– KARDIA-1 will Evaluate Efficacy and Safety of
Quarterly and Biannual Regimens of Zilebesiran as Monotherapy –
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, today announced initiation of KARDIA-1, a
global Phase 2 study evaluating the efficacy and safety of
zilebesiran (pronounced “zile-BEE-siran” and formerly known as
ALN-AGT), an investigational subcutaneous RNAi therapeutic
targeting liver-expressed angiotensinogen (AGT) in development for
the treatment of hypertension. KARDIA-1 will evaluate zilebesiran
as monotherapy across different doses administered quarterly and
biannually. The Company will host an “RNAi Roundtable” webinar
today at 10:00 a.m. ET to discuss the zilebesiran program.
The primary endpoint of KARDIA-1 is the change from baseline in
systolic blood pressure as measured by 24-hour ambulatory blood
pressure monitoring after three months of treatment. Additional
endpoints will include change from baseline in blood pressure at
six months, time-averaged reduction of blood pressure as a measure
of tonic control, and safety. The study initiation is based on
encouraging Phase 1 data, including results presented earlier this
year at the 2021 Joint Meeting of the European Society of
Hypertension (ESH) and the International Society of Hypertension
(ISH). KARDIA-1 has been activated at clinical sites in the U.S.
and will also be conducted at sites in Europe.
“According to the World Health Organization, hypertension is the
largest modifiable risk factor for cardiovascular morbidity and
mortality. Despite the availability of numerous anti-hypertensive
medications, tonic control of blood pressure remains elusive and
represents a major unmet need, elevating the risk of fatal and
nonfatal cardiovascular events, primarily stroke and heart attack.
In addition, lack of patient adherence to therapy with daily oral
medications further contributes to the challenges of inadequate
blood pressure control,” said Weinong Guo, M.D., Ph.D., Senior Vice
President of Clinical Development at Alnylam. “The initiation of
KARDIA-1, along with the planned start of the KARDIA-2 Phase 2
study later this year, signifies Alnylam’s commitment to advance
zilebesiran as a potential treatment to help address the worldwide
burden of uncontrolled hypertension.”
Additional details about the RNAi Roundtable can be found on the
Capella section of the Company’s website here.
About KARDIA-1 Phase 2 Study
The KARDIA-1 Phase 2 trial is a randomized, double-blind (DB),
placebo-controlled, dose-ranging study to evaluate the efficacy and
safety of zilebesiran as monotherapy in adults with
mild-to-moderate hypertension. This global, multicenter trial will
enroll approximately 375 adults with untreated hypertension or who
are on stable therapy with one or more anti-hypertensive
medications. Any patients taking prior anti-hypertensive
medications will complete at least a four-week wash-out before
randomization. Study participants will be randomized to one of five
treatment arms during a 12-month DB period and DB extension period:
1) 150 mg zilebesiran subcutaneously once every six months; 2) 300
mg zilebesiran subcutaneously once every six months; 3) 300 mg
zilebesiran subcutaneously once every three months; 4) 600 mg
zilebesiran subcutaneously once every six months; or 5) placebo.
Patients who receive placebo will be randomized to one of the four
initial zilebesiran dose regimens beginning at month six. The
study’s primary efficacy endpoint is the change from baseline in
systolic blood pressure, assessed by 24-hour ambulatory blood
pressure monitoring, after three months of treatment. In addition
to the evaluation of the safety of zilebesiran, key secondary and
exploratory endpoints in this study include additional measures of
blood pressure reduction at six months, time-adjusted change in
blood pressure, and change in daytime average and night-time
average blood pressure. For more information on KARDIA-1
(NCT04936035), please visit clinicaltrials.gov, email
clinicaltrials@alnylam.com or call 877-256-9526 in North America
and +31 20 369 7861 in Europe.
About Zilebesiran
Formerly known as ALN-AGT, zilebesiran (pronounced
“zile-BEE-siran”) is an investigational, subcutaneously
administered RNAi therapeutic targeting angiotensinogen (AGT) in
development for the treatment of hypertension in high unmet need
populations. AGT is the most upstream precursor in the
Renin-Angiotensin-Aldosterone System (RAAS), a cascade which has a
demonstrated role in blood pressure regulation and its inhibition
has well-established anti-hypertensive effects. Zilebesiran
inhibits the synthesis of AGT in the liver, potentially leading to
durable reductions in AGT protein and ultimately, in the
vasoconstrictor angiotensin (Ang) II. Zilebesiran utilizes
Alnylam's Enhanced Stabilization Chemistry Plus (ESC+)
GalNAc-conjugate technology, which enables subcutaneous dosing with
increased selectivity and a wide therapeutic index. The safety and
efficacy of zilebesiran have not been established or evaluated by
the FDA, EMA or any other health authority.
About Hypertension
Hypertension is a complex multifactorial disease clinically
defined by most major guidelines as a systolic blood pressure (SBP)
of above 140 mm Hg and/or a diastolic blood pressure (DBP) greater
than 90 mm Hg, though AHA/ACC guidelines have a lower threshold of
a SBP above 130 mm Hg and/or a DBP greater than 80 mm Hg. More than
one billion people worldwide live with hypertension.i In the U.S.
alone, approximately 47 percent of adults live with hypertension,
with more than half of patients on medication remaining above the
blood pressure target level. Despite the availability of
anti-hypertensive medications, there remains a significant unmet
medical need, especially given the poor rates of adherence to
existing daily oral medications and daily peak and trough effects,
resulting in inconsistent blood pressure control and an increased
risk for stroke, heart attack and premature death.ii In particular,
there are a number of high unmet need settings where novel
approaches to hypertension warrant additional development focus,
including patients with poor medication adherence,
difficult-to-treat and resistant hypertension, and in patients with
high cardiovascular risk.
About RNAi
RNAi (RNA interference) is a natural cellular process of gene
silencing that represents one of the most promising and rapidly
advancing frontiers in biology and drug development today. Its
discovery has been heralded as “a major scientific breakthrough
that happens once every decade or so,” and was recognized with the
award of the 2006 Nobel Prize for Physiology or Medicine. By
harnessing the natural biological process of RNAi occurring in our
cells, a new class of medicines, known as RNAi therapeutics, is now
a reality. Small interfering RNA (siRNA), the molecules that
mediate RNAi and comprise Alnylam’s RNAi therapeutic platform,
function upstream of today’s medicines by potently silencing
messenger RNA (mRNA) – the genetic precursors – that encode for
disease-causing proteins, thus preventing them from being made.
This is a revolutionary approach with the potential to transform
the care of patients with genetic and other diseases.
About Alnylam Pharmaceuticals
Alnylam (Nasdaq: ALNY) is leading the translation of RNA
interference (RNAi) into a whole new class of innovative medicines
with the potential to transform the lives of people afflicted with
rare genetic, cardio-metabolic, hepatic infectious, and central
nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning
science, RNAi therapeutics represent a powerful, clinically
validated approach for the treatment of a wide range of severe and
debilitating diseases. Founded in 2002, Alnylam is delivering on a
bold vision to turn scientific possibility into reality, with a
robust RNAi therapeutics platform. Alnylam’s commercial RNAi
therapeutic products are ONPATTRO® (patisiran), GIVLAARI®
(givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran) being
developed and commercialized by Alnylam’s partner Novartis. Alnylam
has a deep pipeline of investigational medicines, including six
product candidates that are in late-stage development. Alnylam is
executing on its “Alnylam P5x25” strategy to deliver transformative
medicines in both rare and common diseases benefiting patients
around the world through sustainable innovation and exceptional
financial performance, resulting in a leading biotech profile.
Alnylam is headquartered in Cambridge, MA. For more information
about our people, science and pipeline, please visit
www.alnylam.com and engage with us on Twitter at @Alnylam, on
LinkedIn, or on Instagram.
Alnylam Forward Looking Statements
Various statements in this release concerning Alnylam’s
expectations, plans, aspirations, and goals, including those
related to encouraging results from our Phase 1 study of
zilebesiran (formerly known as ALN-AGT), the design and conduct of
our KARDIA-1 Phase 2 study of zilebesiran and the planned
activation of the study at sites in Europe following U.S.
initiation, our commitment to advancing zilebesiran as a potential
[treatment to help] address the worldwide burden of uncontrolled
hypertension, our aspiration to become a leading biotech company,
and the planned achievement of our “Alnylam P5x25” strategy,
constitute forward-looking statements for the purposes of the safe
harbor provisions under The Private Securities Litigation Reform
Act of 1995. Actual results and future plans may differ materially
from those indicated by these forward-looking statements as a
result of various important risks, uncertainties and other factors,
including, without limitation: the direct or indirect impact of the
COVID-19 global pandemic or any future pandemic on Alnylam’s
business, results of operations and financial condition and the
effectiveness or timeliness of Alnylam’s efforts to mitigate the
impact of the pandemic; Alnylam's ability to discover and develop
novel drug candidates and delivery approaches and successfully
demonstrate the efficacy and safety of its product candidates; the
pre-clinical and clinical results for its product candidates;
actions or advice of regulatory agencies and Alnylam’s ability to
obtain and maintain regulatory approval for its product candidates,
as well as favorable pricing and reimbursement; successfully
launching, marketing and selling its approved products globally;
delays, interruptions or failures in the manufacture and supply of
its product candidates or its marketed products; obtaining,
maintaining and protecting intellectual property; Alnylam’s ability
to successfully expand the indication for ONPATTRO (or vutrisiran,
if approved) in the future; Alnylam's ability to manage its growth
and operating expenses through disciplined investment in operations
and its ability to achieve a self-sustainable financial profile in
the future without the need for future equity financing; Alnylam’s
ability to maintain strategic business collaborations; Alnylam's
dependence on third parties for the development and
commercialization of certain products, including Novartis,
Regeneron and Vir; the outcome of litigation; the risk of
government investigations; and unexpected expenditures; as well as
those risks more fully discussed in the “Risk Factors” filed with
Alnylam's most recent Quarterly Report on Form 10-Q filed with the
Securities and Exchange Commission (SEC) and in its other SEC
filings. In addition, any forward-looking statements represent
Alnylam's views only as of today and should not be relied upon as
representing its views as of any subsequent date. Alnylam
explicitly disclaims any obligation, except to the extent required
by law, to update any forward-looking statements.
This release is not intended to convey conclusions about
efficacy or safety as to any investigational uses or dosing
regimens of any investigational RNAi therapeutics. There is no
guarantee that any investigational therapeutics or dosing regimens
for such therapeutics will successfully complete clinical
development or gain health authority approval.
__________________________________ i Hypertension. World Health
Organization.
https://www.who.int/news-room/fact-sheets/detail/hypertension.
Published September 2019. Accessed June 2021. ii Carey, R. M.,
Muntner, P., Bosworth, H. B., & Whelton, P. K. (2018).
Prevention and Control of Hypertension: JACC Health Promotion
Series. Journal of the American College of Cardiology, 72(11),
1278–1293. https://doi.org/10.1016/j.jacc.2018.07.008
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version on businesswire.com: https://www.businesswire.com/news/home/20210630005138/en/
Alnylam Pharmaceuticals, Inc. Christine Regan Lindenboom
(Investors and Media)
+1 617-682-4340
Joshua Brodsky
(Investors) +1 617-551-8276
Alnylam Pharmaceuticals (NASDAQ:ALNY)
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