YASTEST
- Preclinical Research Demonstrating a Direct Relationship
Between Misfolded Light Chain Toxicity and NT-proBNP
Production
- Clinical Outcomes Research Showing a Correlation between
NT-proBNP Response and Health-related Quality of
Life
- Data Presented at Heart Failure Society of America Annual
Meeting
DUBLIN, Ireland, Sept. 18, 2017
(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 highlighted research from two new studies being presented at
the Heart Failure Society of America (HFSA) Annual Scientific
Meeting in Dallas, Texas that further supports the important role
of the cardiac biomarker NT-proBNP in both the biology and clinical
aspects of AL amyloidosis. Preclinical data presented in a
moderated poster talk and poster session at the
conference demonstrated the relationship between misfolded light
chain toxicity to heart cells and production of NT-proBNP. In
addition, a clinical outcomes study also presented by
Prothena showed a correlation between NT-proBNP response and
quality of life measures in patients who have AL amyloidosis with
cardiac involvement. NT-proBNP is a cardiac biomarker that has been
shown in multiple independent studies to predict survival in
patients with AL amyloidosis (Merlini, et. al, Leukemia, 2016).
"These results provide new
insights into the important role of NT-proBNP in AL amyloidosis,
unique from other forms of heart failure, and offer further support
for the clinical utility of NT-proBNP as a surrogate biomarker in
AL amyloidosis studies," said Sarah Noonberg, MD, Ph.D., Chief
Medical Officer of Prothena. "Furthermore, data from our clinical
outcomes research demonstrate a clinically meaningful relationship
between NT-proBNP response and quality of life improvements that
are highly relevant to patients, and will be further evaluated in
our two late-stage studies of NEOD001."
New preclinical research supports relationship between
lowering of NT-proBNP and improved survival in patients with AL
amyloidosis
New preclinical research presented
at HFSA provides mechanistic insight into how misfolded light
chains induce cardiotoxicity and increase NT-proBNP production.
Prothena's research demonstrated that aggregated light chain
induces oxidative stress and leads to an increase in expression of
the oxidative response marker heme oxygenase-1 (Hmox-1) in
cardiomyocytes. The research further showed that NT-proBNP
secretion is increased by aggregated light chain, via a mechanism
dependent on Hmox-1 catalytic activity. Aggregated light chain
exhibited dose-dependent binding to cardiomyocytes, suggesting that
the observed effect is driven by the direct interaction between
aggregated light chains and cardiomyocytes.
Taken together, these results
support the finding that aggregated light chain induces
cardiomyocyte toxicity and provides a direct link between the
misfolded protein and NT-proBNP elevation in AL amyloidosis.
Furthermore, these data indicate
that the role of NT-proBNP in AL amyloidosis is differentiated from
other forms of heart failure, and support the relationship that has
been reported between lowering of NT-proBNP and improved cardiac
function and survival in patients with AL amyloidosis.
Clinical outcomes research demonstrates NT-proBNP response
is associated with clinically meaningful improvements in
health-related quality of life in patients with AL
amyloidosis
New clinical outcomes research
also presented by Prothena at HFSA establishes for the first time a
correlation between NT-proBNP response and health-related quality
of life measures. In this study, data were extracted from a
community-based sample of 108 patients with AL amyloidosis and
validated against patient health records from an AL amyloidosis
Center of Excellence (COE) sample of 95 patients. All patients in
both samples had AL amyloidosis with cardiac involvement. Patients'
health-related quality of life was evaluated using the
SF-36® Health
Survey for eight domains of functional health and well-being that
provided two summary scores, one physical and one mental. Patients
in the community-based sample were also evaluated by the Kansas
City Cardiomyopathy Questionnaire - Short Form (KCCQ-12), a
validated health-related quality of life measure that is specific
to heart failure.
In the community-based sample
(n=108), cardiac response was defined as a 30 percent or greater
decrease in NT-proBNP. Differences in SF-36 scores for patients
with and without a previous response in NT-proBNP were
statistically significant (p<0.05 for all domains and both
summary scores) and clinically meaningful. In addition, patients
with a history of cardiac response reported SF-36 scores that were
significantly better than existing congestive heart failure (CHF)
benchmarks across all SF-36 domains and both summary
components.
Differences in burden of disease
as measured by KCCQ-12 scores for patients with and without
previous NT-pro-BNP response were also statistically significant (p
< 0.05 for all subscales). The average total KCCQ-12 score for
patients with a history of NT-proBNP response (n=75) was 66, which
corresponds to scores previously observed in patients with New York
Heart Association (NYHA) functional class II symptoms, indicating
slight limitation in physical activity. The average score for
patients with no history of NT-proBNP response (n=33) was 42, which
corresponds to scores previously observed in patients with NYHA
functional class III symptoms, indicating a marked limitation in
physical activity.
Results from the AL amyloidosis
Center of Excellence validation patient cohort (n=95) showed
comparable findings.
This study demonstrates the
relationship between the cardiac biomarker NT-proBNP with
health-related quality of life using multiple data sources and
different analytic approaches. The data further support that
NT-proBNP may be a useful surrogate measure for health-related
quality of life and burden of disease classification of
patients.
About NEOD001
NEOD001 is an investigational
first-in-class antibody that specifically targets disease-causing
misfolded light chain aggregates in AL amyloidosis. There are two
ongoing global clinical studies for NEOD001. The PRONTO study, a
global, Phase 2b, double-blind, placebo-controlled,
registration-directed study, will evaluate NEOD001 vs. placebo in
previously-treated patients with AL amyloidosis and persistent
cardiac dysfunction, and will assess best response over 12 months
of the cardiac biomarker NT-proBNP, defined by the consensus
criteria of NT-proBNP change, in addition to other biomarker,
quality of life and functional endpoints. The VITAL
Amyloidosis Study, a global, Phase 3, double-blind,
placebo-controlled, registrational study, is evaluating NEOD001 vs.
placebo in newly-diagnosed, treatment-naïve patients with AL
amyloidosis and cardiac dysfunction, with both arms of the study
receiving standard of care. The VITAL study will assess a composite
endpoint of all-cause mortality or cardiac hospitalizations in
addition to biomarker, quality of life and functional endpoints.
More information on the PRONTO study and The VITAL Amyloidosis
Study is available at www.clinicaltrials.gov, by searching NCT
#02632786 for PRONTO, and NCT #02312206 for VITAL
or www.clinicaltrialsregister.eu, by searching
EudraCT #2015-004318-14 for PRONTO, and EudraCT
#2014-003865-11 for VITAL.
About AL Amyloidosis
Systemic amyloidoses are a complex
group of diseases caused by tissue deposition of misfolded proteins
that result in progressive organ damage. AL amyloidosis, the most
common type, is a rare, progressive, and typically fatal disease
caused by extracellular deposition of misfolded immunoglobulin
light chains. An excess of light chains prone to misfolding are
produced by clonal plasma cells. Soluble toxic aggregates and
deposited fibrils (amyloid) lead to progressive failure of vital
organs including the heart, kidneys and nervous system, causing
significant morbidity and mortality. It is estimated that
approximately 30,000 - 45,000 patients in the U.S. and Europe
suffer from this disease. There are no approved treatments for AL
amyloidosis, although patients may be treated with off-label
therapies directed at the plasma cell dyscrasia. There is a large
unmet need for therapies that specifically target soluble toxic
aggregates and deposited fibrils, thereby improving vital organ
function. For more information on AL amyloidosis, please visit the
websites of the Amyloidosis Support Groups, The
Amyloidosis Research Consortium, and the Amyloidosis
Foundation.
About Prothena
Prothena Corporation plc is a
global, late-stage clinical biotechnology company establishing
fully-integrated research, development and commercial capabilities.
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 seeks to fundamentally change the course of
progressive diseases associated with this biology. The Company's
pipeline of antibody therapeutic candidates targets a number of
indications including AL amyloidosis (NEOD001), Parkinson's disease
and other related synucleinopathies (PRX002/RG7935), inflammatory
diseases, including psoriasis and psoriatic arthritis (PRX003), and
ATTR amyloidosis (PRX004). The Company continues discovery of
additional novel therapeutic candidates where its deep scientific
understanding of disease pathology can be leveraged. 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, the
relationship between misfolded light chain toxicity and NT-proBNP
production; the correlation between NT-proBNP response and
health-related quality of life; whether aggregated light chain
induces cardiomyocyte toxicity; the clinical utility of NT-proBNP
as a surrogate biomarker in AL amyloidosis; and the correlation
between lowering of NT-proBNP and improved cardiac function and
survival in patients with AL amyloidosis. 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 27, 2017 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.
Media & Investor Contact:
Ellen Rose, Head of
Communications
650-922-2405, ellen.rose@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
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