Presidio Pharmaceuticals, Inc. announced today successful completion of
Phase 1b clinical testing of its lead HCV NS5A inhibitor in patients
with HCV genotype-1 infection, with positive efficacy and safety
observations supporting advancement of PPI-668 to Phase 2 combination
cohorts of treatment-naive HCV genotype-1 patients who received oral
doses of PPI-668 of 40, 80, 160 or 240 mg, once daily for three
consecutive days. Within each 10-patient cohort, patients were
randomized 8:2 to PPI-668 or placebo.
serious or severe adverse events, no premature treatment
discontinuations and no apparent pattern of treatment-related clinical
side effects or laboratory abnormalities.
pharmacokinetic (PK) profile that included rapid achievement of high
(micromolar) plasma levels, prolonged maintenance of potentially
effective levels between doses, and achievement of steady-state
pharmacokinetics after the first dose.
The Phase 1b efficacy observations indicated consistently rapid, marked
reductions in patients’ serum viral load (HCV RNA levels), that were
dose-related. Patients’ HCV RNA reductions typically exceeded 3 log10
IU/ml (99.9%) by Day 2. During the 3-day treatment period, mean maximal
HCV RNA reductions for the 4 dosing groups were:
3.2 log10 IU/mL in the 40 mg dose group
3.5 log10 IU/mL in the 80 mg dose group
3.5 log10 IU/mL in the 160 mg dose group
3.7 log10 IU/mL in the 240 mg dose group
mg dose group was found to be fully resistant at baseline with 100% of
this patient’s pre-treatment HCV RNA containing 3 genetically linked
NS5A resistance mutations. This patient was excluded from the efficacy
analysis of the 240 mg cohort, since he was pre-resistant and could not
contribute to dose-response inferences.
including those harboring the relatively common L31M variant, responded
well to PPI-668 treatment, with multi-log HCV RNA reductions.
clinical efficacy of PPI-668 in HCV genotype-2a/3a patients. Recruitment
is currently underway for this added cohort.
PPI-668 at the three higher dose levels and the encouraging safety
profile support advancement of PPI-668 to Phase 2 combination studies
with other promising HCV antiviral agents,” said Nathaniel A. Brown,
M.D., Presidio’s Chief Medical Officer.
“The PK profile of PPI-668
appears to be a major factor in its efficacy profile, with rapid
achievement of potentially effective plasma levels and with inter-dose
plasma concentrations exceeding those needed to inhibit both wild-type
HCV and many naturally-occurring HCV variants.”
a scientific meeting in the fall of 2012.