− Initiates Clinical Study of Biannual Dosing
Regimen of Investigational Vutrisiran in hATTR Patients with
Polyneuropathy, with Data Expected in 2022 Potentially Supporting
sNDA Submission –
− Introduces New ATTR Program Aimed at
Achieving Annual Dosing Regimen with Highly Potent and Reversible
Effects; Expected IND Filing at or Around Year-end 2022 –
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, today announced that it has started a
clinical study of a biannual dosing regimen of vutrisiran, an
investigational RNAi therapeutic in development for the treatment
of transthyretin-mediated (ATTR) amyloidosis. The study is being
conducted during a randomized treatment extension (RTE) period in
the HELIOS-A Phase 3 study, and will characterize the safety,
efficacy, and TTR reduction of a 50 mg biannual dosing regimen of
subcutaneously administered vutrisiran in patients with hereditary
ATTR (hATTR) amyloidosis with polyneuropathy. In addition, the
Company announces today advancement of a new pre-clinical ATTR
amyloidosis program aimed at achieving highly potent and reversible
TTR reduction of over 90 percent with an annual subcutaneous dosing
regimen.
“Alnylam has a long-standing commitment to continuous innovation
aimed at providing breakthrough treatment options for patients with
ATTR amyloidosis. We’re pleased to have now initiated a clinical
study of a biannual dosing regimen for vutrisiran. If shown to be
safe and efficacious, the new dosing regimen may provide some
patients with a treatment option that neatly aligns the frequency
of administration with biannual visits to their doctor,” said Rena
Denoncourt, Vice President, Vutrisiran Program Leader. “In
addition, based on continued discoveries from our RNAi therapeutics
platform, we’re also advancing a new pre-clinical program that
could enable highly potent and reversible TTR reduction with an
annual dosing regimen. We believe that once yearly dosing could
provide a vaccine-like dosing schedule strategy for management of
ATTR amyloidosis, providing meaningful life-cycle management for
our ATTR franchise.”
As reported previously, positive results were achieved in
HELIOS-A with a 25 mg quarterly dosing regimen of subcutaneously
administered vutrisiran; a New Drug Application (NDA) for the
approval of vutrisiran was filed with the U.S. Food and Drug
Administration (FDA) in April 2021 for the treatment of the
polyneuropathy of hATTR amyloidosis in adults1. The vutrisiran
biannual dosing study is being conducted as part of the HELIOS-A
randomized, open-label study. During the RTE period, which begins
following completion of the 18-month HELIOS-A treatment period,
patients are randomized 1:1 to receive 25 mg of vutrisiran
quarterly or 50 mg of vutrisiran biannually for the remainder of
the study. Patients will undergo periodic assessments for safety
and TTR reduction, and efficacy assessments at months nine and 18
of the RTE. As previously disclosed in mid-2020, clinical
pharmacology data indicate that a 50 mg biannual dose of vutrisiran
is expected to achieve comparable TTR reduction – over 80 percent –
to that demonstrated with the 25 mg quarterly dosing regimen of
vutrisiran. Alnylam expects results from the RTE study in 2022; if
positive, data would support a supplemental NDA (sNDA) submission
to the FDA.
The new ATTR program announced today stems from continued
innovation from Alnylam’s RNAi therapeutics platform efforts.
Specifically, Alnylam scientists have developed an extended
duration platform, called IKARIA™, that is aimed at highly potent
(>90 percent) target mRNA silencing with an annual dosing
regimen. Targeting mRNA with the IKARIA platform is expected to
yield small interfering RNA (siRNA) with potentially long-acting
and reversible effects and a proven RNAi mechanism of action. This
new platform has yielded ALN-TTRsc04, which is planned to enter
clinical development at or around year-end 2022 with an
investigational new drug (IND) application filing. If successfully
developed, ALN-TTRsc04 is expected to have minimal, if any,
third-party royalty obligations. Alnylam plans to present data from
its IKARIA platform and ALN-TTRsc04 program at a scientific meeting
in mid-2021.
“Our platform team continues to discover innovations for RNAi
therapeutics that we believe can deliver meaningful advances for
patients. Our new IKARIA platform represents an excellent example,”
said Kevin Fitzgerald, Ph.D., Senior Vice President, Chief
Scientific Officer. “With IKARIA, we are confident we can design
long-acting siRNA with all the proven pharmacological advantages
and established human experience of RNAi therapeutics, including
predictable dose-dependence and onset/offset kinetics, without
permanent effects on the target or cell.”
About HELIOS-A Phase 3 Study
HELIOS-A (NCT03759379) is a Phase 3 global, randomized,
open-label study to evaluate the efficacy and safety of vutrisiran.
The study enrolled 164 patients with hATTR amyloidosis with
polyneuropathy at 57 sites in 22 countries. Patients were
randomized 3:1 to receive either 25mg of vutrisiran (N=122) via
subcutaneous injection once every three months or 0.3 mg/kg of
patisiran (N=42) via intravenous infusion once every three weeks
(as a reference comparator) for 18 months. The primary endpoint is
the change from baseline in mNIS+7 score at nine months, relative
to an external placebo group (APOLLO). Secondary endpoints at 9
months are the change from baseline in the Norfolk QoL-DN score and
the timed 10-MWT, relative to an external placebo group. Changes
from baseline in NT-proBNP were evaluated as an exploratory
endpoint at nine months. The efficacy results of vutrisiran in
HELIOS-A are compared to the placebo group from the landmark APOLLO
Phase 3 study, which evaluated the efficacy and safety of patisiran
in a patient population similar to that studied in HELIOS-A.
Additional secondary endpoints at 18 months will be evaluated in
the HELIOS-A study, including change from baseline in mNIS+7,
Norfolk QoL-DN, 10-MWT, modified body mass index (mBMI),
Rasch-built Overall Disability Scale (R-ODS), and serum
transthyretin (TTR) levels. Additional exploratory cardiac endpoint
data at the 18-month time point will be evaluated, including
NT-proBNP, echocardiographic measures and cardiac amyloid
assessments with technetium scintigraphy imaging. Following the
18-month treatment period, all patients are eligible to receive
vutrisiran for an additional 18 months as part of the randomized
treatment extension.
About Vutrisiran
Vutrisiran is an investigational, subcutaneously administered
RNAi therapeutic in development for the treatment of ATTR
amyloidosis, which encompasses both hereditary (hATTR) and
wild-type (wtATTR) amyloidosis. It is designed to target and
silence specific messenger RNA, blocking the production of
wild-type and variant transthyretin (TTR) protein before it is
made. Quarterly administration of vutrisiran may help to reduce
deposition and facilitate the clearance of TTR amyloid deposits in
tissues and potentially restore function to these tissues.
Vutrisiran utilizes Alnylam’s Enhanced Stabilization Chemistry
(ESC)-GalNAc-conjugate delivery platform, designed for increased
potency and high metabolic stability that may allow for infrequent
subcutaneous injections. The safety and efficacy of vutrisiran have
not been evaluated by the U.S. Food and Drug Administration,
European Medicines Agency or any other health authority.
About hATTR Amyloidosis
Hereditary transthyretin (TTR)-mediated amyloidosis (hATTR) is
an inherited, progressively debilitating, and fatal disease caused
by variants (i.e., mutations) in the TTR gene. TTR protein is
primarily produced in the liver and is normally a carrier of
vitamin A. Variants in the TTR gene cause abnormal amyloid proteins
to accumulate and damage body organs and tissue, such as the
peripheral nerves and heart, resulting in intractable peripheral
sensory-motor neuropathy, autonomic neuropathy, and/or
cardiomyopathy, as well as other disease manifestations. hATTR
amyloidosis, represents a major unmet medical need with significant
morbidity and mortality affecting approximately 50,000 people
worldwide. The median survival is 4.7 years following diagnosis,
with a reduced survival (3.4 years) for patients presenting with
cardiomyopathy.
About IKARIA™ Platform
Alnylam’s IKARIA platform takes advantage of more than two
decades of experience in developing RNAi therapeutics. IKARIA
enables an extended duration of activity in preclinical studies,
with potential for annual dosing in humans, and has design features
which provide exquisite specificity, further widening the potential
therapeutic index, with enhanced target reduction levels.
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 vutrisiran and its potential as a low-dose, once
quarterly, subcutaneously administered treatment option with an
encouraging safety profile for patients with hATTR amyloidosis with
polyneuropathy, the potential of a new biannual dosing regimen of
vutrisiran for such patients, the expected timing of additional
data on the biannual dosing regimen and potential additional
regulatory filings for vutrisiran, including an sNDA with the FDA,
if the data for such biannual dosing are positive, the potential of
the IKARIA platform to enable highly potent (>90 percent) target
mRNA silencing with an annual dosing regimen and the expected
timing for the initiation of clinical studies for ALN-TTRsc04, that
could enable highly potent and reversible TTR reduction with an
annual dosing regimen and, if successful, could provide a
vaccine-like strategy for management of ATTR amyloidosis, becoming
a leading biotech company, and the achievement of its “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.
1 The safety and efficacy of investigational vutrisiran have not
been evaluated by the U.S. Food and Drug Administration, European
Medicines Agency, or any other health authority. Regulatory
authorities have not yet determined that vutrisiran is safe or
effective for any indication.
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version on businesswire.com: https://www.businesswire.com/news/home/20210511005574/en/
Alnylam Pharmaceuticals, Inc. Christine Regan Lindenboom
(Investors and Media)
617-682-4340 Josh Brodsky
(Investors) 617-551-8276
Alnylam Pharmaceuticals (NASDAQ:ALNY)
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