Phase 2a study met the primary endpoint of
safety and tolerability; numerical trends observed in endpoints in
the heart failure efficacy domains compared with placebo, including
increase in LVEF and patient reported outcomes
Results support further investigation of
AZD8601 for efficacy and safety in future larger studies
AZD8601 is being co-developed with
AstraZeneca
Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering
messenger RNA (mRNA) therapeutics and vaccines today announced
positive data from the AstraZeneca-led Phase 2 (EPICCURE) study
evaluating the use of an mRNA therapeutic that encodes for vascular
endothelial growth factor-A (VEGF-A) (AZD8601) in patients
undergoing coronary artery bypass grafting (CABG). These data were
presented today at the American Heart Association’s Scientific
Sessions 2021 annual meeting.
The Phase 2 study met the primary endpoint of safety and
tolerability of AZD8601. In the study of 11 patients, seven were
treated with AZD8601 VEGF-A mRNA and four received placebo
injections. Numerical trends were observed in endpoints in the
heart failure efficacy domains compared with placebo, including
increase in left ventricular ejection fraction (LVEF) and patient
reported outcomes. In addition, all seven patients treated with
AZD8601 had NT-proBNP levels below heart failure (HF) limit at 6
months follow-up compared to one of four patients treated with
placebo.
“mRNA is a compelling therapeutic modality because of its
ability to act locally and transiently, while driving
dose-dependent protein expression. We thank AstraZeneca for their
partnership and collaboration, which began in 2013, in advancing
this program,” said Stéphane Bancel, Chief Executive Officer of
Moderna. “The results presented today are a result of pushing new
boundaries in the treatment of cardiovascular and other ischemic
vascular diseases to address serious unmet needs with the goal of
improving patients’ lives.”
“Over one billion heart cells can be lost during a heart attack.
These early results indicate the potential of mRNA therapeutics in
stimulating VEGF-A production to provide reparative and
disease-modifying options for patients with heart failure and other
ischemic vascular diseases,” said Mene Pangalos, Executive Vice
President, BioPharmaceuticals R&D, AstraZeneca.
AZD8601 is an investigational, locally administered mRNA therapy
that encodes for VEGF-A. EPICCURE is a randomized,
placebo-controlled, double-blind, multicenter, 6-month, Phase 2a
clinical trial of the safety, tolerability, and exploratory
efficacy of epicardial injections of AZD8601 in patients with
stable coronary artery disease and moderately decreased LVEF who
are undergoing CABG surgery. Exploratory efficacy endpoints
included left ventricular ejection fraction, NT-proBNP (a biomarker
which measures the level of a hormone which is elevated in patients
with heart failure), and functional patient reported outcomes.
Coronary artery disease is caused by blockages in the main
coronary arteries and resulting insufficient blood flow to the
myocardium is the primary cause of ischemic heart failure. More
than 18.2 million adults older than 20 years of age in the U.S.
have coronary disease. And two in ten deaths from coronary disease
happen in adults younger than 65 years of age1. Coronary disease
can lead to myocardial infarction, which can lead to heart failure.
Additionally, chronic coronary artery disease, even without heart
attack, can lead to inadequate blood supply to part of the heart
and cause the muscle to not pump effectively, leading to heart
failure.
Heart failure affects approximately 40 million adults globally
and it is estimated that the prevalence will increase by 46% in the
next decade2. The prognosis of heart failure remains poor, with
mortality estimated at approximately 25-50% in patients at only
five years from diagnosis. Heart failure is also a burden on the
healthcare system, representing 2% to 3% of national health
expenditures in high-income countries, which is projected to double
in the next 20 years3.
About the Phase 2 Study of AZD8601
The Phase 2 study of AZD8601 is being conducted by AstraZeneca
and is evaluating safety and tolerability in patients with chronic
heart failure. Patients undergoing coronary artery bypass surgery
(CABG) with reduced left ventricular ejection fraction were
randomized to a series of epicardial injections in ischemic but
viable myocardium at the time of surgery with AZD8601 or placebo.
Study endpoints include safety and tolerability, as well as
exploratory efficacy endpoints including coronary blood flow, left
ventricular function, wall motion and overall cardiac function.
Clinical symptoms were evaluated through established quality of
life questionnaires as well as biomarkers including NT-proBNP,
markers known to be associated with cardiac prognosis. Patients
were followed for 6 months.
About Pre-Clinical & Phase 1 Studies of AZD8601
In an established porcine model of myocardial infarction, a
single epicardial administration of VEGF mRNA (AZD8601) ten days
after induced myocardial infarction improved left ventricular
ejection fraction at 2 months compared to placebo. In addition,
infarct size was significantly reduced. These and other preclinical
data supported advancement into clinical trials.
The Phase 1 study of AZD8601 evaluated safety and angiogenic
potential in men with Type 2 diabetes. Participants received
intradermal injections of AZD8601 or placebo at randomized sites on
their forearm, acting as their own controls. Intradermal VEGF-A
mRNA was well tolerated and led to local functional VEGF-A protein
expression 24 hours after administration as well as transient local
enhancement of basal skin blood flow at four hours and seven days
after administration. The results supported the suggestion that
AZD8601 has the potential for regenerative angiogenesis
About AZD8601
mRNA is responsible for carrying genetic instructions
transcribed from DNA, which cells then translate to produce
proteins. Proteins are responsible for directing the body’s
biological functions. Moderna’s mRNA therapeutics are designed to
trigger the cellular machinery to produce specific proteins. In
this application, AZD8601 may enable the delivery of genetic
instructions to spur the production of the paracrine factor
VEGF-A.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended, including regarding: the Company’s development in
collaboration with AstraZeneca of an mRNA therapeutic that encodes
for vascular endothelial growth factor-A (VEGF-A) (AZD8601) in
patients undergoing coronary artery bypass grafting (CABG); the
ability of AZD8601 to trigger an increase in left ventricular
ejection fraction (LVEF) and to improve patient outcomes; the
safety and tolerability of AZD8601; the conduct of future clinical
trials for AZD8601; and the disease burden associated with coronary
artery disease and heart failure. The forward-looking statements in
this press release are neither promises nor guarantees, and you
should not place undue reliance on these forward-looking statements
because they involve known and unknown risks, uncertainties, and
other factors, many of which are beyond Moderna’s control and which
could cause actual results to differ materially from those
expressed or implied by these forward-looking statements. These
risks, uncertainties, and other factors include those other risks
and uncertainties described under the heading “Risk Factors” in
Moderna’s most recent Annual Report on Form 10-K filed with the
U.S. Securities and Exchange Commission (SEC) and in subsequent
filings made by Moderna with the SEC, which are available on the
SEC’s website at www.sec.gov. Except as required by law, Moderna
disclaims any intention or responsibility for updating or revising
any forward-looking statements contained in this press release in
the event of new information, future developments or otherwise.
These forward-looking statements are based on Moderna’s current
expectations and speak only as of the date hereof.
_____________________
1
https://www.cdc.gov/heartdisease/statistics_maps.htm
2
https://pubmed.ncbi.nlm.nih.gov/28527533/
3
https://pubmed.ncbi.nlm.nih.gov/23616602/
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Moderna Contacts
Media: Colleen Hussey Director, Corporate Communications
Colleen.Hussey@modernatx.com (617) 335-1374
Investors: Lavina Talukdar Senior Vice President &
Head of Investor Relations Lavina.Talukdar@modernatx.com (617)
209-5834
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