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HCV controversyIria Rodríguez Osorio & Álvaro Mena De CeaClinical Virology Group, INIBIC-CHUACInternal Medicine Service, [email protected]@sergas.es
CLINICAL CASE54 yo male. No comorbidities. No chronic treatment.
HCV chronic infection, known since 2004.
Genotype 1 a. HCV RNA: 5.2 log UI/mL. Treatment naive.
Blood test: Hb 14,8 gr/dL, Platelets 140000, AST 102 UI/L, ALT 124 UI/L. VHB, HIV negative. Autoinmune test negative.
Abdominal US: normal.
Fibroscan: 9,6 kPa (IQR 1,4 kPa). F3.
Never had a decompesation episode.
This patient has an HCV chronic infection, G1a, naive, anF3 stage, which would be our treatment options?
Treatment options in Spain TODAY
• IFN based regimen:– Simeprevir + Peg-IFN + RBV– Sofosbuvir + Peg-IFN + RBV
• IFN free regimen:– Sofosbuvir + RBV– Sofosbuvir + Simeprevir ± RBV– Coming soon:
• Daclatasvir + Sofosbuvir ± RBV• Daclatasvir + Simeprevir ± RBV• Sofosbuvir + Ledipasvir ± RBV• 3D ± RBV
o Efficacy on clinical trials (QUEST 1-2).
o Efficacy in real life cohorts.
o Week 4.
o Costs.
IFN regimen based on a PI
SIMEPREVIRP
hase
IIaP
hase
IIb
Pha
se
III
Prior relapser
PROMISE(NCT01281839)
Treatment experienced
Treatment naïve
Treatment-naïve & -experienced
RESTORE: HPC3011 (NCT01567735)
Long term follow up(NCT01349465)
Prior partial & null responder
ATTAIN (NCT01485991)
IFN freeGenotype 4 Other populations
Treatment-naïve & -experienced
C212 HCV/ HIV coinfected
(NCT01479868)
Treatment-naïve & null responder
LEAGUE-1 SMV + DCV
(NCT01628692)
Post-OLT, treatment-naïve & null responder
SMV + DCV ± RBV (NCT01938625)
Treatment-naïve, HCV GT 1b/4/6 and treatment-naïve/experienced
HCV GT1a/b
SMV + IDX719 ± RBV (NCT01852604)
GT 1 or 4 treatment-naïve & experienced
Shorter duration - 12 week study (NCT01846832)
Pbo-experienced prior relapsers, partial responder & null responder
C213 Rollover Study(NCT01323244)
Treatment-naïve & prior relapsers & non responders
OPERA 1 (NCT00561353)
Treatment-naïve & null responder
COSMOS SMV + SOF (NCT01466790)
Treatment-naïve & null responder Non-cirrhotic
OPTIMIST-1HPC3017
(NCT02114177)Treatment-naïve & null responder
Cirrhotic
OPTIMIST-2HPC3018
(NCT02114151)
GT1, treatment-experienced
ASPIRE(NCT00980330)
GT1 treatment-naive
PILLAR(NCT0882908)
Treatment-naïve GT2-6
TMC435-C202 (NCT00812331)
GT1, treatment-naive
QUEST-1/2(NCT01289782 + NCT01290679)
EFFICACY ON CLINICAL TRIALS
0 12 24
SMV 150 mg/d +
PRPR
48 72 Weeks
N= 521
N= 264 PR + placebo PR
PR
Follow-upFollow-up
Follow-up
• Phase 3, randomised, double-blind, placebo-controlled trials: N= 785.
• Randomised by: Subtype and IL28B.
• Primary objetive: SVR12.
• Quest 1 and 2 were similar (design, population included, basal characteristics).
Evidence: QUEST studies
Efficacy by subtype (European population)
EVIDENCE: QUEST 1-2
Jacobson IM, et al. Hepatol 2013;58(Suppl 1):756A-757A (Abstract 1122)
• Efficacy by fibrosis stage (European patients)
8681
71
58
44
25
0
20
40
60
80
100
F0–F2 F3 F4
SV
R1
2(%
)
191/217 64/110 29/36 7/16 10/14 4/16
Adj diff 38.695% CI: 27.2 - 50.0
Adj diff 46.695% CI: 32.5 - 60.8
Adj diff 50.095% CI: 38.2 - 61.8
Foster G et al. EASL 2014. Poster P1127
EVIDENCE: QUEST 1-2
o Efficacy on clinical trials (QUEST 1-2).
o Efficacy in real life cohorts.
o Week 4.
o Costs.
IFN regimen based on a PI
REAL LIFE COHORTS
No data at the Liver Congress of the AASDL 2014.
Coming data at the:
– EASLD 2015, Liver Congress.
– Spanish National Congress of Liver Disease.
o Efficacy on clinical trials (QUEST 1-2).
o Efficacy in real life cohorts.
o Week 4.
o Costs.
IFN regimen based on a PI
WEEK 4
78
12
0
20
40
60
80
100
SMV + PR Pbo + PR
RV
R (
%)
90
0
20
40
60
80
100
RVR patients
SV
R1
2 (
%)
Jacobson IM, et al. Hepatol 2013;58(Suppl 1):756A-757A (Abstract 1122).
WEEK 4
• Predicted value of week 4.
Subtype G1 Polimorfismo Q80K en VHV G1a
Jacobson IM, et al. Hepatol 2013;58(Suppl 1):756A-757A (Abstract 1122)
o Efficacy on clinical trials (QUEST 1-2).
o Efficacy in real life cohorts.
o Week 4.
o Costs.
IFN regimen based on a PI
COSTS
1.000 patients 25 Mil. € 25.000 €
2.000 patients 50 Mil. € 25.000 €
3.000 patients 70 Mil. € 23.300 €
4.000 patients 70 Mil. € 17.500 €
5.000 patients 70 Mil. € 14.000 €
6.000 patients 70 Mil. € 11.600 €
7.000 patients 70 Mil. € 10.000 €
Patients Total cost Cost by patient
100 patients 2,3 Mill. € 23.000 €*
150 patients 3,4 Mill. € 23.000 €*
170 patients 3,9 Mill. € 23.000 €*
200 patients 3,9 Mill. € 19.500 €*
400 patients 3,9 Mill. € 9.750 €*
600 patients 3,9 Mill. € 6.500 €*
1000 patients 3,9 Mill. € 3.900 €*
Patients Total cost Cost by patient
Aproximate cost in Galicia
COSTS
SUMMARY
• IFN based regimen (G1a, Naive, F3): Simeprevir + Peg-IFN + RBV:
– SVR 12w ≅ 80%.
– G1a without Q80K similar SVR rates as G1b ( 82% vs 90%).
– Predicted value of week 4. RVR: 90% achived SVR.
– Costs?
Treatment options in Spain TODAY
• IFN based regimen:– Simeprevir + Peg-IFN + RBV– Sofosbuvir + Peg-IFN + RBV
• IFN free regimen:– Sofosbuvir + RBV– Sofosbuvir + Simeprevir ± RBV– Coming soon:
• Daclatasvir + Sofosbuvir ± RBV• Daclatasvir + Simeprevir ± RBV• Sofosbuvir + Ledipasvir ± RBV• 3D ± RBV
o Efficacy on clinical trials (NEUTRINO).
o Efficacy in real life cohorts (AASLD 2014).
o Interactions.
o Costs.
o Clinical guidelines.
IFN regimen based on SOF
0 12 16 24 36Week
Treatment-Naïve: NEUTRINO
SOF + PEG-IFN + RBV, n=292 SVR12
IFN-CONTAINING
THERAPY
IFN-FREEALL-ORAL THERAPY
No response guided therapy
Historical Control: TVR or BOC + PEG-IFN + RBV
Treatment-Naïve: Study 1910
SOF + PEG-IFN + RBV, n=19 SVR12
Treatment-Naïve: QUANTUM/NIAID SPARE
SOF + RBV, n=159 SVR12
Treatment-Naïve HIV/HCV Co-infection: PHOTON-2
SOF + RBV, n=112 SVR12
Treatment-Experienced: Retreatment of PI Failures
SOF + PEG-IFN + RBV, n=50 SVR12
⸗
SOFOSBUVIR GT 1
NEUTRINO study
12 24
SVR12HCV GT 1Treatment-naïve
n=292
0Study week
SOF 400 mg/day +
PEG-IFN 180 µg/week +
RBV 1000‒1200 mg/day
No response guided therapy
Overall (GT 1, 4, 5, 6)SOF + PEG-IFN + RBV
N=327
Mean age, y (range) 52 (19‒70)
Male, n (%) 209 (64)
Black, n (%) 54 (17)
Hispanic, n (%) 46 (14)
Mean BMI, kg/m2 (range) 29 (18‒56)
IL28B CC, n (%) 95 (29)
GT 1, n (%) 292 (89)
GT 4/5/6, n (%) 35 (11)
Mean baseline HCV RNA, log10 IU/mL (SD) 6.4 (± 0.7)
Cirrhosis, n (%) 54 (17)
GT 1,4,5,6 Treatment-Naïve SOF + PR x 12 Wks
9199 99
0
20
40
60
80
100
On treatment
Pat
ient
s w
ith H
CV
RN
A <
LLO
Q (
%)
90
Post-treatment
Week 12
295/327299/327 321/325 326/327
N Engl J Med 2013;368:1878-87
SOF + PEG-IFN + RBV N=327
Overall safety
AEs, n (%) 310 (95)
Grade 3‒4 AEs, n (%) 48 (15)
Serious AEs, n (%) 4 (1)
Treatment D/C due to AEs, n (%) 5 (<2)
Hematologic abnormalities
Grade 3–4 laboratory abnormality, n (%) 159 (49)
Hemoglobin <10 g/dL, n (%) 74 (23)
Hemoglobin <8.5 g/dL, n (%) 8 (2)
Absolute neutrophil count <750/mm3, n (%) 66 (20)
Platelets <50,000/mm3, n (%) 1 (<1)
• SOF was well tolerated without any additive effects to the expected safety profile of PR
• Most common AEs were fatigue (59%), headache (36%), nausea (34%) and insomnia (25%)
• A total of 5/327 (1.5%) of patients D/C due to an AE
NEUTRINO: Safety summary
N Engl J Med 2013;368:1878-87
o Efficacy on clinical trials (NEUTRINO).
o Efficacy in real life cohorts (AASLD 2014).
o Interactions.
o Costs.
o Clinical guidelines.
IFN regimen based on SOF
Patients in HCV- TARGET 2.0:N= 2330
ITT withSOF+PRN= 402
ITT withSOF+RBV
N= 699
ITT withSOF+SMV
N= 883
ITT withSOF+SMV+RBV
N= 234
TreatedSOF+PRN= 384
TreatedSOF+RBV
N= 667
TreatedSOF+SMV
N= 784
TreatedSOF+SMV+RBV
N= 228
Patients included: Flowchart
SVR4 for 164/200 patients
90
70
85
0
20
40
60
80
100
No cirrosis Cirrosis Global
Jensen DM et al; Safety and Efficacy of Sofosbuvir- Containing Regimens for Hepatitis C: Real-World Experience in a Diverse, Longitudinal Ob servational Cohort
Boston Nov 2014
SVR4 in GT1 treated with PR+SOF
Baseline characteristics
GT 1(n= 669)
SOF + PR x 12s
(44%)
SMV + SOF x 12s
(42%)
SOF + RBV x 24s
(12%)
GT 2(n=197)
SOF + RBV x 12s
(95%)
SOF + PR x 12s
(5%)
SOF + RBV x 24s
(93%)
SOF + PR x 12s
(6%)
GT 3(n=110)
85
91 9289
78
84
65
78
90 93
99
85 8794
80
8790 91 93
79
8992
83
0%
20%
40%
60%
80%
100%
Overall Naive Naive Non-
Cirrhosis
Naive
Cirrhosis
Experienced Exp Non-
Cirrhosis
Exp Cirrhosis PI Failure
SV
R 1
2 (
%)
G1 SOF/PR G1 SOF/SMV±RBV G2
Dieterich et al, Abstract 46Bacon et al., Abstract 975Flamm et al., Abstract 983
REAL LIFE: TRIO network
81
91
81
93
8287
0
20
40
60
80
100
SOF/PR (ITT) SOF/PR (PP)
g1 g1a g1b
169 125 33 150 109 31
SV
R1
2 (
%)
NAÏVE
72
78
71
79
7074
0
20
40
60
80
100
SOF/PR (ITT) SOF/PR (PP)
g1 g1a g1b
125 73 37 115 66 35S
VR
12
(%
)
Dieterich et al; Evaluation of sofosbuvir and simeprevir-based regimens in the TRIO network, AASLD Boston 2014
REAL LIFE: TRIO network GT1TREATMENT EXPERIENCED
NAÏVE
Dieterich et al; Evaluation of sofosbuvir and simeprevir-based regimens in the TRIO network, AASLD Boston 2014
REAL LIFE: TRIO network GT1TREATMENT EXPERIENCED
o Efficacy on clinical trials (NEUTRINO).
o Efficacy in real life cohorts (AASLD 2014).
o Interactions.
o Costs.
o Clinical guidelines.
IFN regimen based on SOF
SOF is activated in hepatocyte
� Hydrolases (CES1, Cat A; HNT1)
� Phosphorylated to active GS-4612003
� Predominant circulating form GS-331007
SOF not metabolised by or inhibits CYP
SOF interacts with P-gp (and BCRP) - Victim
Interaction Potential - WEAK
Mathias A 14th Int Workshop on Clin Pharm of HIV Ther; April 2013; Sofosbuvir USPI.
SOF: Interactions
Drug Interaction Potential of 22 Highly Utilized medications in US Patients
Medication BOC TVR SOF SIM
Zolpidem
Alprazolam
Amlodopine
Prednisone
Tramadol
Codeine
Fluticasone
Methylprednisolone
Escitalopram
Trazodone
Clindamycin
Medication BOC TVR SOF SIM
Diazepam
Sertraline *
Lansoprazole
Clonazepam
Sildenafil
Fluconazole **
Simvastatin
Venlafaxine
Salmeterol
Clarithromycin **
Tacrolimus
Modified from Lauffenburger JC et al. Eur J Gastro & Hepatology 2014)
* No PK interaction but sertraline should not be used in patients with severe hepatic impairment;
** Not recommended – increased SIM expected.
o Efficacy on clinical trials (NEUTRINO).
o Efficacy in real life cohorts (AASLD 2014).
o Interactions.
o Adverse events & Costs.
o Clinical guidelines.
IFN regimen based on SOF
REAL LIFE: ADVERSE EVENTS
Jensen DM et al; Safety and Efficacy of Sofosbuvir- Containing Regimens for Hepatitis C: Real-World Experience in a Diverse, Longitudinal Ob servational Cohort
Boston Nov 2014
Costs: Spanish National Health System
o SOF 12w: 24,531 €
o PR+SOF 12w: 25,571 €
o PR+SIM 24w: 27,700 €
o SIM+SOF 12w: 50,191 €
o Efficacy on clinical trials (NEUTRINO).
o Efficacy in real life cohorts (AASLD 2014).
o Interactions.
o Adverse events & Costs.
o Clinical guidelines.
IFN regimen based on SOF
• IFN based regimen: SOF + Peg-IFN + RBV:
– SVR 12w: 82% (ITT), 92% (PP) in real life.
– Costs.
– Less IFN exposure.
SUMMARY
Treatment options in Spain TODAY
• IFN based regimen:– Simeprevir + Peg-IFN + RBV– Sofosbuvir + Peg-IFN + RBV
• IFN free regimen:– Sofosbuvir + RBV– Sofosbuvir + Simeprevir ± RBV– Coming soon:
• Daclatasvir + Sofosbuvir ± RBV• Daclatasvir + Simeprevir ± RBV• Sofosbuvir + Ledipasvir ± RBV• 3D ± RBV
o Efficacy on clinical trials (QUANTUM/NIAID SPARE).
o Efficacy in real life cohorts (AASLD 2014).
o Adverse effects
IFN free regimen: SOF+RBV
0 12 16 24 36Week
Treatment-Naïve: NEUTRINO
SOF + PEG-IFN + RBV, n=292 SVR12
IFN-CONTAINING
THERAPY
IFN-FREEALL-ORAL THERAPY
No response guided therapy
Historical Control: TVR or BOC + PEG-IFN + RBV
Treatment-Naïve: Study 1910
SOF + PEG-IFN + RBV, n=19 SVR12
Treatment-Naïve: QUANTUM/NIAID SPARE
SOF + RBV, n=159 SVR12
Treatment-Naïve HIV/HCV Co-infection: PHOTON-2
SOF + RBV, n=112 SVR12
Treatment-Experienced: Retreatment of PI Failures
SOF + PEG-IFN + RBV, n=50 SVR12
⸗
SOFOSBUVIR GT 1
QUANTUM: Patients with GT 1(SVR12)
Lalezari JP, et al. EASL. 2013; Abstract 845
5347
66
0
20
40
60
80
100
SOF + RBV x 12 Wks SOF + RBV x 24 Wks SOF + RBVRetreatment x 24 Wks
Pat
ient
s (%
) w
ith S
VR
12
10/19 9/19 69/105
QUANTUM: Patients with GT 1(SVR12)
Lalezari JP, et al. EASL. 2013; Abstract 845
5347
71
50 50 48
0
20
40
60
80
100
SOF + RBV x 12 Wks SOF + RBV x 24 Wks SOF + RBVRetreatment x 24 Wks
Pat
ient
s (%
) w
ith S
VR
12
Genotype 1a Genotype 1b
8/15 2/4 7/15 2/4 57/80 12/25
NIAID SPARE: Difficult-to-Cure HCV GT 1 naïve Patients
Osinusi A, et al. JAMA 2013;310:804–11
• In this difficult-to-cure treatment-naïve, HCV GT 1 population (n=60),
an IFN-free regimen of SOF + RBV was well-tolerated and effective in achieving SVR
– Full dose RBV: SVR12 of 68% (ITT), 71% (mITT)
– Low dose RBV: SVR12 of 48% (ITT), 55% (mITT)
– There were no safety signals or drug-related discontinuations in this study
Part 1 Part 2
QUANTUM/NIAID SPARE: Patients with GT
8/15 2/4 7/15 2/4 57/80 12/25
• SOF + RBV resulted in rapid suppression of HCV RNA with ≥98% RVR rate
• In the SOF+RBV x12w 56% (QUANTUM) and x24w 52% (QUANTUM) and 68% (NIAID SPARE) achieved SVR12.
• Well tolerated, with no safety signals noted• 2% D/C due to AE.• For those who relapsed, no resistance mutations seen.
o Efficacy on clinical trials (QUANTUM/NIAID SPARE).
o Efficacy in real life cohorts (AASLD 2014).
o Adverse effects.
IFN free regimen: SOF+RBV
REAL LIFE: SOF+RBV
77
50
85
78
0
20
40
60
80
100
SOF/PR SOF/R SOF/PR SOF/R
SV
R1
2 (
%)
295 14
ITT PP
266 9
Dieterich et al; Evaluation of sofosbuvir and simeprevir-based regimens
in the TRIO network, AASLD Boston 2014
o Efficacy on clinical trials (QUANTUM/NIAID SPARE).
o Efficacy in real life cohorts (AASLD 2014).
o Adverse effects.
IFN free regimen: SOF+RBV
REAL LIFE: SOF+RBV
Jensen DM et al; Safety and Efficacy of Sofosbuvir- Containing Regimens for Hepatitis C: Real-World Experience in a Diverse, Longitudinal Ob servational Cohort
Boston Nov 2014
• IFN free regimen: SOF + RBV:
– SVR 12w: 50-60%.
– Adverse events common, but none severe or moderate.
– For those who relapsed, no resistance mutations seen.
SUMMARY
Treatment options in Spain TODAY
• IFN based regimen:– Simeprevir + Peg-IFN + RBV– Sofosbuvir + Peg-IFN + RBV
• IFN free regimen:– Sofosbuvir + RBV– Sofosbuvir + Simeprevir ± RBV– Coming soon:
• Daclatasvir + Sofosbuvir ± RBV• Daclatasvir + Simeprevir ± RBV• Sofosbuvir + Ledipasvir ± RBV• 3D ± RBV
o Efficacy on clinical trials (COSMOS).
o Efficacy in real life cohorts (AASLD 2014).
o Adverse effects
o Cost
IFN free regimen: Simeprevir + Sofosbuvir
SIMEPREVIRP
hase
IIaP
hase
IIb
Pha
se
III
Prior relapser
PROMISE(NCT01281839)
Treatment experienced
Treatment naïve
Treatment-naïve & -experienced
RESTORE: HPC3011 (NCT01567735)
Long term follow up(NCT01349465)
Prior partial & null responder
ATTAIN (NCT01485991)
IFN freeGenotype 4 Other populations
Treatment-naïve & -experienced
C212 HCV/ HIV coinfected
(NCT01479868)
Treatment-naïve & null responder
LEAGUE-1 SMV + DCV
(NCT01628692)
Post-OLT, treatment-naïve & null responder
SMV + DCV ± RBV (NCT01938625)
Treatment-naïve, HCV GT 1b/4/6 and treatment-naïve/experienced
HCV GT1a/b
SMV + IDX719 ± RBV (NCT01852604)
GT 1 or 4 treatment-naïve & experienced
Shorter duration - 12 week study (NCT01846832)
Pbo-experienced prior relapsers, partial responder & null responder
C213 Rollover Study(NCT01323244)
Treatment-naïve & prior relapsers & non responders
OPERA 1 (NCT00561353)
Treatment-naïve & null responder
COSMOS SMV + SOF (NCT01466790)
Treatment-naïve & null responder Non-cirrhotic
OPTIMIST-1HPC3017
(NCT02114177)Treatment-naïve & null responder
Cirrhotic
OPTIMIST-2HPC3018
(NCT02114151)
GT1, treatment-experienced
ASPIRE(NCT00980330)
GT1 treatment-naive
PILLAR(NCT0882908)
Treatment-naïve GT2-6
TMC435-C202 (NCT00812331)
GT1, treatment-naive
QUEST-1/2(NCT01289782 + NCT01290679)
EVIDENCE: COSMOSSMV + SOF + RBV Follow up
0 4 1
2
2
4
3
6
4
8
Arm 1
Week
SMV + SOF
SMV + SOF
+ RBV
SMV + SOF
Follow up
Follow up
Follow up
Arm 2
Arm 3
Arm 4
• Phase 2a, multicentric, randomised and open trial: n= 107.
– Cohort 1 (n=80): Null responders and F0-F2.
– Cohort 2 (n=87): Treatment naive or previous null responders, F3-F4.
93 93
0
20
40
60
80
100
SMV + SOF +
RBV
SMV + SOF
SVR in treatment naive and null, F3-F4
High efficiency (92% SVR) of an IFN free regimen: Simeprevir+Sofosbuvir±ribavirin. 12 weeks regimen. Regardless subtype of G1, Q80K polimorphism, fibrosis stage, IL28B
or previous response to treatment.
EVIDENCE: COSMOS
o Efficacy on clinical trials (COSMOS).
o Efficacy in real life cohorts (AASLD 2014).
o Adverse effects
o Cost
IFN free regimen: Simeprevir + Sofosbuvir
Longitudinal, observational study of the clinical practice. > 18 yo on HCV treatment.> 4700 patients included.
Jensen DM et al; Safety and Efficacy of Sofosbuvir- Containing Regimens for Hepatitis C: Real-World Experience in a Diverse, Lo ngitudinal Observational Cohort
Boston Nov 2014
REAL LIFE: TARGET
REAL LIFE: TARGET
> 1000 Patients have been treated with SMV/SOF o SMV/SOF/RBV
HCV- TARGET 2.0:N= 2330
ITT conSOF+PRN= 402
ITT conSOF+RBV
N= 699
ITT conSOF+SMV
N= 883
ITT conSOF+SMV+RBV
N= 234
TreatedSOF+PRN= 384
TreatedSOF+RBV
N= 667
TreatedSOF+SMV
N= 784
TreatedSOF+SMV+RBV
N= 228
REAL LIFE: TARGET
8695
0
20
40
60
80
100
Genotipo 1a Genotipo 1b
SV
R4
(%
)
154/180 88/93
8087 88
94
8288 87
93
0
20
40
60
80
100
1a concirrosis
1a sincirrosis
1b concirrosis
1b sincirrosis
Sin RBV
Con RBV
SOF + SMV ± RBV by subtype
Dieterich et al; Evaluation of sofosbuvir and simeprevir-based regimens in the TRIO network, AASLD Boston 2014
Genotipo 1(n= 669)
SOF + PR x 12s(44%)
SMV + SOF x 12s(42%)
SOF + RBV x 24s(12%)
Genotipo 2(n=197)
SOF + RBV x 12s(95%)
SOF + PR x 12s(5%)
Genotipo 3(n=110)
SOF + RBV x 24s(93%)
SOF + PR x 12s(6%)
REAL LIFE: TRIO network
83
93
80
929297
0
20
40
60
80
100
SIM/SOF± RBV (ITT) SIM/SOF± RBV (ITT)
(PP)
g1 g1a g1b
75
8588
99
0
20
40
60
80
100
SIM/SOF± RBV (ITT) SIM/SOF± RBV (PP)
Cirrosis No cirrosis
ITT PPITT PP
REAL LIFE: TRIO network
PACIENTES NAÏVE
o Efficacy on clinical trials (COSMOS).
o Efficacy in real life cohorts (AASLD 2014).
o Adverse effects
o Cost
IFN free regimen: Simeprevir + Sofosbuvir
ADVERSE EVENTS
Patients, %
12 weeks 24 weeks
SMV + SOF + RBV
(n=54)
SMV + SOF
(n=28)
SMV + SOF + RBV
(n=54)
SMV + SOF
(n=31)
Any AE 46 (85.2) 20 (71.4) 50 (92.6) 28 (90.3)
Grade 3-4 AEs 6 (11.1) 1 (3.6) 4 (7.4) 4 (12.9)
SAEs* 0 0 2 (3.7) 1 (3.2)
AEs leading to permanent
treatment discontinuation**
0 0 2 (3.7) 2 (6.5)
Deaths during treatment† 0 0 1 (1.9) 0
Jacobson IM, et al. AASLD 2013. Oral Presentation LB-3
*Serious AEs: anemia, injury, retinal tear; **AEs leading to discontinuation: injury, increased blood creatine phosphokinase , aggression and renal failure (1 incidence of each); †Death during treatment was due to injury;
Cohort 1 and Cohort 2 of COSMOS study
o Efficacy on clinical trials (COSMOS).
o Efficacy in real life cohorts (AASLD 2014).
o Adverse effects
o Cost
IFN free regimen: Simeprevir + Sofosbuvir
• IFN free regimen (G1a, Naive, F3): Simeprevir + Sofosbuvir ± RBV:
– SVR 12w: >85%.
– SVR achived regardless subtype, Q80K polimorphism, ILB28, fibrosis stage and previous response to treatment.
– Adverse events comon, but none severe or moderate.
– A cost-effective regimen.
SUMMARY