essence of sofosbuvir 400mg

Hepatitisweb study

Hepatitisweb study

Hepatitisweb study

Essence of SofosbuvirSOVIHEP 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%)

Hepatitisweb study

Hepatitisweb 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

SV

R (

%)

20011998

2011

StandardInterferon

+ 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/RBVProtease inhibitorNucleos(t)ide polymerase inhibitorNonnucleoside polymerase inhibitorNS5A inhibitorHost 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

http://2.bp.blogspot.com/-pmuVnAkVU3Q/UxdwCAARZJI/AAAAAAAALsM/F7qdAKDCVjM/s1600/T1_medium.gif

http://2.bp.blogspot.com/-pmuVnAkVU3Q/UxdwCAARZJI/AAAAAAAALsM/F7qdAKDCVjM/s1600/T1_medium.gif

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

Therapeutic Gain With DAAs

On-Treatment Viral Kinetics

HC

V R

NA

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

HC

V R

NA Boceprevir /

Telaprevir

1. Increase efficacy

Second

phase

First phase

HC

V R

NA

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

Hepatitisweb study

Hepatitisweb study

Hepatitisweb study

Sofosbuvir: Details of Key Phase 2/3 Studies


Treatment NaïvePhase 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 DosingSofosbuvir (SOF): 400 mg once dailyRibavirin (RBV) weight-based and divided bid: 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kgPeginterferon alfa-2a (PEG): 180 µg once weekly

Cohort An = 52

GT 1

GT4

GT6

SOF + PEG + RBV

SOF + PEG + RBV

SOF + PEG + RBV SVR24

SVR24

SVR24

Cohort Bn = 125

Cohort Cn = 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

Pati

en

ts (

%)

wit

h S

VR

24

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


8882

100

0

20

40

60

80

100

GT 1 GT 4 GT 6

Pati

en

ts (

%)

wit

h S

VR

24

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 NaïvePhase 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

Pa

tie

nts

(%

) w

ith

HC

V R

NA

< 2

5 I

U/m

l

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

Pati

en

ts w

ith

SV

R12 (

%)

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 NaïvePhase 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 DosingSofosbuvir (SOF): 400 mg once daily, except as designated in arm that received 200 mg once dailyRibavirin (RBV) weight-based and divided bid: 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kgPeginterferferon alfa-2a (PEG): 180 µg once weekly

n = 48

SOF + PEG + RBVn = 25GT 2, 3

GT 1

SOF (200 mg) +

PEG + RBV

+ RVRPEG + RBV

- RVR PEG + RBV

n = 47 SOF (400 mg) +

PEG + RBV

+ RVRPEG + 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

Pati

en

ts (

%)

wit

h S

VR

24

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 & ExperiencedPhase 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 =14Drug DosingSofosbuvir (SOF): 400 mg once dailyRibavirin (RBV) weight-based and divided bid: 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kgPeginterferon 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 wksRBV 12 wks

SOF 12 wksRBV 12 wksPEG wk 1-4

SOF 12 wksRBV 12 wksPEG wk 1-8

SOF 12 wksRBV 12 wksPEG 12 wks

SOF 12 wks SOF 8 wksRBV 8 wksPEG 8 wks



Pa

tie

nts

wit

h S

VR

(%

)

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 NaïvePhase 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)

Pati

en

ts (

%)

wit

h S

VR

12

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)

Pati

en

ts (

%)

wit

h S

VR

12

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 & ExperiencedPhase 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

Pati

en

t (%

) w

ith

SV

R 1

2

12-week Treatment 24-week Treatment

68/73 213/250


VALENCE: Results

VALENCE: SVR12 by Genotype and Prior Treatment Experience


93

85

97 9490

79

0

20

40

60

80

100

Genotype 2 Genotype 3

Pati

en

ts (

%)

wit

h S

VR

12

All Treatment-Naïve Treatment-Experienced

68/73 213/25031/32 37/41 99/105 114/145


Treatment NaïvePhase 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 weeksSVR24

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


Pa

tie

nts

(%

) w

ith

HC

V R

NA

< 1

2 IU

/ml

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


9688

48

96 96

68

0

20

40

60

80

100


Pa

tie

nts

(%

) w

ith

HC

V R

NA

< 1

2 IU

/ml

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*)

Pa

tie

nts

(%

) w

ith

SV

R24

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

Pati

en

ts (

%)

wit

h S

VR

24

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


Thanks

essence of sofosbuvir 400mg

Healthcare

hcv replication

hcv screening

hepatitis c virus hcv

hcvinfected persons

distribution of hcv

endoplasmic reticulum

hepatitis c virus ld

directacting antivirals