– Company Announces Potential for a Biannual
Dosing Regimen Option for its Investigational RNAi Therapeutic
Vutrisiran, Providing Support for Further Product Differentiation
as a Potential Best-in-Class Agent –
– New Clinical Data Presented at the European
Society of Cardiology 2020 Congress Provide Further Evidence that
Treatment with Patisiran may Lead to Substantial Reduction in
Cardiac Amyloid Burden in ATTR Amyloidosis –
– Company Remains on Track to Report Topline
Results from HELIOS-A in Early 2021 and to Complete Enrollment in
APOLLO-B in 2021; HELIOS-B Enrollment Expanding Globally –
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, will host an “RNAi Roundtable” webinar today
at 12:00 p.m. ET, which will focus on progress across its ATTR
amyloidosis programs. The Company will discuss the potential for a
biannual subcutaneous dosing regimen for vutrisiran, as well as
discuss ongoing Phase 3 development for patisiran and vutrisiran
across the APOLLO-B, HELIOS-A, and HELIOS-B studies. The Company
also announced data from a clinical study evaluating the impact of
patisiran and diflunisal, a TTR stabilizer, on cardiac amyloid
burden. These data, presented at the European Society of Cardiology
(ESC) 2020 Congress, suggest that treatment with patisiran may lead
to cardiac amyloid regression in patients with cardiomyopathy
associated with ATTR amyloidosis.
“We believe we have the potential to build an industry-leading
franchise of medicines for the treatment of ATTR amyloidosis, and
we look forward to highlighting our progress in our RNAi Roundtable
later today. Amongst other achievements, we will discuss the
opportunity for a biannual dosing regimen option for vutrisiran
providing further differentiation to achieve a potential
best-in-class profile. In addition, we will update on ongoing
progress for our TTR programs in our APOLLO-B, HELIOS-A, and
HELIOS-B Phase 3 studies of patisiran and vutrisiran,” said Eric
Green, Senior Vice President and General Manager of the TTR
Program. “Moreover, we will summarize new recently presented data
supporting the potential for patisiran to achieve a substantial
reduction in cardiac amyloid burden in ATTR amyloidosis, with
associated functional and biomarker improvements. We remain
committed to developing additional therapeutic options for the
treatment of ATTR amyloidosis and driving innovation that can
potentially help improve patient outcomes and treatment
experience.”
Vutrisiran Clinical Development Program
Vutrisiran, an investigational RNAi therapeutic in development
for the treatment of ATTR amyloidosis, is currently being evaluated
in the HELIOS Phase 3 program. HELIOS-A is a randomized,
open-label, global multi-center study evaluating the efficacy and
safety of vutrisiran in patients with hATTR amyloidosis with
polyneuropathy; this study is fully enrolled. The Company
reiterates that topline results from HELIOS-A are expected to be
announced in early 2021. In this study, patients receive 25mg of
vutrisiran subcutaneously once every 12 weeks.
Alnylam announces today that it has obtained clinical
pharmacology data supporting the potential for a biannual
subcutaneous dosing regimen for vutrisiran. Specifically, new
analyses show that a biannual 50mg dosing regimen is expected to
achieve comparable TTR knockdown to results with a 25mg quarterly
dosing regimen and to a once every three weekly intravenous dosing
regimen employed with patisiran. A biannual dosing regimen option
for vutrisiran is expected to support further product
differentiation for a potential best-in-class profile, and the
Company plans to work with regulatory authorities in late 2020 to
determine the most efficient regulatory path forward.
The Company affirmed that enrollment continues in the HELIOS-B
Phase 3 study, a randomized, double-blind, placebo-controlled,
global multi-center study evaluating the efficacy and safety of
vutrisiran in patients with ATTR amyloidosis with cardiomyopathy.
In this study, patients receive 25mg of vutrisiran subcutaneously
or placebo once every 12 weeks, and the primary endpoint is
mortality and CV hospitalization at 30 months with a planned
interim analysis. Alnylam has implemented steps to accelerate
enrollment in HELIOS-B to make up for slowed patient accrual during
the COVID-19 pandemic.
In April 2020, Alnylam announced that the U.S. Food and Drug
Administration (FDA) granted Fast Track designation to vutrisiran
for the treatment of the polyneuropathy of hereditary ATTR (hATTR)
amyloidosis.
Patisiran Clinical Development Program
Patisiran is being investigated for the treatment of ATTR
amyloidosis with cardiomyopathy in the APOLLO-B study. APOLLO-B is
a Phase 3, randomized, double-blind, placebo-controlled, global
multi-center study designed to evaluate the efficacy and safety of
patisiran in patients with ATTR amyloidosis with cardiomyopathy.
Enrollment in APOLLO-B continues, and the study enrollment is
expected to be completed in 2021.
Of interest, a study of 32 patients with hATTR cardiac
amyloidosis – presented at ESC 2020 held virtually August 29 -
September 1, 2020 – provides encouraging evidence of the potential
for substantial reduction in cardiac amyloid burden in patients
treated with patisiran. The non-randomized study, led by the
University College Hospital in the UK, was conducted to evaluate
the impact of patisiran and diflunisal, a TTR stabilizer, on
cardiac amyloid load as measured by cardiac magnetic resonance
(CMR) and T1 mapping, in patients with hATTR amyloidosis. Patients
were assessed with echocardiogram, CMR, NT-proBNP, and 6-minute
walk test (6MWT) at baseline and at one year. At the one-year time
point, there was a substantial reduction in cardiac amyloid burden
in 45% of patients who received patisiran (N=16). Patients treated
with patisiran also showed a reduction in extracellular volume
fraction (ECV) compared to an increase in ECV in the control group
(n=16). These findings show the potential for CMR to be used to
track response in treated patients with ATTR cardiac amyloidosis.
Patients treated with patisiran also showed an improvement in
change in 6MWT at one year, compared to patients in the control
group. According to the authors, combination therapy with an RNAi
therapeutic against transthyretin and a TTR stabilizing agent may
be synergistic given enhanced stoichiometry of TTR stabilizers in
the face of markedly reduced plasma transthyretin
concentration.
Today’s RNAi Roundtable webinar can be accessed at
www.alnylam.com/events or on the Capella section of the Alnylam
website.
About ONPATTRO® (patisiran)
ONPATTRO is an RNAi therapeutic that was approved in the United
States and Canada for the treatment of the polyneuropathy of hATTR
amyloidosis in adults. ONPATTRO is also approved in the European
Union, Switzerland and Brazil for the treatment of hATTR
amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and
in Japan for the treatment of hATTR amyloidosis with
polyneuropathy. ONPATTRO is an intravenously administered RNAi
therapeutic targeting transthyretin (TTR). It is designed to target
and silence TTR messenger RNA, thereby blocking the production of
TTR protein before it is made. ONPATTRO blocks the production of
TTR in the liver, reducing its accumulation in the body’s tissues
in order to halt or slow down the progression of the polyneuropathy
associated with the disease. For more information about ONPATTRO,
visit ONPATTRO.com.
ONPATTRO (patisiran) lipid complex injection Important
Safety Information
Infusion-Related Reactions
Infusion-related reactions (IRRs) have been observed in patients
treated with ONPATTRO. In a controlled clinical study, 19 percent
of ONPATTRO-treated patients experienced IRRs, compared to 9
percent of placebo-treated patients. The most common symptoms of
IRRs with ONPATTRO were flushing, back pain, nausea, abdominal
pain, dyspnea, and headache.
To reduce the risk of IRRs, patients should receive
premedication with a corticosteroid, acetaminophen, and
antihistamines (H1 and H2 blockers) at least 60 minutes prior to
ONPATTRO infusion. Monitor patients during the infusion for signs
and symptoms of IRRs. If an IRR occurs, consider slowing or
interrupting the infusion and instituting medical management as
clinically indicated. If the infusion is interrupted, consider
resuming at a slower infusion rate only if symptoms have resolved.
In the case of a serious or life-threatening IRR, the infusion
should be discontinued and not resumed.
Reduced Serum Vitamin A Levels and
Recommended Supplementation
ONPATTRO treatment leads to a decrease in serum vitamin A
levels. Supplementation at the recommended daily allowance (RDA) of
vitamin A is advised for patients taking ONPATTRO. Higher doses
than the RDA should not be given to try to achieve normal serum
vitamin A levels during treatment with ONPATTRO, as serum levels do
not reflect the total vitamin A in the body.
Patients should be referred to an ophthalmologist if they
develop ocular symptoms suggestive of vitamin A deficiency (e.g.
night blindness).
Adverse Reactions
The most common adverse reactions that occurred in patients
treated with ONPATTRO were upper respiratory-tract infections (29
percent) and infusion-related reactions (19 percent).
For additional information about ONPATTRO, please see the full
Prescribing Information.
About hATTR Amyloidosis
Hereditary transthyretin (TTR)-mediated amyloidosis (hATTR) is
an inherited, progressively debilitating, and often fatal disease
caused by mutations in the TTR gene. TTR protein is primarily
produced in the liver and is normally a carrier of vitamin A.
Mutations 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 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, 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), approved in the
U.S., EU, Canada, Japan, Switzerland and Brazil, and GIVLAARI®
(givosiran), approved in the U.S., EU, and Brazil. Alnylam has a
deep pipeline of investigational medicines, including six product
candidates that are in late-stage development. Alnylam is executing
on its “Alnylam 2020” strategy of building a multi-product,
commercial-stage biopharmaceutical company with a sustainable
pipeline of RNAi-based medicines to address the needs of patients
who have limited or inadequate treatment options. 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 or on LinkedIn.
Alnylam Forward Looking Statements
Various statements in this release, including, without
limitation, Alnylam's views and plans with respect to the potential
for RNAi therapeutics, including patisiran and vutrisiran, as
monotherapies or in combination with a TTR stabilizing agent,
Alnylam’s prospects for building an industry-leading ATTR
amyloidosis franchise, expected timing for completing the ongoing
APOLLO B Phase 3 study and completing enrollment and availability
of results in the ongoing HELIOS Phase 3 program, and expectations
regarding the achievement of its “Alnylam 2020” guidance for the
advancement and commercialization of RNAi therapeutics, 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 a future pandemic, such as the scope
and duration of the outbreak, government actions and restrictive
measures implemented in response, material delays in diagnoses of
rare diseases, initiation or continuation of treatment for diseases
addressed by Alnylam products, or in patient enrollment in clinical
trials, potential supply chain disruptions, and other potential
impacts to Alnylam’s business, the effectiveness or timeliness of
steps taken by Alnylam to mitigate the impact of the pandemic, and
Alnylam’s ability to execute business continuity plans to address
disruptions caused by the COVID-19 or a future 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, including patisiran and vutrisiran; the
pre-clinical and clinical results for its product candidates, which
may not be replicated or continue to occur in other subjects or in
additional studies or otherwise support further development of
product candidates for a specified indication or at all; actions or
advice of regulatory agencies, which may affect the design,
initiation, timing, continuation and/or progress of clinical trials
or result in the need for additional pre-clinical and/or clinical
testing; delays, interruptions or failures in the manufacture and
supply of its product candidates or its marketed products,
including ONPATTRO, GIVLAARI, inclisiran, lumasiran and vutrisiran;
obtaining, maintaining and protecting intellectual property;
intellectual property matters including potential patent litigation
relating to its platform, products or product candidates; obtaining
regulatory approval for its product candidates, including lumasiran
and inclisiran, and maintaining regulatory approval and obtaining
pricing and reimbursement for its products, including ONPATTRO and
GIVLAARI; progress in continuing to establish a commercial and
ex-United States infrastructure; successfully launching, marketing
and selling its approved products globally, including ONPATTRO and
GIVLAARI and achieving net product revenues for ONPATTRO within its
revised expected range during 2020; Alnylam’s ability to
successfully expand the indication for ONPATTRO in the future;
competition from others using technology similar to Alnylam's and
others developing products for similar uses; Alnylam's ability to
manage its growth and operating expenses within the reduced ranges
of guidance provided by Alnylam through the implementation of
further discipline in operations to moderate spend and its ability
to achieve a self-sustainable financial profile in the future
without the need for future equity financing; Alnylam’s ability to
establish and maintain strategic business alliances and new
business initiatives ; Alnylam's dependence on third parties,
including Regeneron, for development, manufacture and distribution
of certain products, including eye and CNS products, Ironwood, for
assistance with the education about and promotion of GIVLAARI, and
Vir for the development of ALN-COV and other potential RNAi
therapeutics targeting SARS-CoV-2 and host factors for SARS-CoV-2;
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 other filings that Alnylam makes
with the SEC. 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20200903005260/en/
Alnylam Pharmaceuticals, Inc. Christine Regan Lindenboom
(Investors and Media) 617-682-4340 Josh Brodsky (Investors)
617-551-8276
Alnylam Pharmaceuticals (NASDAQ:ALNY)
Historical Stock Chart
From Mar 2024 to Apr 2024
Alnylam Pharmaceuticals (NASDAQ:ALNY)
Historical Stock Chart
From Apr 2023 to Apr 2024