A New Treatment Algorithm in
th Era
the
E off DAAs
DAA
Treatment Algorithms Differ Between
T l
i and
d Boceprevir
B
i
Telaprevir
•
Boceprevir:
– Treatment-naïve patients
– Previous
P i
partial
ti l responders
d
or relapsers
l
– Null responders
• Telaprevir:
– Treatment-naïve and prior relapse patients
– Prior p
partial and null responders
p
• Both telaprevir and boceprevir must be
used in combination with PEG-IFN and RBV
to minimize viral resistance
Boceprevir: Treatment-Naïve Patients–
Rapid Responder
Chronic HCV Genotype 1, boceprevir 800 mg (four 200 mg capsules) 3 times daily
(7-9 hours apart) with food
Treatment
Decision
Points
Initiate
antiviral
treatment
0
4
8
12
End of 8
Weeks
PEGIFN+RBV
End of 12
Weeks
24
28
36
48
End of 24
Weeks
Boceprevir + PEG-IFN + RBV
8-week HCV-RNA
Responseguided
therapy
24-week HCV-RNA
Continue Tx
U d
Undetectable
bl
U d
Undetectable
bl
Treatment complete
p
at 28 weeks
For boceprevir
boceprevir, HCV
HCV-RNA
RNA at wk 8 and wk 24 determine duration of therapy
Boceprevir capsules [package insert]. 2011.
Boceprevir: Treatment-Naïve Patients–
Slow Responder
Chronic HCV Genotype
y 1, boceprevir 800 mg
g ((four 200 mg
g capsules)) 3 times daily
y
(7-9 hours apart) with food
Treatment
Decision
Points
Initiate
antiviral
treatment
0
4
8
End of 8
Weeks
PEGIFN+RBV
12
End of 12
Weeks
24
28
End of 24
Weeks
36
48
End
of 48
Wks
PEGIFN+
RBV
Boceprevir + PEG-IFN + RBV
24-week HCV-RNA
8-week HCV-RNA
Stop BOC at week 36
Responseguided
therapy
Continue Tx
D
Detectable
bl
U d
Undetectable
bl
Treatment
complete at
48 weeks
For boceprevir
boceprevir, HCV
HCV-RNA
RNA at wk 8 and wk 24 determine duration of therapy
Boceprevir capsules [package insert]. 2011.
Boceprevir: Treatment-Naïve Patients–
Poorly IFN Responsive
Chronic HCV Genotype 1, boceprevir 800 mg (four 200 mg capsules) 3 times daily
(7-9 hours apart) with food
Treatment
Decision
Points
Initiate
antiviral
treatment
0
4
8
End of 8
Weeks
PEGIFN+RBV
Poorly IFN
responsive*
12
End of 12
Weeks
24
End of 24
Weeks
28
36
48
End
of 48
Wks
Boceprevir + PEG-IFN + RBV
Triple therapy
for 44 weeks
< 1 log10 IU/mL
decline in viral
load at Wk 4
Treatment
complete at
48 weeks
*Standard stopping rules assessed at weeks 12 and 24 still apply
Assess interferon responsiveness after lead-in
lead in with PEG
PEG-IFN/RBV
IFN/RBV
Boceprevir capsules [package insert]. 2011.
Telaprevir: Treatment-Naïve and Prior Relapse
Patients–Rapid Responder
Chronic HCV Genotype 1, telaprevir 750 mg (two 375 mg tablets) orally 3 times daily
(7-9 hours apart) with food (~ 20 gm fat †)
Treatment
Decision
Points
0
Initiate
antiviral
treatment
4
End of 4
Weeks
12
End of 12
Weeks
Telaprevir + PEG-IFN + RBV
4-week HCV-RNA
24
End of 24
Weeks
PEG-IFN + RBV
12-week HCV-RNA
eRVR
undetectable
at weeks 4 and 12
Responseguided
therapy
food within 30 min prior to dose
~20 gm fat: Bagel w/ cream cheese; 1/2 cup nuts; 3 tbsp
peanut butter; 1 cup ice cream; 2 oz American or cheddar
cheese; 2 oz potato chips; 1/2 cup trail mix
mix.
48
End of 48
Weeks
PEG-IFN + RBV
Treatment
complete
at 24 weeks
Tx-naïve w/
cirrhosis‡
†Ingest
Treat for
48 weeks
‡Treatment-naïve
patients with cirrhosis who have
undetectable HCV-RNA at weeks 4 and 12 may benefit
from an additional 36 weeks of PEG-IFN/RBV
(48 weeks total)
For telaprevir, HCV-RNA at wk 4 and wk 12 determine duration of therapy
Telaprevir tablets [package insert]. 2011.
Telaprevir: Treatment-Naïve and Prior Relapse
Patients–Slow Responder
Chronic HCV Genotype 1, telaprevir 750 mg (two 375 mg tablets) orally 3 times daily
(7-9 hours apart) with food (~ 20 gm fat)
Treatment
Decision
Points
Initiate
antiviral
treatment
0
4
End of 4
Weeks
12
End of 12
Weeks
Telaprevir + PEG-IFN + RBV
4-week HCV-RNA
24
End of 24
Weeks
PEG-IFN + RBV
End of 48
Weeks
PEG-IFN + RBV
12-week HCV-RNA
Detectable
≤ 1000 IU/mL at
weeks 4 and/or
12
Responseguided
therapy
48
Treatment
complete
at 48 weeks
For telaprevir, HCV-RNA at wk 4 and wk 12 determine duration of therapy
Telaprevir tablets [package insert]. 2011.
Boceprevir: Previous Partial Responders or
Relapsers–Rapid Responder
Chronic HCV Genotype 1, boceprevir 800 mg (four 200 mg capsules) 3 times daily
(7-9 hours apart) with food
Treatment
Decision
Points
Initiate
antiviral
treatment
4
8
End of 8
Weeks
PEGIFN+RBV
12
End of 12
Weeks
24
28
36
48
End of 24
Weeks
Boceprevir + PEG-IFN + RBV
8-week HCV-RNA
Responseguided
therapy
24-week HCV-RNA
Continue Tx
U d
Undetectable
bl
U d
Undetectable
bl
Treatment complete
at 36 weeks
For boceprevir
boceprevir, HCV
HCV-RNA
RNA at wk 8 and wk 24 determine duration of therapy
Boceprevir capsules [package insert]. 2011.
Boceprevir: Previous Partial Responders or
Relapsers–Slow Responder
Chronic HCV Genotype 1, boceprevir 800 mg (four 200 mg capsules) 3 times daily
(7-9 hours apart) with food
Treatment
Decision
Points
Initiate
antiviral
treatment
0
4
8
End of 8
Weeks
PEGIFN+RBV
12
End of 12
Weeks
24
28
End of 24
Weeks
36
48
End
of 48
Wks
PEGIFN+
RBV
Boceprevir + PEG-IFN + RBV
24-week HCV-RNA
8-week HCV-RNA
Stop BOC at week 36
Responseguided
therapy
Continue Tx
D
Detectable
bl
U d
Undetectable
bl
Treatment
complete at
48 weeks
For boceprevir
boceprevir, HCV
HCV-RNA
RNA at wk 8 and wk 24 determine duration of therapy
Boceprevir capsules [package insert]. 2011.
Boceprevir: Null Responders and Cirrhotics
Chronic HCV Genotype 1, boceprevir 800 mg (four 200 mg capsules) 3 times daily
(7 9 h
t) with
ith food
f d
(7-9
hours apart)
Treatment
Decision
Points
0
Initiate
antiviral
treatment
4
8
End of 8
Weeks
PEGIFN+RBV
12
End of 12
Weeks
24
End of 24
Weeks
28
36
48
End
of 48
Wks
Boceprevir + PEG-IFN + RBV
Treatment
complete at
48 weeks
Prior null
responders
Triple therapy
for 44 weeks
Patients with
compensated
cirrhosis
Treatment
complete
l t att
48 weeks
RGT was not studied in patients with < 2 log10 HCV-RNA
HCV RNA decline by week 12
during prior therapy with PEG-IFN/RBV
Boceprevir capsules [package insert]. 2011.
Telaprevir: Treatment of Prior Partial and Null Responders
Chronic HCV Genotype 1, telaprevir 750 mg (two 375 mg tablets) orally 3 times daily
(7 9 h
t) with
ith ffood
d (~20
( 20 gm fat)
f t)
(7-9
hours apart)
Treatment
Decision
Points
Initiate
antiviral
treatment
0
4
End of 4
Weeks
12
End of 12
Weeks
Telaprevir + PEG-IFN + RBV
24
End of 24
Weeks
End of 48
Weeks
PEG-IFN + RBV
Triple therapy
for 12 weeks
No RGT in partial and null responder patients with TVR
Telaprevir tablets [package insert]. 2011.
48
Treatment
complete
at 48 weeks
Boceprevir: Stopping Rules
Treatment
Decision
Points
Initiate
antiviral
treatment
0
4
8
12
End of 8
Weeks
PEGIFN+RBV
24
End of 12
Weeks
28
End of 24
Weeks
Stopping
Rules
Apply to all
patients
≥ 100 IU/mL
Treatment
failure
Stop
Boceprevir capsules [package insert]. 2011.
48
End
of 48
Wks
BOC ± PEGIFN+ RBV
Boceprevir + PEG-IFN + RBV
12-week
HCV-RNA
36
24-week
HCV-RNA
Detectable
Treatment
failure
Stop
Telaprevir: Stopping Rules
Treatment
Decision
Points
Initiate
antiviral
treatment
Stopping
Rules
0
4
End of 4
Weeks
12
End of 12
Weeks
Telaprevir + PEG-IFN + RBV
24
End of 24
Weeks
PEG-IFN + RBV
4
4-week
k
HCV-RNA
12
12-week
k
HCV-RNA
24
24-week
k
HCV-RNA
> 1000 IU/mL
> 1000 IU/mL
Detectable
Treatment
failure
Treatment
failure
Treatment
failure
Stop
Stop
Stop
Apply to all
patients
Telaprevir tablets [package insert]. 2011.
48
End of 48
Weeks
Telaprevir Futility Rule of > 1000 IU/mL at Week 4
Identified and Predicted Patients Unlikely to Achieve
SVR
HCV RNA profiles in patients with HCV RNA > 1000 IU/mL at week 4
• 23/25 patients with HCV RNA levels > 1000 IU/mL at week 4 reached their HCV RNA nadir prior
to week 4, typically by week 2, with subsequent increase in HCV RNA levels by week 4
• No p
patient with HCV RNA > 1000 IU/mL at week 4 attained SVR despite
p continued PEG-IFN/RBV
• In 92%, HCV RNA already was increasing from HCV RNA nadir by week 4
Jacobson IM, et al. Presented at: EASL: The International Liver Congress 2012; April 18-22,
2012; Barcelona, Spain. Oral Presentation 55.
Key Treatment Differences
Telaprevir
Boceprevir
Simultaneous start of triple therapy
Yes
No
Lead-in of PEG-IFN/RBV x 4 weeks
No
Yes
Yes (24 weeks)
Yes (28 weeks)
Response-guided therapy—
experienced
Yes, prior relapse
patients only (24
weeks))
Yes, previous partial
responders or
relapsers
p
(36
( weeks))
Key decision points for HCV-RNA
Week 4, week 12
Week 8, week 24
Week 4 or 12:
> 1000 IU/mL
Week 24: Detectable
Week 12: ≥ 100 IU/mL
Week 24: Detectable
Response guided therapy—naïve
Response-guided
therapy naïve
Stopping rules
((HCV-RNA))
Telaprevir tablets [package insert]. 2011.
Boceprevir capsules [package insert]. 2011.
FAQs
• Can I stop PEG-IFN and RBV and continue PI?
– No, PIs should never be used as monotherapy.
• Can I stop
p RBV and continue PEG-IFN + PI?
– No.
• What happens if I continue triple therapy when
HCV-RNA levels remain high?
– Stopping
St
i therapy
th
when
h ttreatment
t
t response is
i poor
decreases the chance of a resistant virus.
• Can I switch from telaprevir to boceprevir (or the
reverse) if viral breakthrough occurs?
– No, resistant variants are cross-resistant to both
medications.