Jan. 9, 2012, 6:00 a.m. EST
SAN FRANCISCO, Jan 09, 2012 (BUSINESS WIRE) -- Presidio Pharmaceuticals, Inc.
announced today the successful completion of a Phase 1a dose-ranging assessment
of PPI-668, a potent, pan-genotypic second-generation hepatitis C virus (HCV)
NS5A inhibitor, in healthy volunteers and subsequent advancement to a Phase 1b
assessment of the dose-related efficacy in hepatitis C patients.
The Phase 1a dose-ranging assessment of PPI-668 was conducted with 32 healthy
volunteers in New Zealand. The trial was a randomized, double-blind,
placebo-controlled assessment of the safety and pharmacokinetics of three oral
doses of PPI-668, initially assessed as single doses and subsequently as a
multi-day regimen, in which the highest PPI-668 dose was given once daily for
five successive days. The trial results indicated that all dose regimens of
PPI-668 were well-tolerated. There were no serious or severe clinical adverse
events, no patterns of treatment-related adverse events or laboratory
abnormalities, and all subjects completed the trial successfully.
Pharmacokinetic (PK) analyses of subjects' plasma samples in the Phase 1a
trial indicated that substantial blood levels of PPI-668 were rapidly and
consistently achieved and dose proportional. PPI-668 plasma concentrations were
orders of magnitude above those shown to inhibit HCV replication in vitro and
were maintained at predicted effective concentrations for more than 24 hours.
These PK results support once-daily dosing for PPI-668 in future studies. Also
important was the observation that in the 5-day multi-dose regimen, steady-state
PK was achieved rapidly (by Day 2), with no evidence of subsequent accumulation
or changes in the clearance profile of PPI-668.
"These first clinical data for PPI-668 indicate excellent tolerance in
healthy subjects for up to five days," said Nathaniel A. Brown, M.D., Presidio's
Chief Medical Officer. "Equally important, the pharmacokinetic profile of
PPI-668 is very encouraging, suggesting that effective plasma concentrations can
be obtained with relatively low, once-daily doses of PPI-668 - which will
facilitate co-formulation of PPI-668 with other HCV antivirals in future
combination therapies for hepatitis C."
Patient screening for the Phase 1b evaluation of PPI-668 in hepatitis C
patients has begun in New Zealand and the United States and will soon include
Australia. Dosing of the first cohort of hepatitis C patients will begin this
week. Presidio expects to have results regarding the antiviral efficacy of
PPI-668 in HCV patients in the second quarter of 2012.
In a second HCV research program focused on inhibitors of the HCV NS5B
polymerase, Presidio has discovered a lead chemical series of non-nucleosidic
NS5B inhibitors with potent activity against all major HCV genotypes.
Preclinical profiling is ongoing with a goal of nominating a candidate for
clinical development in the coming months.
With its novel NS5A and NS5B inhibitors, Presidio's objective is to provide
two complementary HCV antivirals that will be appropriate for broad use in
optimized future combination therapies for patients with HCV infection. Presidio
anticipates that such therapies will have a convenient oral dosing regimen (once
or twice daily), will exhibit rapid pan-genotypic efficacy and will be
well-tolerated.
ABOUT HEPATITIS C AND NS5A INHIBITORS
Chronic hepatitis C is a persistent, potentially progressive inflammatory
liver disease caused by chronic infection with the hepatitis C virus (HCV).
Worldwide there are an estimated 130 to 170 million persons with chronic HCV
infection. There are 7 major genotypes (strains) of HCV, which have differing
geographic distributions. Globally, about 40-60% of patients are infected with
HCV genotype-1, with the remaining patients infected with HCV genotypes 2
through 7.
Patients with advanced hepatitis C can develop potentially fatal liver
failure or liver cancer, and hepatitis C is estimated to account for over
350,000 deaths per year worldwide (WHO estimate). The current standard-of-care
treatment for hepatitis C in the United States, for patients with HCV genotype-1
infection, is combined administration of pegylated-interferon, ribavirin, and
first-generation HCV protease inhibitors. This multi-drug treatment is
characterized by incomplete efficacy for HCV genotype-1 patients, variations in
efficacy according to patients' underlying human genetic factors, no established
efficacy for patients infected with other HCV genotypes, substantial tolerance
issues, and dosing inconveniences. Thus, there is a continuing need for more
consistently effective and better tolerated HCV inhibitors that can be orally
administered in future combination therapies for hepatitis C patients worldwide,
regardless of HCV genotype, patient genetic factors, or disease stage.
Inhibitors of the HCV NS5A protein represent an exciting, relatively new
class of HCV inhibitors that, when optimized, exhibit potent activity across all
HCV genotypes, with a mechanism that is distinct from other classes of HCV
antivirals, which commonly target the HCV protease or polymerase. PPI-668 is a
novel, optimized, second-generation HCV NS5A inhibitor, which exhibits highly
potent and selective activity against all HCV genotypes in replicon assays, with
favorable toxicology and pharmacology profiles in preclinical assessments.
ABOUT PRESIDIO
Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage
specialty pharmaceutical company dedicated to the discovery and development of
small-molecule antiviral therapeutics for hepatitis C virus (HCV). For more
information, please visit our website at: www.presidiopharma.com.
SOURCE: Presidio Pharmaceuticals, Inc.
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