Prothena Presents New Research Supporting Clinical Relevance of Cardiac Biomarker NT-proBNP in AL Amyloidosis
(Thomson Reuters ONE) -
* 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(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: 18.09.2017 - 14:00 Uhr
Sprache: Deutsch
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