− Single Dose of Nucresiran 300mg or Higher Led
to Rapid Knockdown of Mean TTR Levels of Greater than 90% by Day 15
that was Sustained at Six Months −
− At These Doses, Peak Reduction of Mean TTR
Levels of Greater than 96% were Achieved by Day 29 −
− Data Support Potential for Biannual or Annual
Subcutaneous Dosing, Representing a New Paradigm in the Treatment
of ATTR Amyloidosis −
− Encouraging Safety and Tolerability Observed
−
− Alnylam Continues to Expect to Share Phase 3
Development Plans in Q1 2025 –
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, today announced the presentation of new
results from its Phase 1 study of nucresiran (formerly
ALN-TTRsc04), a next-generation RNAi therapeutic in development for
the treatment of transthyretin (ATTR) amyloidosis. The data were
presented in an oral session at the American Heart Association
Scientific Sessions 2024 in Chicago.
These new results demonstrated that a single dose of nucresiran
at 300 mg or higher led to rapid knockdown of serum TTR with low
inter-patient variability, with mean reductions of greater than 90%
from baseline achieved at Day 15 and sustained through at least Day
180. At these doses, peak reduction of mean TTR levels of greater
than 96% were achieved by Day 29. Furthermore, serum TTR levels
remained substantially reduced at Day 360 with a mean reduction of
greater than 70% after a single 300 mg dose. Day 360 results are
not yet available for the 600 mg and 900 mg dose cohorts. All doses
of nucresiran have been well tolerated to date.
“We are very excited by these new Phase 1 data with nucresiran,
our next-generation TTR-targeting RNAi therapeutic, which
demonstrated that a single dose of ≥300 mg achieved rapid knockdown
of TTR greater than 90% from Day 15 that was sustained to at least
six months,” said Pushkal Garg, M.D., Chief Medical Officer,
Alnylam. “Furthermore, we are encouraged by the potential of
nucresiran to reduce interpatient variability in TTR lowering.
Nucresiran utilizes our IKARIA platform, which has now demonstrated
the potential to achieve durability supportive of biannual or
annual dosing, representing a potential new paradigm in the
treatment of ATTR amyloidosis. Importantly, nucresiran has been
well tolerated at all dose levels tested to date. We look forward
to sharing Phase 3 development plans in the first quarter of
2025.”
The ongoing Phase 1 dose-finding study evaluated the safety, as
well as pharmacodynamics and pharmacokinetics, of single doses of
nucresiran in healthy subjects. As previously presented at
Alnylam’s R&D Day in December 2023, a single dose of nucresiran
led to rapid knockdown of serum TTR that was highly durable.
In subjects receiving a single 300 mg dose of nucresiran, mean
serum TTR reduction of 90.3% was observed at Day 15, 96.5% at Day
29, and 92.6% at Day 180. At Day 360, mean serum TTR Reduction was
71.12%. In subjects receiving a single 600 mg dose, mean serum TTR
reduction of 95.0% was observed at Day 15, 97.8% at Day 29, and
96.0% at Day 180. In subjects receiving a single 900 mg dose, mean
serum TTR reduction of 91.7% was observed at Day 15, 96.7% at Day
29, and 94.2% at Day 180. As of the data cutoff date, TTR knockdown
levels at Day 360 were not available for either the 600 mg or 900
mg cohort.
There has been low inter-patient variability in the TTR
reduction observed; at Day 29, TTR reduction ranged from 96.0 –
96.7% in the 300 mg cohort, 96.6 – 98.6% in the 600 mg cohort, and
96.0 - 97.3% in the 900 mg cohort.
In the study, nucresiran has been well tolerated at all tested
doses. The majority of adverse events across doses have been mild
and none have been considered to be related to treatment. There
have been no injection site reactions and no safety signals
identified, including no liver-related signals.
Phase 1 Study Design
The Phase 1 trial is a randomized, double-blind,
placebo-controlled, single ascending dose study designed to
evaluate the safety, tolerability, pharmacokinetic (PK) and
pharmacodynamic (PD) effects of nucresiran in healthy adult
subjects. The study enrolled 48 healthy adult subjects randomized
3:1 to receive a single ascending dose of 5, 25, 100, 300, 600, or
900 mg of nucresiran or placebo. The primary endpoint of the study
is safety and secondary endpoints include the change from baseline
in serum TTR over time, as well as characterization of plasma and
urine pharmacokinetics (PK) of nucresiran.
About Nucresiran
Nucresiran is an investigational RNAi therapeutic in development
to deliver rapid knockdown of mutant and wild-type transthyretin
(TTR) and address the underlying cause of transthyretin (ATTR)
amyloidosis. As part of Alnylam’s proprietary IKARIA™ platform,
nucresiran has the potential to achieve deeper and more durable
rapid knockdown of TTR, allowing for less frequent dosing. The
safety and efficacy of nucresiran have not been established or
evaluated by the FDA, EMA or any other health authority.
About ATTR
Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly
progressive, debilitating and fatal disease caused by misfolded
transthyretin (TTR) proteins, which accumulate as amyloid deposits
in various parts of the body, including the nerves, heart and
gastrointestinal tract. Patients may present with polyneuropathy,
cardiomyopathy or both manifestations of disease. There are two
different forms of ATTR – hereditary ATTR (hATTR), which is caused
by a TTR gene variant and affects approximately 50,000 people
worldwide, and wild-type ATTR (wtATTR), which occurs without a TTR
gene variant and impacts an estimated 200,000-300,000 people
worldwide.
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 (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 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, or on LinkedIn,
Facebook, or 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, the potential for nucresiran to achieve durability
supportive of biannual or annual dosing and to represent a new
paradigm in the treatment of ATTR amyloidosis; the potential to
reduce interpatient variability in TTR lowering with nucresiran;
and the timing of Alnylam’s release of Phase 3 development plans
for nucresiran 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, risks and uncertainties relating to:
Alnylam’s ability to successfully execute on its “Alnylam P5x25”
strategy; Alnylam’s ability to successfully demonstrate the
efficacy and safety of its product candidates; the pre-clinical and
clinical results for Alnylam’s product candidates; actions or
advice of regulatory agencies and Alnylam’s ability to obtain
regulatory approval for its product candidates, as well as
favorable pricing and reimbursement; successfully launching,
marketing and selling Alnylam’s approved products globally; and any
delays, interruptions or failures in the manufacture and supply of
Alnylam’s product candidates or its marketed products; as well as
those risks more fully discussed in the “Risk Factors” filed with
Alnylam’s 2023 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20241117936734/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)
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