Direct-Acting Antiviral Agents (DAA’s)
ABT-450
Pre-conference
summary: HCV
Protease Inhibitor—Phase I studies.
Studies are underway to assess multiple doses for a 3-day period. These studies will be followed by ABT-450 in combination
with pegylated interferon plus ribavirin for 12 weeks followed by an additional
36 weeks of pegylated interferon plus ribavirin. All patients are HCV genotype 1 treatment
naïve.
·
1855. Initial antiviral activity of the HCV NS3 protease inhibitor ABT-450
when given with low dose ritonavir as 3-day monotherapy: Preliminary results of
study M11-602 in genotype-1 (GT1) HCV-infected treatment-naïve subjects.
(Updated November
4, 2010)
·
LB-10. 4-week virologic response and safety of
ABT-450 given with low-dose ritonavir (ABT-450/r) in combination with pegylated
interferon alpha-2a and ribavirin (SOC) after 3-day monotherapy in genotype 1
(GT1) HCV-infected treatment-naïve subjects (Updated November 4,
2010)
Post-conference
highlights: ABT-450
is a protease inhibitor that is being tested in HCV treatment-naïve genotype 1
subjects as a combination therapy that includes ritonavir (boosting agent) and
pegylated interferon plus ribavirin.
For three days the trial participants were given ABT-450 (boosted with
ritonavir) at doses ranging from 50 to 200 once a day followed by quadruple
therapy of ABT-450 (with ritonavir) plus pegylated interferon and ribavirin for
12 weeks followed by 36 weeks of pegylated interferon. At the end of week 4, 21 of 23 (91.3%) were
HCV RNA negative (<25IU/mL) compared to 1 of 8 (12.5%) of those who received
the placebo. The medications were safe
and well-tolerated.
ACH-2684
Pre-conference summary:
HCV
Protease Inhibitor—no data available
·
1859. ACH-2684: HCV NS3 Protease Inhibitor with Potent Activity against
Multiple Genotypes and Known Resistant Variants. (Updated November
8, 2010)
Post-conference
highlights: ACH-2684
was found to be active against genotypes 1 to 6 (pan genotypic) and was found
to work with multiple protease inhibitors.
The development of the drug will move forward.
ACH-2928
Pre-conference
summary: HCV
NS5A Inhibitor—no data available
·
1880. In Vitro Combination Studies of ACH-1625 (HCV NS3 Protease Inhibitor)
and ACH-2928 (HCV NS5A inhibitor) in Presence and Absence of Ribavirin. (Updated
November 8, 2010)
Post-conference
highlights: It was
found that when ACH-1655 (protease
inhibitor) and ACH2928 (NS5A
inhibitor) were combined there was a synergistic affect that was enhanced when
combined with ribavirin.
ANA598
Pre-conference
summary: HCV
Polymerase Inhibitor—Phase II studies.
In a small study of people who received triple therapy of ANA598,
pegylated interferon and ribavirin 75% of patients taking the twice-daily dose
of 400 mg were HCV RNA after 12 weeks.
·
31. Safety and Antiviral
Activity of ANA598 in Combination with Pegylated Interferon α2A Plus
Ribavirin in Treatment-Naïve Genotype-1 Chronic HCV Patients (Updated November 5, 2010)
Post-conference
highlights: There is an
ongoing study of ANA598 (in multiple
doses) combined with pegylated interferon plus ribavirin. 29 HCV genotype 1 treatment-naïve patients
received the triple therapy for 12 weeks and were randomized (depending of
treatment response) to an additional 12 or 36 weeks. The SVR 12 results in the patients who
completed 24 weeks of treatment was 73% (in eight
patients). The most common side effect
was rash and it was observed in 59% of the patients who received the 400 mg
dose.
BI 201335
Pre-conference
summary: HCV
Protease Inhibitor—Phase II studies.
Interim 12 week results of 280 HCV genotype 1 prior non-responders who will
be treated for a total of 24 weeks with BI 201335 in combination with pegylated
interferon plus ribavirin found that 54 to 59% were HCV RNA negative at week
12.
BI 207127
Pre-conference
summary: HCV Polymerase Inhibitor—Phase
II studies. In a 5 day monotherapy study
of HCV Genotype 1 patients a median 3.8 log10 viral load
decrease was reported.
·
LB-7. Strong antiviral activity and safety of IFN-sparing treatment with
the protease inhibitor BI 201335, the HCV polymerase inhibitor BI 207127 and
ribavirin in patients with chronic hepatitis C (Updated November 1, 2010)
·
1862. Genotypic and
phenotypic analysis of the NS5B polymerase region from viral isolates of HCV
chronically infected patients treated with BI 207127 for 5-days monotherapy
(Updated November 8, 2010)
Post-conference
highlights:
In this study (without interferon) the triple regime of BI 201335 (protease inhibitor) plus BI 207127 (polymerase inhibitor) and
ribavirin to treat HCV genotype 1 treatment-naïve patients was found to provide
strong antiviral activity—additional studies with longer durations are planned
to evaluate sustained virological response rates.
BMS-65032 (HCV Protease
Inhibitor); BMS-650032 (Protease Inhibitor); BMS-790052 (NS5a inhibitor);
BMS-791325 (Polymerase Inhibitor); BMS-824393 (NS5A Inhibitor)
Pre-conference
summary: BMS
has multiple drugs in Phase I and Phase II studies combined with pegylated
interferon and ribavirin and in combination studies of their DDA’s without
pegylated interferon or ribavirin.
·
LB-8. Combination therapy with BMS-790052 and BMS-650032 alone or with
pegIFN/RBV results in undetectable HCV RNA through 12 weeks of therapy in HCV
genotype 1 null responders (Updated November 4, 2010)
·
827. Co-administration of BMS-790052 and BMS-650032 does not result in a
Clinically Meaningful Pharmacokinetic Interaction in Healthy Subjects.
(Updated October
31, 2010)
·
1858. BMS-824393 is a
Potent Hepatitis C Virus NS5A Inhibitor with Substantial Antiviral Activity
when given as Monotherapy in Subjects with Chronic G1 HCV Infection (Updated November 8, 2010)
Post-conference
highlights: In an important study the combination of
BMS-650032 (protease inhibitor) and BMS-790052 was given to genotype 1
null-responders to a prior course of therapy.
The interim results at 12 weeks (total study duration is 24 weeks)
produced early antiviral activity, but 6 out of the 11 people treated had viral
breakthrough indicating that pegylated interferon and/or ribavirin will be
needed to completely suppress the virus at least in this study. When the combination was combined with
pegylated interferon and ribavirin 9 out of 10 patients became HCV RNA
undetectable by week 12.
Boceprevir
Pre-conference
summary: HCV Protease Inhibitor—Top line results from 2 Phase
III studies of boceprevir, pegylated interferon plus ribavirin used to treat
HCV genotype 1 patients reported that in treatment naïve patients (never been
treated) 63 to 66% of patients achieved an SVR; People who had been treated
with a prior course of pegylated interferon plus ribavirin, but did not achieve
an SVR and who were treated with the triple combination achieved 59-66% SVR
rates. For more
information click here
to view the boceprevir HCSP Fact Sheet.
·
LB-15. Response-Guided Therapy (RGT) with Boceprevir (BOC) + Peginterferon alfa-2b/Ribavirin
(P/R) for Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype (G) 1
Was Similar to a 48-Wk Fixed-Duration Regimen with BOC + P/R in SPRINT-2.
(Updated November
9, 2010)
·
216.
HCV RESPOND-2 Final Results: High Sustained Virologic Response Among Genotype 1
Previous Non-Responders and Relapsers to Peginterferon/Ribavirin when
Re-Treated with Boceprevir Plus PEGINTRON (Peginterferon alfa-2b)/Ribavirin
(Updated November 9, 2010)
Danoprevir (RG7227)
Pre-conference
summary: HCV
Protease Inhibitor—Phase II studies. Currently in combination with pegylated interferon plus ribavirin
and ritonavir (boosting agent). A
small study found that after 15 days of treatment that 50% to 100% of patients
were HCV RNA negative.
·
802.
Low rate of viral load rebound observed among treatment-naive genotype 1
patients with chronic hepatitis C treated with danoprevir (RG7227) plus PegIFN
α-2a (40KD) (PEGASYS®) plus ribavirin: interim analysis. (Updated November 8, 2010)
·
32. Phase II randomized,
partially-blind, parallel-group study of oral danoprevir (RG7227) with
PegIFNα-2a (PEGASYS®) plus ribavirin in treatment-naive genotype 1
patients with CHC: Results of planned Week 12 interim analysis of the ATLAS
study. (Updated November 5,
2010)
Post-conference
highlights: Interim
results using various doses of danoprevir
combined with pegylated interferon plus ribavirin found that 88 to 92% were
HCV RNA negative by week 12 compared to 43% in the placebo group. More studies are planned including a study
using ritonavir as a boosting agent.
Filibuvir
Pre-conference summary: HCV Polymerase Inhibitor—Phase II
studies. Study results from 35 patients
who were treated with filibuvir, pegylated interferon and ribavirin found that
75% were HCV RNA negative after 4 weeks of treatment.
GS-9256/GS-9190
Pre-conference
summary: HCV Protease
Inhibitor/Polymerase Inhibitor—Phase II studies. Studies include GS_9356 with and without
ribavirin and the combination of GS-9256 and GS-9190 with and without ribavirin
(both regimes contain pegylated interferon)
·
LB-1. Dual, Triple, and Quadruple Combination Treatment with a Protease
Inhibitor (GS-9256) and a Polymerase Inhibitor (tegobuvir-GS-9190) alone and in
Combination with Ribavirin (RBV) or PegIFN/RBV for up to 28 days in Treatment
Naïve, Genotype 1 HCV Subjects (Updated November 8, 2010)
·
833. Antiviral Response and Resistance Analysis of Treatment-Naïve HCV
Infected Subjects Receiving Single and Multiple Doses of GS-9190.
(Updated October
31, 2010)
Post-conference
highlights: The
combination of GS-9256 (HCV protease
inhibitor) plus tegobuvir (GS-9190 –
polymerase inhibitor) when combined with pegylated interferon plus ribavirin
produced the best results. The quadruple
group was given for 4 weeks followed by 44 weeks of pegylated interferon plus
ribavirin. 14 out of 14 patients were
HCV RNA negative by day 28. There is an
ongoing 4 month study of the quadruple therapy.
IDX184
Pre-conference
summary: HCV
Polymerase Inhibitor—Phase II studies –currently the studies are on hold due to
safety concerns.
IDX320
Pre-conference
summary: HCV
Polymerase Inhibitor—Phase II studies—currently the studies are on hold due to
safety concerns.
IDX375
Pre-conference
summary: HCV
Polymerase Inhibitor—Phase 1 studies. IDX375 given in
5 doses once daily or twice daily was found the drug to be safe and
well-tolerated.
·
1891. Phase I Study in
Healthy Volunteers and Patients with IDX375, a Novel Non-Nucleoside HCV
Polymerase Inhibitor (Updated November 8, 2010)
IMO-2125
INX-189
Pre-conference
summary: HCV
Polymerase Inhibitor—Phase I
studies. INX-189 was found to be safe
and well-tolerated and had the potential for a once-a-day dose.
MK-3281
Pre-conference
summary: HCV
Polymerase Inhibitor—phase I study
results from a small group of 22 HCV
treatment-naive and treatment-experienced patients. In the genotype 1b
group there was found to be a 3.75 log10
decrease in HCV RNA.
MK-5172
Pre-conference
summary: HCV
Protease Inhibitor—no data available
MK-7009 (Vaniprevir)
Pre-conference
summary: NS3/4a
Protease Inhibitor —no data available
·
82. Sustained Viral Response (SVR)
Rates in Genotype 1 Treatment-naïve Patients with Chronic Hepatitis C (CHC)
Infection Treated with Vaniprevir (MK-7009), a NS3/4a Protease Inhibitor, in
Combination with Pegylated Interferon Alfa-2a and Ribavirin for 28 Days (Updated November 2, 2010)
Post-conference
highlights: Vaniprevir—A
study of 45 HCV genotype 1 treatment-naïve patients who were administered 1 of
5 regimens—placebo, 300 mg BID (twice a day), 600 mg BID, 600 mg QD (once a
day) or 800QD in combination with pegylated interferon plus ribavirin for 4
weeks followed by an additional 44 weeks of pegylated interferon resulted in
SVR rates of 78 to 84% compared to 63% in the placebo (only pegylated
interferon and ribavirin). Note: the high SVR rate in the placebo group is
likely due to the small patient population in this group.
PPI-461
Pre-conference
summary: NS5A
Inhibitor —no data available
·
LB-12. Safety and
Pharmacokinetics of PPI-461, a Potent New Hepatitis C Virus (HCV) NS5A
Inhibitor with Pan-Genotype Activity (Updated November 8, 2010)
Post-conference
highlights: A
total of forty healthy volunteers were given PPI-461, an NS5A inhibitor for up to 5 days and it was found that
the plasma levels of PPI-461 were reached within 1-4 hours. No serious adverse events were noted. PPI-461 is pan-genotypic (activity against
all genotypes). This study warranted
exploring a once-a-day dosing in HCV patients.
PSI-352938
Pre-conference
summary: HCV
Polymerase Inhibitor—no data available
·
1890. Pharmacokinetics,
Safety, and Tolerability of PSI-352938, a Novel Nucleotide Polymerase Inhibitor
for HCV, Following Single Ascending Oral Doses in Healthy Subjects. (Updated November 8, 2010)
Post-conference
highlights: PSI-352938,
a protease inhibitor, was tested in healthy volunteers at doses ranging from 25
to 1600 mg and was found to be generally safe and well-tolerated. Based on this
study a mono-therapy study is being conducted in genotype 1 patients.
PSI-7977
Pre-conference
summary: HCV
Polymerase Inhibitor—in Phase IIa studies. PSI-7977 used in combination with pegylated
interferon plus ribavirin for the treatment of people with HCV genotype 1
treatment naïve (never been treated) patients.
Interim results found that 88 to 94% of patients were HCV RNA negative
after 28 days of treatment.
·
806. High Rapid Virologic Response (RVR) with PSI-7977 QD plus PEG-IFN/RBV
in a 28-day Phase 2a Trial.
(Updated October
31, 2010)
·
815. IL28B SNP Geographical Distribution and Antiviral Responses in a 28-day
Phase 2a Trial of PSI-7977 Daily Dosing plus PEG-IFN/RBV. (Updated November 8,
2010)
·
1861. Clinical synergy of an Anti-HCV Nucleoside Analog with SOC: Viral
Kinetics of PSI-7977 with SOC (Updated November 8, 2010)
Post-conference
highlights: PSI-7977,
a polymerase inhibitor, dosed once a day (100, 200 and 400 mg) combined with
pegylated interferon plus ribavirin for 28 days produced 4 week RVRs of 88 to
94% compared to 21% in the pegylated interferon plus ribavirin group (without
PSI-7977). AT week 12 the cEVR (complete early virological response) was highest in
the 200 mg QD (94%) and 400 (87%) compared to 64% cEVR
in the pegylated interferon plus ribavirin (placebo) group. Based on these results a 12 week study is
being planned. In addition PSI-7977
appears to work against different genotypes.
RG7128
Pre-conference
summary: HCV
Polymerase Inhibitor—Phase II studies.
The studies will enroll 400 HCV genotype 1 or 4 patients in combination
with Pegasys/ribavirin. Interim results
found that more than 80% of patients were HCV RNA undetectable after 12 weeks
of treatment with the triple combination therapy.
·
81. High rates of early viral response, promising safety profile and lack
of resistance-related breakthrough in HCV GT 1/4 patients treated with RG7128 plus
PegIFN alfa-2a (40KD)/RBV: Planned Week 12 interim analysis from the PROPEL
study. (Updated November 5, 2010)
Post-conference
highlights: RG7128
(500 or 1000 mg - BID) combined with pegylated interferon plus ribavirin was
given in different doses and time lines based on response and it was found that
RG7128 was safe and well-tolerated in HCV genotype 1 and 4 treatment-naïve
patients with and without cirrhosis. The
group that received the 8 or the 12 week regime of 1000 mg BID achieved the
highest declines in HCV RNA (viral load) levels. RG7128 appears to have a high barrier to drug
resistance.
SCY-635
Pre-conference
summary: Cyclophilin
Inhibitor —no data available
Telaprevir
Pre-conference
summary: HCV
Protease Inhibitor—Phase III studies. Top line results from 3 clinical trials
of the triple combination of telaprevir, pegylated interferon plus ribavirin in
people with HCV Genotype 1 found that in treatment naïve patients (never been
treated) there was a sustained virological response (SVR) of 69-75% and up to
76% SVR in people who had been treated with pegylated interferon plus ribavirin
but who did achieve an SVR. For more information click here
to view the Telaprevir HCSP Fact Sheet.
·
LB-11. Clinical Virology Results from Telaprevir Phase 3 Study ADVANCE.
·
LB-2. Telaprevir in Combination with Peginterferon Alfa2a and Ribavirin for
24 or 48 weeks in Treatment-Naïve Genotype 1 HCV Patients who Achieved an
Extended Rapid Viral Response: Final Results of Phase 3 ILLUMINATE Study
(Updated November
9, 2010)
·
211. Telaprevir in Combination with Peginterferon and Ribavirin in
Genotype 1 HCV Treatment-Naïve Patients: Final Results of Phase 3 ADVANCE
Study.
(Updated November 9, 2010)
·
227. Long-term Follow-up of Patients with Chronic Hepatitis C Treated with
Telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin: Interim
Analysis of the EXTEND Study. (Updated November 2, 2010)
Post-conference
highlights: Telaprevir
– see HCSP
Fact Sheet.
TMC435
Pre-conference
summary: HCV
Protease Inhibitor—Phase IIa studies. Interim data (SVR12) from a 24-week triple
combination therapy of TMC435, pegylated interferon and ribavirin to treat HCV
genotype 1 treatment naïve patients found that in those patients who completed
the entire 24 treatment duration achieved a 80% to 90%
SVR12.
·
812. Virologic analysis of genotype-1-infected patients treated with
once-daily TMC435 during the Optimal Protease inhibitor Enhancement of Response
to therApy (OPERA)-1 study. (Updated October 31,
2010)
Post-conference
highlights:
Interim results for a study of TMC435
(75 and 150 mg QD) combined with pegylated interferon plus ribavirin given for
up to 24 weeks produced significant viral load reductions. In patients who completed 24 weeks treatment
or stopped treatment for any reason by week 24 the SVR results ranged from 88
to 97% (119 out of 130 patients). So far there is a low rate of viral
breakthrough.