Post-Conference
Highlights:
This year's AASLD conference provided a wealth of
information about the new direct-acting antiviral agents (DAAs) to treat
hepatitis C. I have summarized below
some of the more interesting presentations and posters. There is still much
information that I am reviewing and I will update the report via our website as
needed, and I will include more information and analyses of the most important
or interesting data presented at AASLD in the December 2010 HCV Advocate newsletter.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Post-conference
highlights: Telaprevir
– see HCSP
Fact Sheet.
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.