Below is a press release from Pharmasset describing the new
Initiates Phase 1b Multiple Ascending Dose
Clinical Trial of PSI-938 in Patients with Chronic Hepatitis
NJ -- July 28, 2010 -- Pharmasset, Inc. (NASDAQ:VRUS) announced
today that safety and pharmacokinetic data from the PSI-352938
("PSI-938") single ascending dose study support progression
to a multiple ascending dose trial with PSI-938, which has initiated
dosing. PSI-938 is a guanine nucleotide analog polymerase inhibitor
for the treatment of chronic hepatitis C virus (HCV) infection.
This study is designed to assess the safety, tolerability and
antiviral activity of PSI-938 monotherapy administered over
7 days in HCV-infected individuals.
"PSI-938 is the third differentiated nucleoside analog
that Pharmasset has advanced into clinical development for HCV,"
stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical
Officer. "As with RG7128 and PSI-7977, PSI-938 demonstrates
a high barrier to resistance in vitro; but unlike the cytidine
and uridine analogs, PSI-938 retains equivalent potency against
the S282T mutant. As the HCV field moves toward IFN-sparing,
all-oral DAA [direct-acting antiviral] combinations, we continue
to believe nucleosides could become the backbone of care given
these differentiating attributes and have the potential to be
combined with all DAA classes."
PSI-938 Phase 1 Program Overview
The Phase 1 program is investigating the safety, tolerability
and pharmacokinetics of PSI-938 in healthy subjects following
escalating single doses (Phase 1a), and in patients chronically
infected with HCV genotype 1 following repeat dosing for 7 days
(Phase 1b). The Phase 1b study will additionally investigate
hepatitis C viral dynamics and monitor for the development of
Subjects in the Phase 1a single ascending dose study received
single doses of PSI-938 ranging from 100 mg to 800 mg or a matching
placebo. Preliminary data from the phase 1a single ascending
dose study includes:
serious adverse events or discontinuations;
dose-related adverse events or dose-limiting toxicity;
grade III / IV lab abnormalities;
clinically significant changes in vital signs or ECGs; and
which supports QD dosing.
Phase 1b multiple ascending dose trial has now been initiated
in treatment-naive patients with chronic HCV genotype 1 infection.
Subjects will be enrolled at multiple centers in the US and
randomized to PSI-938 or placebo. Based upon the results from
the first time in human study, the first dose of PSI-938 to
be tested will be 100 mg administered once daily. The primary
objectives of this study are to assess the safety, tolerability,
pharmacokinetics and viral dynamics of PSI-938 after repeat
dosing over 7 days.
Results from both studies are expected in the third quarter
Purine and Pyrimidine Analogs
purine nucleoside/tide analogs share many of the benefits of
pyrimidine nucleoside/tide analogs, such as RG7128 and PSI-7977,
in that they have demonstrated in vitro activity across multiple
HCV genotypes, have a higher barrier to resistance than other
classes of HCV small molecules in development, and, in spite
of the prodrug technology, have no CYP 3A4 liability and thus
a lower risk of drug interactions when combined with other direct
acting antivirals targeting HCV. In addition, Pharmasset's purine
analogs retain equivalent potency against wild type HCV and
virus with the S282T mutation associated with in vitro resistance
in other nucleoside/tide analogs in development. Furthermore,
the purines are metabolized to the active triphosphate form
through a different phosphorylation pathway than the pyrimidine
analogs, thus decreasing the risk of competition between the
two analogs for conversion to the active triphosphate. Given
these characteristics, Pharmasset's purine and pyrimidine analogs
have the potential to be combined as part of a future treatment
regimen, which will be the focus of upcoming trials.
is a clinical-stage pharmaceutical company committed to discovering,
developing, and commercializing novel drugs to treat viral infections.
Pharmasset's primary focus is on the development of oral therapeutics
for the treatment of hepatitis C virus (HCV) and, secondarily,
on the development of Racivir for the treatment of human immunodeficiency
virus (HIV). Our research and development efforts focus on nucleoside/tide
analogs, a class of compounds which act as alternative substrates
for the viral polymerase, thus inhibiting viral replication.
We currently have four clinical-stage product candidates. RG7128,
a cytosine analog for chronic HCV infection, is in two Phase
2b clinical studies in combination with Pegasys plus Copegus
and is also in the INFORM
studies, the first series of studies designed to assess
the potential of combinations of small molecules without Pegasys
and Copegus to treat chronic HCV. These clinical studies are
being conducted through a strategic collaboration with Roche.
Our other clinical stage HCV candidates include PSI-7977, an
unpartnered uracil nucleotide analog that has recently completed
a Phase 2a study, and PSI-938, an unpartnered guanine nucleotide
analog in Phase 1. We also have in our pipeline an additional
purine nucleotide analog, PSI-661, in advanced preclinical development.
Racivir, for the treatment of HIV, has completed a Phase 2 clinical
Inc. Pharmasset Initiates Phase 1b Multiple Ascending Dose Clinical
Trial of PSI-938 in Patients with Chronic Hepatitis C. Press
release. July 28, 2010.