(By Balaseshan) Dynavax Technologies Corp. (NASDAQ:DVAX : 4.4, 0.24) said the Food and Drug Administration (FDA) has accepted for review the U.S. Biologics License Application (BLA) of its investigational adult hepatitis B vaccine.
The company anticipates submitting a European Marketing Authorization Application (MAA) for HEPLISAV in the third quarter of 2012.
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SAN FRANCISCO, Jun 26, 2012 (BUSINESS WIRE) —
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
The randomized, blinded Phase 1b trial of PPI-668 involved sequential
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.
In all of the Phase 1b dose cohorts, PPI-668 was well tolerated with no
serious or severe adverse events, no premature treatment
discontinuations and no apparent pattern of treatment-related clinical
side effects or laboratory abnormalities.
The Phase 1 clinical results indicate that PPI-668 had a favorable
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
There was only one minimal-responder in the trial. A patient in the 240
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.
Five other patients with detectable resistance mutations at baseline,
including those harboring the relatively common L31M variant, responded
well to PPI-668 treatment, with multi-log HCV RNA reductions.
A protocol amendment has been completed to explore the pan-genotypic
clinical efficacy of PPI-668 in HCV genotype-2a/3a patients. Recruitment
is currently underway for this added cohort.
“The rapid 3.5 to 3.7 log10 HCV RNA reductions observed with
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.”
Detailed results of the completed trial are expected to be presented at
a scientific meeting in the fall of 2012.
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