Prothena Reports Results from Phase 1b Study of PRX002 Demonstrating Robust Antibody CNS Penetration and Significant Reduction of Free Serum Alpha-synuclein in Patients with Parkinson's Disease
(Thomson Reuters ONE) -
* All dose levels of PRX002 found to have an acceptable safety and
tolerability profile, meeting the primary objective of this study
* Robust central nervous system (CNS) penetration demonstrated by a dose-
dependent increase in PRX002 levels in cerebrospinal fluid (CSF), and mean
concentration of PRX002 in CSF of 0.3 percent relative to serum across all
dose levels
* Rapid, dose- and time-dependent mean reduction in levels of free serum
alpha-synuclein of up to 97 percent
* Data supports advancing PRX002 into Phase 2 clinical study, planned for 2017
DUBLIN, Ireland, Nov. 09, 2016 (GLOBE NEWSWIRE) -- Prothena Corporation plc
(Nasdaq:PRTA), a late-stage clinical biotechnology company focused on the
discovery, development and commercialization of novel protein immunotherapies,
today announced results from its Phase 1b multiple ascending dose study of
PRX002, an antibody under investigation as a potentially disease-modifying
treatment for Parkinson's disease. PRX002, also known as RG7935, is the focus of
a worldwide collaboration between Prothena and Roche.
PRX002 was found to have an acceptable safety and tolerability profile in
patients with Parkinson's disease, meeting the primary objective of this study.
Robust CNS penetration was demonstrated by a dose-dependent increase in PRX002
levels in CSF, and a mean concentration of PRX002 in CSF of 0.3 percent relative
to serum across all dose levels. Additional results showed a rapid, dose- and
time dependent mean reduction of free serum alpha-synuclein levels of up to 97
percent after a single dose, which were statistically significant (p < 0.0001),
and confirmed after two additional monthly doses.
"These data represent the first reported assessment of an anti-alpha-synuclein
antibody in patients with Parkinson's disease," stated Gene Kinney, PhD,
President and Chief Executive Officer of Prothena. "In this study we observed
PRX002 penetration in the CNS that exceeded our expectations based on our
preclinical experience, and a highly statistically significant reduction of free
serum alpha-synuclein. These Phase 1b data further support our belief that we
can choose doses that target and saturate aggregated pathogenic alpha-synuclein
in the brain for a Phase 2 study to further explore the potential of PRX002 as a
disease-modifying treatment for Parkinson's disease. Together with Roche, we
expect to initiate a Phase 2 study in 2017."
This Phase 1b double-blind, placebo-controlled multiple ascending dose study
enrolled 80 patients with Parkinson's disease. Patients were randomized into six
escalating dose cohorts to receive PRX002 or placebo (2:1 randomization for
0.3, 1, 3 or 10 mg/kg, and 3:1 randomization for 30 or 60 mg/kg). In this six-
month study, patients received three monthly doses (intravenous infusion once
every 28 days) of PRX002 or placebo and were followed for an observational
period of three months. No serious or severe treatment emergent adverse events
(TEAEs) were reported in PRX002 treated patients. No TEAEs were observed in ten
percent or more of PRX002 treated patients. TEAEs greater than placebo in five
percent or more of PRX002 treated patients, regardless of relationship to
PRX002, included constipation, infusion related reactions (IRRs), diarrhoea,
peripheral oedema, and post lumbar puncture syndrome. Mild-to-moderate IRRs,
that all resolved, were limited to the 60 mg/kg dose cohort and were observed in
four of 12 treated patients. No dose-limiting toxicities were observed. PRX002
demonstrated acceptable pharmacokinetic properties.
"Developing new therapies for complex neurological diseases such as Parkinson's
requires dedicated and disciplined science," said Todd Sherer, PhD, CEO of The
Michael J. Fox Foundation for Parkinson's Research. "Targeting alpha-synuclein
represents a promising path toward a potentially disease-modifying treatment for
Parkinson's disease, and we are very pleased to see PRX002 advance to the next
stage of development."
Prothena plans to present results from this study at an upcoming scientific
conference. A Phase 2 clinical study is expected to begin in 2017.
About Alpha-synuclein
Alpha-synuclein is a protein found in neurons and is a major component of
pathology that characterizes several neurodegenerative disorders including
Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy,
which collectively are termed synucleinopathies. While the normal function of
alpha-synuclein is not well understood, the protein generally occurs in a
soluble form. In synucleinopathies, the alpha-synuclein protein can misfold and
aggregate to form soluble aggregates and insoluble fibrils that contribute to
disease pathology. There is increasing evidence that this disease-causing alpha-
synuclein can be propagated and transmitted from neuron to neuron, resulting in
an infection-like spread of neuronal death. Recent studies in cellular and
animal models suggest that the spread of alpha-synuclein-associated
neurodegeneration can be disrupted by targeting aberrant forms of alpha-
synuclein.
About PRX002 (RG7935)
PRX002 is a monoclonal antibody under development for the potential treatment of
Parkinson's disease. PRX002 targets alpha-synuclein and is designed to slow the
progressive neurodegeneration associated with alpha-synuclein misfolding and/or
the cell-to-cell transmission of the aggregated pathogenic forms of alpha-
synuclein found in Parkinson's disease and other synucleinopathies. Prior to
initiating clinical trials, Prothena demonstrated the efficacy of PRX002 in
various cellular and animal models of alpha-synuclein-related disease. In
multiple transgenic mouse models of Parkinson's disease, passive immunization
with 9E4, the murine version of PRX002, reduced the appearance of alpha-
synuclein pathology, protected synapses and improved performance in behavioral
testing. In December 2013 Prothena and Roche entered into a worldwide
collaboration to develop and commercialize antibodies that target alpha-
synuclein, including PRX002. Prothena has an option to co-promote PRX002 in the
U.S., where the companies share all development and commercialization costs, as
well as profits, on a 30/70 basis (30 percent Prothena, 70 percent Roche).
Outside the U.S., Roche will have sole responsibility for developing and
commercializing PRX002 and will pay Prothena up to double-digit royalties on net
sales. A Phase 2 clinical study of PRX002 in patients with Parkinson's disease
is expected to begin in 2017.
About Parkinson's Disease
Parkinson's disease is a progressive degenerative disorder of the central
nervous system (CNS) that affects one in 100 people over age 60. With an
estimated seven to 10 million patients living with Parkinson's disease
worldwide, it is the second most common neurodegenerative disorder after
Alzheimer's disease. The disease is characterized by the neuronal accumulation
of aggregated alpha-synuclein in the CNS and peripheral nervous system that
results in a wide spectrum of worsening progressive motor and non-motor
symptoms. While diagnosis relies on motor symptoms classically associated with
Parkinson's disease, non-motor symptoms may present many years earlier. Current
treatments for Parkinson's disease are symptomatic and only address a subset of
symptoms such as motor impairment, dementia, or psychosis. Symptomatic therapies
do not target the underlying cause of the disease and lose effectiveness, often
leading to debilitating side effects as the disease progresses.
About Prothena
Prothena Corporation plc is a global, late-stage clinical biotechnology company
seeking to fundamentally change the course of progressive diseases with its
clinical pipeline of novel therapeutic antibodies. Fueled by its deep scientific
understanding built over decades of research in protein misfolding and cell
adhesion - the root causes of many serious or currently untreatable amyloid and
inflammatory diseases - Prothena is establishing a fully integrated research,
development and commercial focus and has advanced several drug candidates into
clinical studies while pursuing discovery of additional novel therapies. Our
pipeline of antibody-based product candidates targets a number of potential
indications including AL amyloidosis (NEOD001), Parkinson's disease and other
related synucleinopathies (PRX002), inflammatory diseases, including psoriasis
and psoriatic arthritis (PRX003), and ATTR amyloidosis (PRX004). For more
information, please visit the company's website at www.prothena.com.
Forward-Looking Statements
This press release contains forward-looking statements. These statements relate
to, among other things, plans for and the timing of initiating a Phase 2
clinical study of PRX002; our ability to choose appropriate doses for that Phase
2 study; and the potential of PRX002 as a disease modifying treatment for
Parkinson's disease. These statements are based on estimates, projections and
assumptions that may prove not to be accurate, and actual results could differ
materially from those anticipated due to known and unknown risks, uncertainties
and other factors, including but not limited to the risks, uncertainties and
other factors described in the "Risk Factors" sections of our Annual Report on
Form 10-K filed with the Securities and Exchange Commission (SEC) on February
25, 2016 and our subsequent Quarterly Reports on Form 10-Q filed with the SEC.
Prothena undertakes no obligation to update publicly any forward-looking
statements contained in this press release as a result of new information,
future events or changes in Prothena's expectations.
Contacts:
Investors: Tran Nguyen, CFO
650-837-8535, IR(at)prothena.com
Media: Ellen Rose, Head of Communications
650-922-2405, ellen.rose(at)prothena.com
This announcement is distributed by Nasdaq Corporate Solutions on behalf of Nasdaq Corporate Solutions clients.
The issuer of this announcement warrants that they are solely responsible for the content, accuracy and originality of the information contained therein.
Source: Prothena Corporation plc via GlobeNewswire
Unternehmensinformation / Kurzprofil:
Datum: 09.11.2016 - 22:05 Uhr
Sprache: Deutsch
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