PSI-7977
Trial Adds New Regimens
SUMMARY
The ELECTRON trial, testing the HCV polymerase inhibitor PSI-7977,
has added new arms looking at regimens with shorter duration
or no interferon for people with HCV genotypes 1, 2, and 3. |
Direct-acting
antiviral agents that interfere with various steps of the hepatitis
C virus (HCV) lifecycle will revolutionize treatment. Initially
these drugs will be used with standard therapy consisting of pegylated
interferon alfa (Pegasys or PegIntron) plus ribavirin. While
such regimens have higher cure rates and shorter durations, people
with hepatitis C eagerly await
combinations without interferon and its difficult side effects.
The experimental nucleotide HCV polymerase inhibitor PSI-7977
has demonstrated potent activity in early studies to date, suggesting
that it may be a good candidate for use in interferon-sparing
regimens. This might be especially true for people with easier-to-treat
HCV genotypes 2 or 3. Studies
presented at this year's European Association for the Study
of the Liver (EASL) meeting showed promising results for people
treated with PSI-7977 plus pegylated interferon/ribavirin or an
all-oral combo of PSI-7977 plus PSI-938.
Below
is an edited excerpt from a Pharmasset press release describing
addition of new trial arms to the ongoing ELECTRON study looking
at PSI-7977 regimens with no interferon or shorter-duration interferon.
Pharmasset Announces the Expansion of the
ELECTRON Trial in Chronic Hepatitis C
Princeton,
N.J. -- June 8, 2011 -- Pharmasset, Inc. (Nasdaq: VRUS) announced
today the addition of three treatment cohorts to the ELECTRON
trial of PSI-7977, a nucleotide analog polymerase inhibitor, for
the treatment of chronic hepatitis C (HCV). The rapid and consistent
antiviral effects and high barrier to resistance demonstrated
with PSI-7977 to date provide the rationale for additional exploratory
regimens in this setting. This amendment will add one arm exploring
12 weeks of PSI-7977 monotherapy (without peginterferon and ribavirin)
and two arms of interferon-sparing therapy: one for 8 weeks of
PSI-7977 plus peginterferon and ribavirin (Peg-IFN/RBV) in patients
with HCV genotype 2 (GT2) or 3 (GT3) and one for 12 weeks of PSI-7977
plus Peg-IFN/RBV in patients with HCV genotype 1 (GT1) prior null
responses.
"The combination data reported at EASL demonstrated that
SVRs were achievable with two oral DAAs in the absence of peginterferon
and ribavirin," stated Bill Symonds, PharmD, Pharmasset's
Senior Vice President of Clinical Pharmacology and Translational
Medicine, "We continue to explore the potential for removing
peginterferon and ribavirin from the HCV treatment regimen. Given
the encouraging data we are seeing in ELECTRON, we have decided
to expand the study to investigate PSI-7977 monotherapy, as well
as shorter treatment regimens based on the promising data we reported
at EASL from PROTON."
Pharmasset anticipates reporting results from the first four arms
of the trial (n=40) during the second half of 2011. We have submitted
a number of abstracts to the 2011 American Association for the
Study of Liver Diseases (AASLD) meeting, including data from the
ELECTRON and PROTON trials.
About the Trial
The ELECTRON trial is an exploratory study of PSI-7977 for the
treatment of chronic HCV infection. Part 1 of the trial is evaluating
12-week regimens of PSI-7977 400 mg QD [once-daily] in combination
with ribavirin (RBV) only, and in separate arms with abbreviated
durations of Peg-IFN for 4, 8, or 12 weeks in treatment-naive
patients with HCV GT2 or GT3. The primary endpoint of the trial
is the safety and tolerability of PSI-7977 400 mg QD and RBV for
12 weeks, administered with or without Peg-IFN. On May 11, 2011,
Pharmasset announced the completed enrollment of Part 1 of ELECTRON
in patients with HCV GT 2 or GT 3:
 |
PSI-7977
400 mg with RBV for 12 weeks (no peginterferon); |
|
PSI-7977
400 mg with RBV for 12 weeks; Peg-IFN weeks 1-4 only; |
|
PSI-7977
400 mg with RBV for 12 weeks, Peg-IFN weeks 1-8 only; |
|
PSI-7977
400 mg with Peg-IFN and RBV for 12 weeks. |
In
Part 2 of ELECTRON, Pharmasset will enroll an additional 30 patients
into exploratory regimens of monotherapy and abbreviated durations
of total therapy. Following on the first four Cohorts of ELECTRON
a 5th cohort will be added to explore 7977 400 mg monotherapy
in treatment-naive patients with HCV GT2 or GT3:
|
PSI-7977 400 mg monotherapy for 12 weeks. |
With
the previously reported 100% SVR12 in naive GT2/3 subjects in
PROTON, a 6th and 7th cohort will be added to ELECTRON to explore
shorter treatment durations in both GT2/3 naive subjects and HCV
GT1 subjects who have documented null responses (less than 2 log(10)
IU/mL reduction in HCV RNA after 12 weeks of Peg-IFN/RBV):
|
PSI-7977
400 mg with Peg-IFN/RBV for 8 weeks |
|
PSI-7977
400 mg QD with Peg-IFN/RBV for 12 weeks. |
About
Pharmasset
Pharmasset
is a clinical-stage pharmaceutical company committed to discovering,
developing, and commercializing novel drugs to treat viral infections.
Pharmasset's primary focus is the development of oral therapeutics
for the treatment of hepatitis C virus (HCV) infection. Our research
and development efforts are focused on nucleoside/tide analogs,
a class of compounds which act as alternative substrates for the
viral polymerase, thus inhibiting viral replication.
We currently have three clinical-stage product candidates advancing
in trials in various populations. Our pyrimidine, PSI-7977, an
unpartnered uracil nucleotide analog, is currently under study
in three Phase 2b trials in patients with HCV genotypes 1 through
6, including abbreviated duration interferon and interferon-free
regimens. Our purine, PSI-938, an unpartnered guanosine nucleotide
analog, recently reported safety and efficacy data from 14 days
of monotherapy as well as 14 days in combination with the pyrimidine,
PSI-7977. An SVR-endpoint study of the purine-pyrimidine combination
is anticipated to begin in the third quarter of 2011. Mericitabine
(RG7128) continues in two Phase 2b trials and one interferon-free
trial being conducted through a strategic collaboration with Roche.
6/14/11
Source
Pharmasset, Inc. Pharmasset Announces the Expansion of the ELECTRON
Trial in Chronic Hepatitis C. Press release. June 8, 2011.
