– Single Doses of ALN-APP Achieve Sustained
Pharmacodynamic Activity up to 10 Months After Administration –
– Observed Marked Reductions in Aβ42 and Aβ40,
Amyloid Fragments Implicated in Alzheimer’s Disease and Cerebral
Amyloid Angiopathy –
– First Patient Dosed in Multiple-dose Part B
Portion of Study, with the Study Proceeding in Canada, UK, and the
Netherlands –
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) today announced
additional positive interim results for the ongoing single
ascending dose portion of the Phase 1 study of ALN-APP, an
investigational RNAi therapeutic targeting amyloid precursor
protein (APP) in development for the treatment of Alzheimer’s
disease and cerebral amyloid angiopathy (CAA). The data were
presented today in a late-breaker session at the 16th Clinical
Trials on Alzheimer’s Disease (CTAD) conference, being held October
24-27, 2023, in Boston, MA. ALN-APP is the first clinical-stage
program using Alnylam's proprietary C16-siRNA conjugate platform
for central nervous system (CNS) delivery and the first
investigational RNAi therapeutic to demonstrate gene silencing in
the human brain. ALN-APP is being developed in collaboration with
Regeneron.
“Today’s results showcase the exciting emerging profile of
ALN-APP. This novel approach appears generally well-tolerated and
is able to target the amyloid pathway successfully, robustly
lowering target engagement biomarkers sAPPα and sAPPβ and
maintaining a significant effect up to 10 months after
administration,” said Dr. Cath Mummery, Consultant Neurologist and
Head of Clinical Trials, Dementia Research Centre, University
College London. “For the first time, we also see that single doses
of ALN-APP can reduce cerebral spinal fluid levels of Aβ42 and
Aβ40, which are the amyloidogenic peptides that are the primary
components of amyloid deposits in Alzheimer’s disease and CAA. This
approach warrants further study to evaluate whether it can
potentially interrupt relentless progression of these two
devastating diseases.”
Twenty patients have been enrolled in three single-dose cohorts
in Part A of the ongoing Phase 1 study in patients with early-onset
Alzheimer’s disease. In this study to date, blinded single doses of
ALN-APP, which are administered by intrathecal injection, have been
well tolerated. All adverse events were mild or moderate in
severity. Cerebral spinal fluid (CSF) safety biomarkers, routine
labs, and the exploratory biomarker neurofilament light chain (NfL)
all continue to show no concerning trends. Patients treated with a
single dose of 75mg ALN-APP experienced rapid and sustained
reduction in CSF of both soluble APPα (sAPPα) and soluble APPβ
(sAPPβ), biomarkers of target engagement, with maximum reductions
of 84% and 90%, respectively. These effects were highly durable,
with mean reductions in sAPPα and sAPPβ of 33% and 39%,
respectively, at 10 months after a single 75mg dose. Available data
on exploratory disease-related biomarkers showed robust reductions
in CSF of Aβ42 and Aβ40, the soluble forms of the amyloidogenic
peptides that aggregate into amyloid deposits in AD and CAA. At two
months after a single dose of 75mg ALN-APP, mean reductions in CSF
Aβ42 and Aβ40 were 49% and 71%, respectively.
Further exploration of single doses of ALN-APP is ongoing in
Part A. In addition, the first patient has now been dosed in Part
B, the multiple-dose part of the study. Part B was previously
initiated in Canada and has also now received all required
approvals to proceed in the UK and the Netherlands. The multiple
dose part of the study remains on partial clinical hold in the U.S.
due to findings observed in non-clinical chronic toxicology
studies.
“These additional interim data further illustrate the potential
for RNAi therapeutics to set a new standard for silencing
disease-causing genes in the CNS, providing evidence that a single
dose of ALN-APP can achieve deep target engagement, a long duration
of action, and an encouraging early safety profile,” said Tim
Mooney, Director, ALN-APP Program Leader at Alnylam. “The robust
lowering we see in Aβ42 and Aβ40 shows that reducing APP protein
production with RNAi can reduce these downstream disease-associated
peptides and gives us confidence as we proceed with Part B of the
Phase 1 study and further explore the opportunity for ALN-APP in
both Alzheimer’s disease and CAA.”
Successful human translation of the C16-siRNA conjugate platform
is unlocking a broader portfolio of CNS programs. In addition to
ALN-APP, Alnylam and Regeneron have named 10 targets in the CNS as
part of their exclusive collaboration established in 2019 to
discover RNAi therapeutics for CNS and ocular diseases.
About the Phase 1 Study of ALN-APP The Phase 1 study is a
multicenter, randomized, double-blind, placebo-controlled trial
designed to evaluate the safety, tolerability, pharmacokinetic, and
pharmacodynamic effects of ALN-APP in patients with early-onset
Alzheimer’s disease (EOAD). The study is being conducted in two
parts: single ascending dose phase (Part A) and multiple dose phase
(Part B) in patients with EOAD. The planned enrollment for this
study is up to 60 patients.
The interim readout of the Phase 1 study of ALN-APP is focused
on assessing safety, tolerability and levels of target engagement
biomarkers, sAPPα and sAPPβ.
About ALN-APP ALN-APP is an investigational,
intrathecally administered RNAi therapeutic targeting amyloid
precursor protein (APP) in development for the treatment of
Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA).
Genetic mutations that increase production of APP or alter its
cleavage cause early-onset AD, early-onset CAA, or both. ALN-APP is
designed to decrease APP mRNA in the central nervous system (CNS),
to decrease synthesis of APP protein and all downstream
intracellular and extracellular APP-derived cleavage products,
including amyloid beta (Aβ). Reducing APP protein production is
expected to reduce the secretion of Aβ peptides that aggregate into
extracellular amyloid deposits and reduce the intraneuronal APP
cleavage products that trigger the formation of neurofibrillary
tangles and cause neuronal dysfunction in Alzheimer’s disease.
ALN-APP is the first program utilizing Alnylam’s proprietary
C16-siRNA conjugate technology, which enables enhanced delivery to
cells in the CNS. This program is being developed in collaboration
with Regeneron Pharmaceuticals. The safety and efficacy of ALN-APP
have not been evaluated by the FDA, EMA, or any other health
authority.
About Alzheimer’s Disease Alzheimer’s disease (AD) is the
most common neurodegenerative disease and the most common form of
dementia, affecting over 30 million people worldwide. AD is
characterized by progressive memory loss and cognitive decline,
with neuropathological accumulation of amyloid plaques,
neurofibrillary tangles, and neuroinflammation, ultimately
resulting in significant brain atrophy. Disease progression results
in progressive loss of independence, increased caregiver burden,
institutionalization, and premature death. Early-onset Alzheimer’s
disease (EOAD) refers to a subgroup of AD with symptom onset prior
to the age of 65, representing approximately 4% to 6% of all AD.
EOAD is the leading cause of dementia in younger individuals and is
a significant cause of disability and early mortality. Available
treatment options include symptomatic treatment and treatment to
reduce amyloid deposits in the brain. There are currently no
available treatments that have been shown to halt or reverse the
progression of the disease.
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 or disease pathway 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 Pharmaceuticals
(Nasdaq: ALNY) has led 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 and prevalent
diseases with unmet need. Based on Nobel Prize-winning science,
RNAi therapeutics represent a powerful, clinically validated
approach yielding transformative medicines. Since its founding in
2002, Alnylam has led the RNAi Revolution and continues to deliver
on a bold vision to turn scientific possibility into reality.
Alnylam’s commercial RNAi therapeutic products are ONPATTRO®
(patisiran), AMVUTTRA® (vutrisiran), GIVLAARI® (givosiran), OXLUMO®
(lumasiran), and Leqvio® (inclisiran), which is being developed and
commercialized by Alnylam’s partner, Novartis. Alnylam has a deep
pipeline of investigational medicines, including multiple 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 X (formerly Twitter) at @Alnylam, on LinkedIn, or
on Instagram.
Alnylam Forward Looking Statements This press release
contains forward-looking statements within the meaning of Section
27A of the Securities Act of 1933 and Section 21E of the Securities
Exchange Act of 1934. All statements other than historical
statements of fact regarding Alnylam’s expectations, beliefs,
goals, plans or prospects including, without limitation,
expectations regarding Alnylam’s aspiration to become a leading
biotech company and the planned achievement of its “Alnylam P5x25”
strategy, the potential for Alnylam to identify new potential drug
development candidates and advance its research and development
programs, including ALN-APP, Alnylam’s ability to obtain approval
for new commercial products or additional indications for its
existing products, and Alnylam’s projected commercial and financial
performance, should be considered forward-looking statements.
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; Alnylam’s
ability to successfully execute on its “Alnylam P5x25” strategy;
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 Alnylam’s product candidates, including vutrisiran;
actions or advice of regulatory agencies and Alnylam’s ability to
obtain and maintain regulatory approval for its product candidates,
including vutrisiran, as well as favorable pricing and
reimbursement; successfully launching, marketing and selling
Alnylam’s approved products globally; delays, interruptions or
failures in the manufacture and supply of Alnylam’s product
candidates or its marketed products; delays or interruptions in the
supply of resources needed to advance Alnylam’s research and
development programs, including as may arise from recent
disruptions in the supply of non-human primates; obtaining,
maintaining and protecting intellectual property; Alnylam’s ability
to successfully expand the indication AMVUTTRA 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 Roche, Novartis, Sanofi, Regeneron and Vir; the
outcome of litigation; the risks of future government
investigations; and unexpected expenditures; as well as those risks
more fully discussed in the “Risk Factors” filed with Alnylam's
2022 Annual Report on Form 10-K filed with the Securities and
Exchange Commission (SEC), as may be updated from time to time in
Alnylam’s subsequent Quarterly Reports on Form 10-Q 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 press release discusses investigational RNAi therapeutics
and is not intended to convey conclusions about efficacy or safety
as to those investigational therapeutics. There is no guarantee
that any investigational therapeutics will successfully complete
clinical development or gain health authority approval.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231025380274/en/
Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenboom (Investors and Media)
+1-617-682-4340
Josh Brodsky (Investors) +1-617-551-8276
Alnylam Pharmaceuticals (NASDAQ:ALNY)
Historical Stock Chart
From Apr 2024 to May 2024
Alnylam Pharmaceuticals (NASDAQ:ALNY)
Historical Stock Chart
From May 2023 to May 2024