavirin for 12 weeks may
be effective in previously untreated patients with HCV
genotype 1, 2, or 3 infection.”

Treatment Naïve
Phase 3 Study - Genotype 2 & 3 ((Sof + RBV) & (Peg + RBV))

N=243
N=256 SVR12
SVR12
Sofosbuvir + Ribavirin for Treatment-Naïve HCV GT 2 or 3
FISSION Trial: Design
Peginterferon + RBV (fixed-dose)
Sofosbuvir +
RBV (weight-based)
Drug Dosing
Peginterferon alfa-2a: 180 µg once weekly
Weight-based Ribavirin (in 2 divided doses): 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg
Fixed-dose Ribavirin (in 2 divided doses): 800 mg/day
Week 0 12 3624

FISSION Trial: Results
FISSION: SVR12 by Genotype
67
97
56
67
78
63
0
20
40
60
80
100
GT 2 and 3
(n=496)
GT 2
(n=137)
GT 3
(n=359)
Sofosbuvir + RBV PEG + RBV
RBV = Ribavirin; PEG = Peginterferon
68/70 52/67 102/183 110/176170/253 162/243

FISSION Trial: Results
FISSION: SVR12 by Presence of Cirrhosis
72
47
74
38
0
20
40
60
80
100
No Cirrhosis
(n=397)
Cirrhosis
(n=99)
Sofosbuvir + RBV PEG + RBV
RBV = Ribavirin; PEG = Peginterferon
147/204 23/49 19/50143/193

FISSION Trial: Conclusions
Conclusions: “In the randomized trial of previously untreated patients
with genotype 2 or 3 infection, the efficacy of the all-oral regimen of
sofosbuvir plus ribavirin was similar to that of peginterferon–ribavirin, but
response rates among patients with genotype 3 infection were lower than
the rates among those with genotype 2 infection.”
*Note: This conclusion pertains to both the FISSION and NEUTRINO trials, which were published in tandem

Treatment Naïve & Experienced
Phase 3 Study - Genotype 2 & 3 (Sof + RBV)

Source: Zeuzem S, et al. N Engl J Med. 2014;370:1993-2001.
Sofosbuvir and Ribavirin for HCV GT 2 or 3
VALENCE Trial: Study Features
VALENCE Trial: Features
 Design: Randomized, phase 3, using sofosbuvir + ribavirin in treatment
naive or experienced, chronic HCV GT 2 or 3
 Setting: Europe
 Entry Criteria
- Chronic HCV Genotype 2 or 3
- Treatment naïve or treatment experienced
- Platelet ≥ 50,000
 Patient Characteristics (range in different treatment arms)
- N = 419
- Sex: male (55-62%)
- Race: white (89-100%)
- Cirrhosis: (14-23%)
- IL28B Genotype: non-CC (64-74%)
 End-Points: Primary = SVR12; Secondary = safety

VALENCE: Treatment Arms
Sofosbuvir + RBV
(n = 73)
Sofosbuvir + RBV
(n = 250)
GT 2
GT 3
Drug Dosing
Sofosbuvir 400 mg once daily
Ribavirin (weight-based and divided bid): 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg
Original Study Protocol: Placebo versus 12 weeks treatment for GT 2 and 3.
Amended Protocol: GT3 treatment extended from 12 to 24 weeks; Placebo arm offered alternative treatment
Note: 85 patients enrolled in placebo arm
0 24 36Week 12
SVR12
SVR12

VALENCE: Results for Treatment Naïve and Experienced
VALENCE: SVR12 by Genotype
93
85
0
20
40
60
80
100
Genotype 2 Genotype 3
Patient(%)withSVR12
12-week Treatment 24-week Treatment
68/73 213/250

VALENCE: Results
VALENCE: SVR12 by Genotype and Prior Treatment Experience
93
85
97 94
90
79
0
20
40
60
80
100
Genotype 2 Genotype 3
All Treatment-Naïve Treatment-Experienced
68/73 213/25031/32 37/41 99/105 114/145

Treatment Naïve
Phase 2 Study - Genotype 1 (Peg not an option)

Source: Osinusi A, et al. JAMA. 2013;310:804-11.
Sofosbuvir and Ribavirin for Treatment-Naïve HCV GT 1
NIH SPARE Trial: Features
NIAID/NIH Trial: Features
 Design
- Randomized, open-label, 2-part, phase 2 study of sofosbuvir and ribavirin
- Part 1: “proof of concept”
- Part 2: low dose versus weight-based dose of ribavirin in GT-1
 Setting: Single center: NIAID
 Entry Criteria: HCV genotype 1; treatment-naïve
 Patient Characteristics
- N = 60 HCV-monoinfected patients
- HCV Genotype: 1A (70%), 1B (30%)
- IL28B Genotype: 81% non-CC
- Age and Sex: median 54 (range 48-57); 62% male
- Race: 83% black; 13% white
- Liver disease: 23% had advanced fibrosis (F3-F4 by Knodell-HAI scoring)
 Primary end-points: Efficacy (SVR24) and safety

Part 2
N =50
Sofosbuvir + RBV (low-dose)
24 weeks
Sofosbuvir + RBV (wt-based)
24 weeks
Part 1
N =10
NIH SPARE Trial: Design
SVR24
Sofosbuvir + RBV (wt-based)
24 weeks
SVR24
N =25
N =25
Drug Dosing
Low-dose Ribavirin (divided bid): 800 mg/day
Weight-based Ribavirin (divided bid): 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg
SVR24
0 24 48Week

NIH SPARE Trial: Part 1 Results
NIH SPARE Part 1: HCV <12 IU/ml by Study Timepoint
80
90 90
0
20
40
60
80
100
All 10 patients in Part 1 received sofosbuvir plus weight-based ribavirin
8/10 9/10 9/10

NIAID/NIH Part 2: HCV RNA <12 IU/ml by Study Timepoint
96
88
48
96 96
68
0
20
40
60
80
100
SOF + RBV (low dose) SOF + RBV (weight based)
SOF = Sofosbuvir; RBV = Ribavirin
24/25 24/25 22/25 24/25 12/25 17/25

NIH SPARE Part 2: SVR24 by Fibrosis Stage
56
29
74
50
0
20
40
60
80
100
Early Stage (0-1*) Advanced (3-4*)
Fibrosis Stage
(Knodell Histology Activity Index Scoring System)
SOF +RBV (Low Dose) SOF +RBV (Wt-Based)
SOF = Sofosbuvir; RBV = Ribavirin
3/62/714/1910/18

21
82
63
78
0
20
40
60
80
100
>800,000 IU/ml <800,000 IU/ml
HCV RNA Level
SOF +RBV (Low Dose) SOF +RBV (Wt-Based)
NIH SPARE Part 2: SVR24 by Baseline HCV RNA Level
SOF= Sofosbuvir; RBV = Ribavirin
7/99/1110/163/14

NIH SPARE Trial: Conclusions
Conclusion: “In conclusion, treatment with a 24-week regimen of
sofosbuvir and ribavirin resulted in an SVR rate of 68% in the weight-
based ribavirin regimen and 48% in the low-dose ribavirin regimen
among patients with chronic HCV and unfavorable traditional predictors
of treatment response who are representative of the demographics of the
US HCV epidemic.”

Characteristics of New Generation DAA Regimens
• Antiviral activity seen in all genotypes
• High Barrier to Resistance
• Higher SVR rates and shorter treatment duration
• Oral, IFN-free, combination regimens have less side effects
and higher SVR rates
• Patients with cirrhosis and decompensated cirrhosis will
benefit from less toxic regimens

Sofosbuvir
Drug-Drug Interactions
Sofosbuvir not recommended for coadministration with*:
• Anticonvulsants
- Carbamazepine
- Oxcarbazepine
- Phenobarbital
- Phenytoin
• Antimycobacterials
- Rifabutin
- Rifampin
- Rifapentine
• Herbal Supplements
- St. John’s wort
• HIV Protease Inhibitors
- Tipranavir/ritonavir
Source: Sofosbuvir (Sovaldi) Prescribing Information. Gilead Sciences.
*Not recommended because of potential marked decrease in sofosbuvir levels

EASL HCV Guidelines 2014: Genotype 1
Genotype Options for Therapy
Genotype 1*
PegIFN/ribavirin + sofosbuvir: 12 wks (A1)
PegIFN/ribavirin + simeprevir†: 12 wks, followed by 12 wks of pegIFN/ribavirin in
previously untreated pts and prior relapsers (A1), or 36 wks of pegIFN/ribavirin in
previous partial responders and null responders (B1)
PegIFN/ribavirin + daclatasvir (genotype 1b only; B1): 12 wks followed by 12 wks of
pegIFN/ribavirin alone or a further 12 wks of pegIFN/ribavirin + daclatasvir
(response-guided therapy) (B2)
Sofosbuvir + ribavirin: 24 wks for interferon-intolerant pts only, where no other
interferon-free option available (B2)
Sofosbuvir + simeprevir: 12 wks (ribavirin may be added for previous nonresponders
& cirrhotics) (B1)
Sofosbuvir + daclatasvir: 12 wks in previously untreated pts; 24 wks in treatment-
experienced patients (including TVR/BOC-experienced patients) (ribavirin may be
added in previous nonresponders and cirrhotics) (B1)
EASL. J Hepatology. 2014;60:392-420.
*In settings where recommended options are not available, treatment with pegIFN/ribavirin + TVR or BOC
remains acceptable.
†Not recommended in pts with genotype 1a and detectable Q80K polymorphism.

EASL HCV Guidelines 2014: Genotype 2-6
Genotype Options for Therapy
Genotype 2*
Sofosbuvir + ribavirin: 12 wks (16-20 weeks in cirrhotic patients, especially treatment experienced) (A1)
PegIFN/ribavirin + sofosbuvir: 12 wks for cirrhotic and/or treatment-experienced patients (B1)
Genotype 3*
Sofosbuvir + ribavirin: 24 wks (unsuitable for treatment-experienced cirrhotics, no specific alternative
proposed) (A2)
PegIFN/ribavirin + sofosbuvir: 12 wks (A2)
Sofosbuvir + daclatasvir: 12 wks (24 wks for treatment-experienced patients) (B1)
Genotype 4*
PegIFN/ribavirin + sofosbuvir 12 weeks (B1)
PegIFN/ribavirin + simeprevir: 12 wks, followed by 12 wks of pegIFN/ribavirin in previously untreated
patients & prior relapsers (B1), or 36 wks of pegIFN/ribavirin in previous partial responders & null
responders (B1)
PegIFN/ribavirin + daclatasvir: 12 wks followed by 12 wks of pegIFN/ribavirin alone or a further 12 wks of
pegIFN/ribavirin + daclatasvir (response-guided therapy) (B1)
Sofosbuvir + ribavirin: 24 wks for interferon-intolerant patients (C2)
Sofosbuvir + simeprevir: 12 wks (ribavirin may be added in previous nonresponders and cirrhotics) (B2)
Sofosbuvir + daclatasvir: 12 wks in previously untreated patients; 24 wks in treatment-experienced
patients (ribavirin may be added in previous nonresponders and cirrhotics) (B2)
Genotype
5/6*
PegIFN/ribavirin + sofosbuvir 12 wks (B1)
Sofosbuvir + ribavirin: 24 wks for interferon-intolerant patients (C2)
EASL. J Hepatology. 2014;60:392-420.
*In settings where recommended options are not available, treatment with pegIFN/ribavirin remains acceptable.

AASLD HCV Guidelines 2014
Genotype 1

Genotype 2

Genotype 3

Genotype 4

Summary of collated trials data
The emergence of all-oral regimens for HCV treatment with increasingly
sophisticated agents such as sofosbuvir will dramatically alter the management of
HCV patients.

Preliminary Results of New
Interferon Free Regimens in Phase 2
Trials
Regimen SVR
Rate
Duration
in Weeks
Sufosbuvir + Ledipasvir + RBV >95% 8-12
ABT450/r + ABT267 + ABT333 + RBV 12 ~90%
Faldaprevir + 207127 + RBV (GT1B) 90% 12-24
DCV + ASV +BMS-791325 88-
94%
12-24
Presentations at European Association of Study of Liver Disease
and Press releases

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ESSENCE OF SOFOSBUVIR 400mg.

Notes de l'éditeur