Demonstrated Effectiveness Across All
Disease Parameters Including Cardiac and Kidney
Functions
Protalix BioTherapeutics, Inc. (NYSE:PLX) (TASE:PLX), announced
today that positive interim data from the Company's phase I/II
dose-ranging clinical trial of PRX-102 for the treatment of Fabry
disease will be presented on March 3, 2016 at 3:15 PM PT at the
Lysosomal Disease Network 12th Annual WORLDSymposium 2016 in San
Diego, CA. PRX-102 is a recombinant plant cell expressed,
Pegylated modified version of the human alpha-Galactosidase-A
enzyme. A slide presentation featuring these data will be
posted at the time of the presentation on the Company's web site,
under the Presentations tab.
"PRX-102 has the potential to be a meaningful treatment for
patients suffering from Fabry disease," said Dr Derralynn Hughes,
Senior Lecturer in Hematology at the Royal Free & University
College Medical School and Director of the lysosomal storage
disorders research program, and Principal Investigator in the
clinical trial. "The pharmacokinetic data and scientific
rationale behind why PRX-102 has the potential to be next
generation enzyme replacement therapy is supported by the current
Phase I/II efficacy and safety data. I look forward to
collaborating with Protalix as the Company moves into
Phase III development."
Dr. Hughes will be presenting interim results from the global,
open-label, phase I/II dose-ranging trial. In the trial, 18
naïve male and female patients (11 male and 7 female) were enrolled
across three dosing cohorts of 0.2 mg/kg, 1mg/kg and 2mg/kg for
which intravenous infusions were administered every two weeks, with
six and twelve month initial efficacy follow-ups.
Clinical Data on Cardiac and Kidney
Functions
Based on an analysis of kidney biopsies with randomized blinded
scoring, PRX-102 demonstrated a major reduction from baseline in
renal peritubular capillary Gb3 using the quantitative Barisoni
Lipid Inclusion Scoring System (BLISS). The following table
denotes the mean change from baseline at six months.
|
|
|
0.2 mg/kg Dosing Cohort |
|
Percentage Reduction of Gb3 |
Overall (n=5) |
|
|
75.5 |
% |
Male (n=3) |
|
|
82.2 |
% |
Female (n=2) |
|
|
65.4 |
% |
|
|
|
1.0 mg/kg Dosing Cohort |
|
Percentage Reduction of Gb3 |
Overall (n=4) |
|
|
86.5 |
% |
Male (n=3) |
|
|
89.6 |
% |
Female (n=1) |
|
|
77.3 |
% |
|
|
|
|
|
In general, the leading causes for death of Fabry patients
include cardiovascular disease and renal failures. All
patients that participated in the trial exhibited stable cardiac
and kidney function as measured by mean left ventricular mass
(LVM), left ventricular mass index (LVMI), ejection fraction (EF),
estimated Glomerular filtration rate (eGFR) and urine protein.
The table below sets forth the mean absolute values, at
baseline, six and twelve months of treatment, including percentage
changes, which were scored in a randomized blinded manner.
|
|
|
|
|
|
|
|
0.2
mg/kg Dosing Cohort |
|
|
|
|
|
|
|
Timeframe |
|
LVM
(gr) |
|
LVMI
(gr/m2) |
|
EF
(%) |
|
eGFR
(mL/min/1.73m2) |
|
Urine
Protein (mg/g creatinine) |
Baseline |
|
98 |
|
55.1 |
|
55.1 |
|
109.1 |
|
185.3 |
6 months |
|
94.4 |
|
52.6 |
|
55.8 |
|
108.5 |
|
193.3 |
12 months |
|
94.8 |
|
53 |
|
54.6 |
|
111.8 |
|
176.7 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1.0
mg/kg Dosing Cohort |
|
|
|
|
|
|
|
Timeframe |
|
LVM
(gr) |
|
LVMI
(gr/m2) |
|
EF
(%) |
|
eGFR
(mL/min/1.73m2) |
|
Urine
Protein (mg/g creatinine) |
Baseline |
|
104.1 |
|
55.8 |
|
62.6 |
|
104.8 |
|
92.2 |
6 Months |
|
101.1 |
|
54.1 |
|
57.4 |
|
106.6 |
|
101.2 |
|
|
|
|
|
|
|
|
|
|
|
Mean annualized eGFR slope for male patients was found to be
0.16 for the 0.2mg/kg and 0.72 for the 1.0mg/kg. The
reduction in the eGFR slope suggests that PRX-102 has the potential
to attenuate the symptoms experienced by patients suffering from
renal disease, and may introduce other potential benefits to those
patients.
Reductions of plasma Lyso-Gb3 and plasma Gb3 concentrations were
also observed at six months. For the 0.2 mg/kg
cohort, males (n=4) demonstrated a -72.2 ng/mL and a -3.9
µg/mL change, respectively. For the 1.0 mg/kg cohort, males
(n=4) demonstrated a -67.6 ng/mL and a -5.4 µg/mL change,
respectively.
A meaningful reduction in the total score of Mainz Severity
Score Index (MSSI), which looks at general, neurological,
cardiovascular and renal parameters, was demonstrated in both the
0.2 and 1.0 mg/kg dosing cohorts at six months.
Safety Data
The safety analysis for adverse events represents a total of
approximately 15 patient years (n=18). PRX-102 was well
tolerated, with the majority of events being mild and
moderate. Only one of the 18 patients evaluated for safety
experienced a related serious adverse event of hypersensitivity and
was discontinued per protocol.
There was a low incidence of treatment-induced anti-drug
antibodies (ADA) with low titers that are reduced by one year of
treatment. Only 3 out of 18 patients had treatment induced
ADA in at least one visit (2 in the 0.2mg/kg dose group; one in the
1mg/kg dose group). Two patients of the 0.2mg/kg dose group
had neutralizing antibodies, 1 of which was positive only in 2 out
of 8 samples.
Overall, PRX-102 showed a favorable trend in kidney function,
stable cardiac function and reduction in kidney peritubular
capillaries, plasma Gb3, Lyso-Gb3 and MSSI score.
Enrollment in the phase I/II clinical trial of PRX-102 was
completed in February 2015. All patients that completed the
trial opted to continue to receive PRX-102 in an open-label
extension study. The Company expects to report data on the
2mg/kg dose and additional interim 12 month data and full 24
clinical trial results throughout 2016 and 2017 at various medical
meetings and symposia.
The Company filed a Special Protocol Assessment (SPA) with the
FDA for its planned phase III trial and expects to commence the
trial in the first half of 2016.
About Protalix BioTherapeutics, Inc.
Protalix is a biopharmaceutical company focused on the
development and commercialization of recombinant therapeutic
proteins expressed through its proprietary plant cell-based
expression system, ProCellEx(R). Protalix's unique expression
system presents a proprietary method for developing recombinant
proteins in a cost-effective, industrial-scale manner. Protalix's
first product manufactured by ProCellEx, taliglucerase alfa, was
approved for marketing by the U.S. Food and Drug Administration
(FDA) in May 2012 and, subsequently, by the regulatory authorities
of other countries. Protalix has licensed to Pfizer Inc. the
worldwide development and commercialization rights for
taliglucerase alfa, excluding Brazil, where Protalix retains full
rights. Protalix's development pipeline includes the
following product candidates: PRX-102, a modified version of the
recombinant human alpha-GAL-A protein for the treatment of Fabry
disease; PRX-106, an orally-delivered anti-inflammatory treatment;
PRX-110 for the treatment of Cystic Fibrosis; and others.
Forward-Looking Statements
To the extent that statements in this press release are not
strictly historical, all such statements are forward-looking, and
are made pursuant to the safe-harbor provisions of the Private
Securities Litigation Reform Act of 1995. The terms
“anticipate,” “believe,” “estimate,” “expect,” “plan” and “intend”
and other words or phrases of similar import are intended to
identify forward-looking statements. These forward-looking
statements are subject to known and unknown risks and uncertainties
that may cause actual future experience and results to differ
materially from the statements made. These statements are
based on our current beliefs and expectations as to such future
outcomes. Drug discovery and development involve a high
degree of risk. Factors that might cause material differences
include, among others: failure or delay in the commencement or
completion of our preclinical and clinical trials which may be
caused by several factors, including: slower than expected rates of
patient recruitment; unforeseen safety issues; determination of
dosing issues; lack of effectiveness during clinical trials;
inability to monitor patients adequately during or after treatment;
inability or unwillingness of medical investigators and
institutional review boards to follow our clinical protocols; and
lack of sufficient funding to finance clinical trials; the risk
that the results of the clinical trials of our product candidates
will not support our claims of safety or efficacy, that our product
candidates will not have the desired effects or will be associated
with undesirable side effects or other unexpected characteristics;
our dependence on performance by third party providers of services
and supplies, including without limitation, clinical trial
services; delays in our preparation and filing of applications for
regulatory approval; delays in the approval or potential rejection
of any applications we file with the FDA or other health regulatory
authorities, and other risks relating to the review process; the
inherent risks and uncertainties in developing drug platforms and
products of the type we are developing; the impact of development
of competing therapies and/or technologies by other companies and
institutions; potential product liability risks, and risks of
securing adequate levels of product liability and other necessary
insurance coverage; and other factors described in our filings with
the U.S. Securities and Exchange Commission. The statements
in this release are valid only as of the date hereof and we
disclaim any obligation to update this information.
Investor Contact
Marcy Nanus
The Trout Group, LLC
646-378-2952
mnanus@troutgroup.com
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