On October 10,
2014, FDA
approved HARVONI
a fixed-dose
combination
tablet of
ledipasvir 90
mg, a hepatitis
C virus (HCV)
NS5A inhibitor,
and sofosbuvir
400 mg, an HCV
nucleotide
analog NS5B
polymerase
inhibitor.
Harvoni is
indicated for
the treatment of
chronic
hepatitis C (CHC)
genotype 1
infection in
adults. HARVONI
is the first
combination pill
approved to
treat chronic
HCV genotype 1
infection.
HARVONI is also
the first
approved regimen
that does not
require
administration
with interferon
or ribavirin,
two FDA-approved
drugs also used
to treat HCV
infection.
Dosage
and
Administration:
The recommended
dosage of
HARVONI is one
tablet taken
orally once
daily with or
without food.
Recommended
Treatment
Duration for
HARVONI
in
Patients with
CHC
Genotype 1
Patient
Population |
Recommended
Treatment
Duration |
Treatment-naïve
with or
without
cirrhosis |
12
weeks* |
Treatment-experienced**
without
cirrhosis |
12 weeks |
Treatment-experienced**
with
cirrhosis |
24 weeks |
* HARVONI
for 8 weeks can
be considered in
treatment-naïve
patients without
cirrhosis who
have
pre-treatment
HCV RNA less
than 6 million
IU/mL [see
Clinical Studies
(14)].
**
Treatment-experienced
patients who
have failed
treatment with
either
peginterferon
alfa + ribavirin
or an HCV
protease
inhibitor +
peginterferon
alfa +
ribavirin.
No dosage
adjustment of
HARVONI is
required for
patients with
mild or moderate
renal
impairment. No
dose
recommendation
can be given for
patients with
severe renal
impairment
(estimated
Glomerular
Filtration Rate
[eGFR]
<30 mL/min/1.73m2)
or with end
stage renal
disease (ESRD)
due to higher
exposures (up to
20-fold) of the
predominant
sofosbuvir
metabolite.
No dosage
adjustment of
HARVONI is
required for
patients with
mild, moderate,
or severe
hepatic
impairment
(Child-Pugh
Class A, B, or
C). Safety and
efficacy of
HARVONI have not
been established
in patients with
decompensated
cirrhosis.
WARNINGS
AND PRECAUTIONS
Risk
of Reduced
Therapeutic
Effect Due to
P-gp Inducers
The concomitant
use of HARVONI
and P-gp
inducers (e.g.,
rifampin, St.
John’s wort) may
significantly
decrease
ledipasvir and
sofosbuvir
plasma
concentrations
and may lead to
a reduced
therapeutic
effect of
HARVONI.
Therefore, the
use of HARVONI
with P-gp
inducers (e.g.,
rifampin or St.
John’s wort) is
not recommended
Related Products
Not Recommended
The use of
HARVONI with
other products
containing
sofosbuvir
(SOVALDI®) is
not recommended
Data to
Support
Approval:
Harvoni’s
efficacy was
evaluated in
three clinical
trials enrolling
1,518 subjects
who had not
previously
received
treatment for
their infection
(treatment-naive)
or had not
responded to
previous
treatment
(treatment-experienced),
including
subjects with
cirrhosis.
Subjects were
randomly
assigned to
receive Harvoni
with or without
ribavirin. The
trials were
designed to
measure whether
the hepatitis C
virus was no
longer detected
in the blood at
least 12 weeks
after finishing
treatment
(sustained
virologic
response, or
SVR), indicating
that a subject’s
HCV infection
has been cured.
See Clinical
Studies below
for additional
details.
ADVERSE
REACTIONS
The safety
assessment of
HARVONI was
based on pooled
data from three
Phase 3 clinical
trials of
subjects with
genotype 1
chronic
hepatitis C
(CHC) with
compensated
liver disease
(with and
without
cirrhosis)
including 215,
539, and 326
subjects who
received HARVONI
for 8, 12 and 24
weeks,
respectively.
The most common
adverse
reactions (≥10%)
were fatigue and
headache in
subjects treated
with 8, 12, or
24 weeks of
HARVONI.
The Table
below lists
adverse
reactions
(adverse events
assessed as
causally related
by the
investigator,
all grades)
observed in ≥5%
of subjects
receiving 8, 12,
or 24 weeks
treatment with
HARVONI in
clinical trials.
Themajority of
adverse
reactions
presented in
Table 2 occurred
at severity of
grade 1. The
side-by-side
tabulation is to
simplify
presentation;
direct
comparison
across trials
should not be
made due to
differing trial
designs.
Table
2 Adverse
Reactions (All
Grades) Reported
in ≥5% of
Subjects
Receiving 8, 12,
or 24 Weeks of
Treatment with
HARVONI
|
HARVONI
8 weeks |
HARVONI
12
weeks |
HARVONI
24
weeks |
|
N=215 |
N=539 |
N=326 |
Fatigue |
16% |
13% |
18% |
Headache |
11% |
14% |
17% |
Nausea |
6% |
7% |
9% |
Diarrhea |
4% |
3% |
7% |
Insomnia |
3% |
5% |
6% |
Laboratory
Abnormalities
Bilirubin
Elevations:
Bilirubin
elevations of
greater than
1.5xULN were
observed in 3%,
<1%, and 2% of
subjects treated
with HARVONI for
8, 12, and 24
weeks,
respectively.
Lipase
Elevations:
Transient,
asymptomatic
lipase
elevations of
greater than
3xULN were
observed in <1%,
2%, and 3% of
subjects treated
with HARVONI for
8, 12, and 24
weeks,
respectively.
Creatine
Kinase:
Creatine kinase
was not assessed
in Phase 3
trials of
HARVONI.
Isolated,
asymptomatic
creatine kinase
elevations
(Grade 3 or 4)
have been
previously
reported in
subjects treated
with sofosbuvir
in combination
with ribavirin
or
peginterferon/ribavirin
in other
clinical trials.
DRUG
INTERACTIONS
Ledipasvir is an
inhibitor of the
drug
transporters
P-gp and breast
cancer
resistance
protein (BCRP)
and may increase
intestinal
absorption of
coadministered
substrates for
these
transporters.
Ledipasvir and
sofosbuvir are
substrates of
drug
transporters
P-gp and BCRP
while GS-331007
is not. P-gp
inducers (e.g.,
rifampin or St.
John’s wort) may
decrease
ledipasvir and
sofosbuvir
plasma
concentrations,
leading to
reduced
therapeutic
effect of
HARVONI, and the
use with P-gp
inducers is not
recommended with
HARVONI.
The Table below
provides a
listing of
established or
potentially
clinically
significant drug
interactions.
The drug
interactions
described are
based on studies
conducted with
either HARVONI,
the components
of HARVONI
(ledipasvir and
sofosbuvir) as
individual
agents, or are
predicted drug
interactions
that may occur
with HARVONI.
Potentially
Significant Drug
Interactions:
Alteration in
Dose or Regimen
May Be
Recommended
Based on Drug
Interaction
Studies or
Predicted
Interactiona
Concomitant
Drug
Class:
Drug
Name |
Effect
on
Concentrationb |
Clinical
Comment |
Acid
Reducing
Agents: |
↓
ledipasvir |
Ledipasvir
solubility
decreases
as pH
increases.
Drugs
that
increase
gastric
pH are
expected
to
decrease
concentration
of
ledipasvir. |
Antacids
(e.g.,
aluminum
and
magnesium
hydroxide) |
It is
recommended
to
separate
antacid
and
HARVONI
administration
by 4
hours. |
H2-receptor
antagonistsc
(e.g.,
famotidine) |
H2-receptor
antagonists
may be
administered
simultaneously
with or
12 hours
apart
from
HARVONI
at a
dose
that
does not
exceed
doses
comparable
to
famotidine
40 mg
twice
daily. |
Proton-pump
inhibitorsc
(e.g.,
omeprazole) |
Proton-pump
inhibitor
doses
comparable
to
omeprazole
20 mg or
lower
can be
administered
simultaneously
with
HARVONI
under
fasted
conditions. |
Antiarrhythmics:
digoxin |
↑
digoxin |
Coadministration
of
HARVONI
with
digoxin
may
increase
the
concentration
of
digoxin.
Therapeutic
concentration
monitoring
of
digoxin
is
recommended
when
coadministered
with
HARVONI. |
Anticonvulsants:
carbamazepine
phenytoin
phenobarbital
oxcarbazepine |
↓
ledipasvir
↓
sofosbuvir
↓
GS-331007 |
Coadministration
of
HARVONI
with
carbamazepine,
phenytoin,
phenobarbital,
or
oxcarbazepine
is
expected
to
decrease
the
concentration
of
ledipasvir
and
sofosbuvir,
leading
to
reduced
therapeutic
effect
of
HARVONI.
Coadministration
is not
recommended. |
Antimycobacterials:
rifabutin
rifampinc
rifapentine |
↓
ledipasvir
↓
sofosbuvir
↓
GS-331007 |
Coadministration
of
HARVONI
with
rifabutin
or
rifapentine
is
expected
to
decrease
the
concentration
of
ledipasvir
and
sofosbuvir,
leading
to
reduced
therapeutic
effect
of
HARVONI.
Coadministration
is not
recommended.
Coadministration
of
HARVONI
with
rifampin,
a P-gp
inducer,
is not
recommended
[see
Warnings
and
Precautions
(5.1)]. |
HIV
Antiretrovirals: |
efavirenz,
emtricitabine,
tenofovir
disoproxil
fumarate
(DF) |
↑
tenofovir |
Monitor
for
tenofovir-associated
adverse
reactions
in
patients
receiving
HARVONI
concomitantly
with the
combination
of
efavirenz,
emtricitabine
and
tenofovir
DF.
Refer to
VIREAD,
TRUVADA,
or
ATRIPLA
prescribing
information
for
recommendations
on renal
monitoring. |
Regimens
containing
tenofovir
DF and a
HIV
protease
inhibitor/ritonavir
-
atazanavir/ritonavir
+
emtricitabine/tenofovir
DFc
-
darunavir/ritonavir
+
emtricitabine/tenofovir
DFc
-
lopinavir/ritonavir
+
emtricitabine/tenofovir
DF
|
↑
tenofovir |
The
safety
of
increased
tenofovir
concentrations
in the
setting
of
HARVONI
and a
HIV
protease
inhibitor/ritonavir
has not
been
established.
Consider
alternative
HCV or
antiretroviral
therapy
to avoid
increases
in
tenofovir
exposures.
If
coadministration
is
necessary,
monitor
for
tenofovir-associated
adverse
reactions.
Refer to
VIREAD
or
TRUVADA
prescribing
information
for
recommendations
on renal
monitoring. |
elvitegravir,
cobicistat,
emtricitabine,
tenofovir
DF |
↑
tenofovir |
The
safety
of
increased
tenofovir
concentrations
in the
setting
of
HARVONI
and the
combination
of
elvitegravir,
cobicistat,
emtricitabine
and
tenofovir
DF has
not been
established.
Coadministration
is not
recommended. |
tipranavir/ritonavir |
↓
ledipasvir
↓
sofosbuvir
↓
GS-331007 |
Coadministration
of
HARVONI
with
tipranavir/ritonavir
is
expected
to
decrease
the
concentration
of
ledipasvir
and
sofosbuvir,
leading
to
reduced
therapeutic
effect
of
HARVONI.
Coadministration
is not
recommended. |
HCV
Products:
simeprevirc |
↑
ledipasvir
↑
simeprevir |
Concentrations
of
ledipasvir
and
simeprevir
are
increased
when
simeprevir
is
coadministered
with
ledipasvir.
Coadministration
of
HARVONI
with
simeprevir
is not
recommended. |
Herbal
Supplements:
St.
John’s
wort
(Hypericum
perforatum) |
↓
ledipasvir
↓
sofosbuvir
↓
GS-331007 |
Coadministration
of
HARVONI
with St.
John’s
wort, a
P-gp
inducer
is not
recommended
[see
Warnings
and
Precautions
(5.1)]. |
HMG-CoA
Reductase
Inhibitors:
rosuvastatin |
↑
rosuvastatin |
Coadministration
of
HARVONI
with
rosuvastatin
may
significantly
increase
the
concentration
of
rosuvastatin
which is
associated
with
increased
risk of
myopathy,
including
rhabdomyolysis.
Coadministration
of
HARVONI
with
rosuvastatin
is not
recommended. |
a. This
table is not all
inclusive.
b. ↓ =
decrease, ↑ =
increase
c. These
interactions
have been
studied in
healthy adults
Drugs
without
Clinically
Significant
Interactions
with HARVONI
Based on drug
interaction
studies
conducted with
the components
of HARVONI
(ledipasvir or
sofosbuvir) or
HARVONI, no
clinically
significant drug
interactions
have been either
observed or are
expected when
HARVONI is used
with the
following drugs
individually:
abacavir,
atazanavir/ritonavir,
cyclosporine,
darunavir/ritonavir,
efavirenz,
emtricitabine,
lamivudine,
methadone, oral
contraceptives,
pravastatin,
raltegravir,
rilpivirine,
tacrolimus,
tenofovir
disoproxil
fumarate, or
verapamil. See
Table above for
use of HARVONI
with certain HIV
antiretroviral
regimens.
Clinical Studies
Treatment-Naïve
Adults without
Cirrhosis -
ION-3 (Study
0108)
ION-3 was a
randomized,
open-label trial
in
treatment-naïve
non-cirrhotic
subjects with
genotype 1 CHC.
Subjects were
randomized in a
1:1:1 ratio to
one of the
following three
treatment groups
and stratified
by HCV genotype
(1a vs 1b):
HARVONI for 8
weeks, HARVONI
for 12 weeks, or
HARVONI +
ribavirin for 8
weeks.
Demographics
and baseline
characteristics
were balanced
across the
treatment
groups. Of the
647 treated
subjects, the
median age was
55 years (range:
20 to 75); 58%
of the subjects
were male; 78%
were White; 19%
were Black; 6%
were Hispanic or
Latino; mean
body mass index
was 28 kg/m2
(range: 18 to 56
kg/m2); 81% had
baseline HCV RNA
levels greater
than or equal to
800,000 IU/mL;
80% had genotype
1a HCV
infection; 73%
had non-C/C
IL28B alleles
(CT or TT).
Table 6
presents the
response rates
for the HARVONI
treatment groups
in the ION-3
trial after 8
and 12 weeks of
HARVONI
treatment.
Ribavirin was
not shown to
increase the
response rates
observed with
HARVONI.
Therefore, the
HARVONI +
ribavirin arm is
not presented in
Table 6.
Table
6 Study ION-3:
Response Rates
after 8 and 12
Weeks of
Treatment in
Treatment-Naïve
Non-Cirrhotic
Subjects with
Genotype 1 CHC
|
HARVONI
8 Weeks
(N=215) |
HARVONI
12 Weeks
(N=216) |
SVR |
94%
(202/215) |
96%
(208/216) |
Outcome
for
Subjects
without
SVR |
On-Treatment
Virologic
Failure |
0/215 |
0/216 |
Relapsea |
5%
(11/215) |
1%
(3/216) |
Otherb |
1%
(2/215) |
2%
(5/216) |
SVR by
Genotypec |
Genotype
1a |
93%
(159/171) |
96%
(165/172) |
Genotype
1b |
98%
(42/43) |
98%
(43/44) |
a. The
denominator for
relapse is the
number of
subjects with
HCV RNA <LLOQ at
their last
on-treatment
assessment.
b. Other
includes
subjects who did
not achieve SVR
and did not meet
virologic
failure criteria
(e.g., lost to
follow-up).
c. One subject
without a
confirmed
subtype for
genotype 1
infection was
excluded from
this subgroup
analysis.
The treatment
difference
between the
8-week treatment
of HARVONI and
12-week
treatment of
HARVONI was
–2.3% (97.5%
confidence
interval –7.2%
to 2.5%). Among
subjects with a
baseline HCV RNA
<6 million
IU/mL, the SVR
was 97%
(119/123) with
8-week treatment
of HARVONI and
96% (126/131)
with 12-week
treatment of
HARVONI.
Relapse rates
by baseline
viral load are
presented in
Table 7.
Table
7 Study ION-3:
Relapse Rates by
Baseline Viral
Load after 8 and
12 Weeks of
Treatment in
Treatment-Naïve
Non-Cirrhotic
Subjects with
Genotype 1 CHC
|
HARVONI
8 Weeks
(N=215) |
HARVONI
12 Weeks
(N=216) |
Number
of
Responders
at End
of
Treatment |
215 |
216 |
Baseline
HCV RNAa |
HCV RNA
<6
million
IU/mL |
2%
(2/123) |
2%
(2/131) |
HCV RNA
≥6
million
IU/mL |
10%
(9/92) |
1%
(1/85) |
a. HCV RNA
values were
determined using
the Roche TaqMan
Assay; a
subject's HCV
RNA may vary
from visit to
visit.
Treatment-Naïve
Adults with or
without
Cirrhosis -
ION-1 (Study
0102)
ION-1 was a
randomized,
open-label trial
that evaluated
12 and 24 weeks
of treatment
with HARVONI
with or without
ribavirin in 865
treatment-naïve
subjects with
genotype 1 CHC
including those
with cirrhosis.
Subjects were
randomized in a
1:1:1:1 ratio to
receive HARVONI
for 12 weeks,
HARVONI +
ribavirin for 12
weeks, HARVONI
for 24 weeks, or
HARVONI +
ribavirin for 24
weeks.
Randomization
was stratified
by the presence
or absence of
cirrhosis and
HCV genotype (1a
vs 1b). The
interim primary
endpoint
analysis for SVR
included all
subjects
enrolled in the
12-week
treatment groups
(N=431). SVR
rates for all
subjects
enrolled in the
24-week
treatment groups
(N=434) were not
available at the
time of interim
analysis.
Demographics
and baseline
characteristics
were balanced
across the
treatment
groups. Of the
865 treated
subjects, the
median age was
54 years (range:
18 to 80); 59%
of the subjects
were male; 85%
were White; 12%
were Black; 12%
were Hispanic or
Latino; mean
body mass index
was 27 kg/m2
(range: 18 to 48
kg/m2); 79% had
baseline HCV RNA
levels greater
than or equal to
800,000 IU/mL;
67% had genotype
1a HCV
infection; 70%
had non-C/C
IL28B alleles
(CT or TT); and
16% had
cirrhosis.
Table 8 presents
the response
rates for the
treatment group
of HARVONI for
12 weeks in the
ION-1 trial.
Ribavirin was
not shown to
increase
response rates
observed with
HARVONI.
Therefore, the
HARVONI +
ribavirin arm is
not presented in
Table 8.
Table
8 Study ION-1:
Response Rates
after 12 Weeks
of Treatment in
Treatment-Naïve
Subjects with
Genotype 1 CHC
with and without
Cirrhosis
|
HARVONI
12 Weeks
(N=214) |
SVRa |
99%
(210/213) |
Outcome
for
Subjects
without
SVR |
On-Treatment
Virologic
Failurea |
0/213 |
Relapsea,b |
<1%
(1/212) |
Othera,c |
1%
(2/213) |
a.
Excluding one
subject with
genotype 4
infection.
b. The
denominator for
relapse is the
number of
subjects with
HCV RNA <LLOQ at
their last
on-treatment
assessment.
c. Other
includes
subjects who did
not achieve SVR
and did not meet
virologic
failure criteria
(e.g., lost to
follow-up).
Response
rates for
selected
subgroups are
presented in
Table 9.
Table
9 Study ION-1:
SVR Rates for
Selected
Subgroups after
12 Weeks of
Treatment in
Treatment-Naïve
Subjects with
Genotype 1 CHC
with and without
Cirrhosis
|
HARVONI
12 Weeks
(N=214) |
Genotypea |
Genotype
1a |
98%
(142/145) |
Genotype
1b |
100%
(67/67) |
Cirrhosisb |
No |
99%
(176/177) |
Yes |
94%
(32/34) |
a. One
subject without
a confirmed
subtype for
genotype 1
infection and
one subject with
genotype 4
infection were
excluded from
this subgroup
analysis.
b. Subjects
with missing
cirrhosis status
were excluded
from this
subgroup
analysis.
14.3
Clinical Trials
in Subjects Who
Failed Prior
Therapy
Previously-Treated
Adults with or
without
Cirrhosis -
ION-2 (Study
0109)
ION-2 was a
randomized,
open-label trial
that evaluated
12 and 24 weeks
of treatment
with HARVONI
with or without
ribavirin in
genotype 1
HCV-infected
subjects with or
without
cirrhosis who
failed prior
therapy with an
interferon-based
regimen,
including
regimens
containing an
HCV protease
inhibitor.
Subjects were
randomized in a
1:1:1:1 ratio to
receive HARVONI
for 12 weeks,
HARVONI +
ribavirin for 12
weeks, HARVONI
for 24 weeks, or
HARVONI +
ribavirin for 24
weeks.
Randomization
was stratified
by the presence
or absence of
cirrhosis, HCV
genotype (1a vs
1b) and response
to prior HCV
therapy
(relapse/breakthrough
vs nonresponse).
Demographics
and baseline
characteristics
were balanced
across the
treatment
groups. Of the
440 treated
subjects, the
median age was
57 years (range:
24 to 75); 65%
of the subjects
were male; 81%
were White; 18%
were Black; 9%
were Hispanic or
Latino; mean
body mass index
was 28 kg/m2
(range: 19 to 50
kg/m2); 89% had
baseline HCV RNA
levels greater
than or equal to
800,000 IU/mL;
79% had genotype
1a HCV
infection; 88%
had non-C/C
IL28B alleles
(CT or TT); and
20% had
cirrhosis.
Forty‑seven
percent (47%) of
the subjects
failed a prior
therapy of
pegylated
interferon and
ribavirin. Among
these subjects,
49% were
relapse/breakthrough
and 51% were
non-responder.
Fifty-three
percent (53%) of
the subjects
failed a prior
therapy of
pegylated
interferon and
ribavirin with
an HCV protease
inhibitor.
Among these
subjects, 62%
were
relapse/breakthrough
and 38% were
non-responder.
Table 10
presents the
response rates
for the HARVONI
treatment groups
in the ION-2
trial. Ribavirin
was not shown to
increase
response rates
observed with
HARVONI.
Therefore, the
HARVONI +
ribavirin arms
are not
presented in
Table 10.
Table
10 Study ION-2:
Response Rates
after 12 and 24
Weeks of
Treatment
in
Subjects with
Genotype 1 CHC
with or without
Cirrhosis who
Failed Prior
Therapy
|
HARVONI
12 Weeks
(N=109) |
HARVONI
24 Weeks
(N=109) |
SVR |
94%
(102/109) |
99%
(108/109) |
Outcome
for
Subjects
without
SVR |
On-Treatment
Virologic
Failure |
0/109 |
0/109 |
Relapsea |
6%
(7/108) |
0/109 |
Otherb |
0/109 |
1%
(1/109) |
a. The
denominator for
relapse is the
number of
subjects with
HCV RNA <LLOQ at
their last
on-treatment
assessment.
b. Other
includes
subjects who did
not achieve SVR
and did not meet
virologic
failure criteria
(e.g., lost to
follow-up).
Among the
subjects with
available SVR12
and SVR24 data
(206/218), all
subjects who
achieved SVR12
in the ION-2
study also
achieved SVR24.
Response
rates and
relapse rates
for selected
subgroups are
presented in
Tables 11 and
12.
Table
11 Study ION-2:
SVR Rates for
Selected
Subgroups after
12 and 24 Weeks
of Treatment
in
Subjects with
Genotype 1 CHC
who Failed Prior
Therapy
|
HARVONI
12 Weeks
(N=109) |
HARVONI
24 Weeks
(N=109) |
Genotype |
Genotype
1a |
95%
(82/86) |
99%
(84/85) |
Genotype
1b |
87%
(20/23) |
100%
(24/24) |
Cirrhosisa |
No |
95%
(83/87) |
99%
(85/86) |
Yes |
86%
(19/22) |
100%
(22/22) |
Prior
HCV
Therapy |
Peg-IFN
+ RBV |
93%
(40/43) |
100%
(58/58) |
HCV
protease
inhibitor
+
Peg-IFN
+ RBV |
94%
(62/66) |
98%
(49/50) |
Response
to Prior
HCV
Therapy |
Relapse/Breakthrough |
95%
(57/60) |
100%
(60/60) |
Nonresponder |
92%
(45/49) |
98%
(48/49) |
a. Subjects
with missing
cirrhosis status
were excluded
from this
subgroup
analysis.
Table
12 Study
ION-2: Relapse
Rates for
Selected
Subgroups after
12 and 24 Weeks
of Treatment in
Subjects with
Genotype 1 CHC
who Failed Prior
Therapy
|
HARVONI
12 Weeks
(N=109) |
HARVONI
24 Weeks
(N=109) |
Number
of
Responders
at End
of
Treatment |
108 |
109 |
Cirrhosisa |
No |
5%
(4/86)b |
0%
(0/86) |
Yes |
14%
(3/22) |
0%
(0/22) |
Presence
of
Baseline
NS5A
Resistance-Associated
Polymorphismsc |
No |
2%
(2/85) |
0%
(0/90) |
Yes |
22%
(5/23) |
0%
(0/19) |
IL28B
Status |
C/C |
0%
(0/10) |
0%
(0/16) |
Non-C/C |
7%
(7/98) |
0%
(0/93) |
a. Subjects
with missing
cirrhosis status
were excluded
from this
subgroup
analysis.
b. These 4
non-cirrhotic
relapsers all
had baseline
NS5A
resistance-associated
polymorphisms.
c. NS5A
resistance-associated
polymorphisms
include any
change at NS5A
positions 24,
28, 30, 31, 58,
92, or 93.
HARVONI is a
product of
Gilead Sciences,
Inc..
The complete
product label
will be
available soon
at
DailyMed or
at
Drugs@FDA.
Also see:
FDA Press
Release
Richard Klein
Office of Health
and Constituent
Affairs
Food and Drug
Administration
Kimberly
Struble
Division of
Antiviral
Products
Food and Drug
Administration
Steve Morin
Office of Health
and Constituent
Affairs
Food and Drug
Administration