– Vutrisiran Met All 18 Month Secondary
Endpoints, Including Statistically Significant Improvements in
Neuropathy Impairment, Quality of Life (QoL), Gait Speed,
Nutritional Status and Overall Disability, Relative to External
Placebo –
– Vutrisiran Continued to Demonstrate Halting
or Reversal of Polyneuropathy, with Improvements in Neuropathy
Impairment and QoL Relative to Baseline –
– Exploratory Cardiac Data, Including Reduced
Technetium Uptake Relative to Baseline in Majority of Assessable
Patients, Continue to Support Potential for Vutrisiran to Reduce
Cardiac Amyloid Burden and Improve Cardiac Manifestations of
Disease –
– In Addition, Vutrisiran Continued to
Demonstrate Encouraging Safety and Tolerability Profile –
– Alnylam to Host Conference Call Today at 8:30
am ET –
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, announced today that the HELIOS-A Phase 3
study of vutrisiran, an investigational RNAi therapeutic in
development for the treatment of transthyretin-mediated (ATTR)
amyloidosis, met all secondary endpoints measured at 18 months in
patients with hATTR amyloidosis with polyneuropathy, including
statistically significant improvements in neuropathy impairment,
quality of life (QoL), gait speed, nutritional status and overall
disability, relative to placebo, and non-inferiority of serum TTR
reduction relative to the within-study patisiran arm. The results
were presented today in an oral session at the Société Francophone
du Nerf Périphérique (SFNP) Annual Meeting.
In HELIOS-A, patients treated with vutrisiran also showed
improvement in exploratory cardiac endpoints including NT-proBNP
and echocardiographic parameters relative to placebo, as well as
technetium uptake, relative to baseline, in a planned cohort of
patients. Vutrisiran also continued to demonstrate an encouraging
safety and tolerability profile consistent with the previously
reported Month 9 results. Alnylam previously announced that
HELIOS-A met its primary and secondary endpoints at 9 months and
study results were presented at the 2021 American Academy of
Neurology (AAN) Virtual Annual Meeting.
“These HELIOS-A results show that the improvement in neuropathy
impairment and quality of life observed with vutrisiran at 9 months
is maintained through Month 18, with the treatment effect
increasing over time and an encouraging safety profile. Further, we
are encouraged by the exploratory cardiac endpoint results,
particularly new data indicating that 18 months of vutrisiran
treatment resulted in reduced technetium uptake in the heart
compared to baseline in the majority of patients who were in a
planned cohort, suggesting the potential for amyloid regression. We
look forward to seeing data from the APOLLO-B and HELIOS-B studies,
which are investigating the potential of patisiran and vutrisiran,
respectively, to treat the cardiac manifestations of disease in
patients with ATTR amyloidosis with cardiomyopathy,” said Rena N.
Denoncourt, Vice President, TTR Franchise Lead. “Vutrisiran is
currently under review by multiple regulatory authorities around
the world, bringing us a step closer to potentially making this
low-dose, once-quarterly, subcutaneously administered treatment
option available for patients living with the polyneuropathy of
hATTR amyloidosis, and furthering our efforts to build an
industry-leading franchise of medicines for the treatment of ATTR
amyloidosis.”
HELIOS-A 18-Month Study Results At 18 months, vutrisiran
met all secondary endpoints in HELIOS-A, demonstrating
statistically significant improvement in clinical endpoints
compared to placebo and non-inferiority in serum TTR reduction
compared to the within-study patisiran arm, specifically:
- Vutrisiran treatment (N=122) resulted in a 0.46 point mean
decrease (improvement) in the modified Neuropathy Impairment Score
(mNIS+7) from baseline at 18 months as compared to a 28.09 point
mean increase (worsening) reported for the external placebo group
(N=77), resulting in a 28.55 point mean difference relative to
placebo (p equal to 6.5x10-20).
- Vutrisiran treatment also resulted in an mNIS+7 improvement
relative to baseline at 18 months in 48 percent of patients,
compared with 4 percent of patients who received placebo.
- Vutrisiran treatment resulted in a 1.2 point mean decrease
(improvement) in Norfolk QoL-DN score from baseline at 18 months as
compared to a 19.8 point mean increase (worsening) reported for the
external placebo group, resulting in a mean 21.0 point difference
relative to placebo (p equal to 1.8x10-10).
- Fifty-seven percent of patients treated with vutrisiran
experienced improvement in quality of life relative to baseline at
18 months, compared with 10 percent of patients who received
placebo.
- Vutrisiran achieved statistically significant improvement in
gait speed (10-MWT), nutritional status (mBMI), and disability
(R-ODS) at 18 months, compared with the external placebo group.
- Vutrisiran treatment resulted in a 0.024 meters/second mean
decrease in 10-MWT from baseline at 18 months as compared to a
0.264 meters/second mean decrease in the external placebo group,
resulting in a mean 0.239 meters/second increase relative to
placebo (p equal to 1.2x10-7).
- Vutrisiran treatment resulted in a 25.0 point mean increase
(improvement) in mBMI from baseline at 18 months as compared to a
115.7 point mean decrease in the external placebo group, resulting
in a 140.7 point mean increase relative to placebo (p equal to
4.2x10-15).
- Vutrisiran treatment resulted in a mean decrease of 1.5 points
from baseline in R-ODS at 18 months as compared to a 9.9 point mean
decrease in the external placebo group, resulting in an 8.4 point
mean increase relative to placebo (p equal to 3.5x10-15).
- As expected, non-inferiority of vutrisiran serum TTR reduction,
relative to the within-study patisiran reference comparator, was
established. Vutrisiran achieved a rapid and sustained reduction of
serum TTR at 18 months, with a mean reduction from baseline of 88
percent.
- Patients treated with vutrisiran also showed the potential for
improvement across exploratory cardiac endpoints.
- Compared to placebo, patients in the vutrisiran arm
demonstrated improvement in NT-proBNP, a biomarker of cardiac
stress, with an adjusted geometric fold change in the vutrisiran
patients of 0.94 and a change in placebo patients of 1.96 for a
nominal p-value of 9.6x10-10.
- Patients treated with vutrisiran also demonstrated a trend
towards improvement (nominal p values) in echocardiographic
parameters, relative to placebo including cardiac output (p=1.144
x10-5), LV end diastolic volume (p=4.021 x10-5), Global
longitudinal strain (p=0.3182) and mean LV wall thickness
(p=0.5228).
- In a planned cohort, vutrisiran also reduced cardiac uptake of
technetium on scintigraphy imaging, relative to baseline, providing
potential evidence of reduced amyloid burden in the heart. 68
percent of patients improved in technetium uptake as assessed by
normalized left ventricular total uptake and 65 percent of patients
demonstrated improvement in assessment of heart to contralateral
lung ratio. Furthermore, 28 percent showed a one grade or greater
improvement in the Perugini grading scale, with 68 percent of
patients maintaining a stable Perugini grade at Month 18, relative
to baseline.
Vutrisiran demonstrated an encouraging safety profile in
HELIOS-A at 18 months. There were three study discontinuations (2.5
percent) due to adverse events in the vutrisiran arm by Month 18,
one due to a non-fatal event of heart failure and two due to
deaths, neither of which was considered related to the study drug.
During the 18-month treatment period there were two serious adverse
events (SAEs) deemed related to vutrisiran by the study
investigator, consisting of dyslipidemia and urinary tract
infection. The two deaths and the two related SAEs were previously
reported at Month 9.
Treatment emergent adverse events (AEs) occurring in 10 percent
or more patients included fall, pain in extremity, diarrhea,
peripheral edema, urinary tract infection, arthralgia and
dizziness; with the exception of pain in extremity and arthralgia,
each of these events occurred at a similar or lower rate as
compared with external placebo. Injection site reactions (ISRs)
were reported in five patients (4.1 percent) and were all mild and
transient. There were no clinically significant changes in liver
function tests (LFTs).
To view the data presented by Alnylam at SFNP, please visit,
Capella
“The 18-month results of the HELIOS-A Phase 3 study build on the
results observed at 9 months and continue to underscore the
potential of vutrisiran as an attractive new treatment option that
can be administered subcutaneously four times a year,” said David
Adams, M.D., Ph.D., Department of Neurology, Bicetre hospital,
Greater Paris University Hospitals, AP-HP, University Paris Saclay
and Principal Investigator for the HELIOS-A trial. “The data
presented today are exciting, demonstrating additional progress
from ongoing research focused on meeting the needs of this diverse
group of patients living with a progressive, life-threatening,
multi-system disease, with a potential new option that may help
simplify their treatment.”
Filing and Review Status Vutrisiran is under review by
the U.S. Food and Drug Administration (FDA), the European Medicines
Agency (EMA), the Brazilian Health Regulatory Agency (ANVISA) and
the Japanese Pharmaceuticals and Medical Devices Agency (PMDA).
Vutrisiran has been granted Orphan Drug Designation in the U.S. and
the European Union (EU) for the treatment of ATTR amyloidosis.
Vutrisiran has also been granted a Fast Track designation in the
U.S. for the treatment of the polyneuropathy of hATTR amyloidosis
in adults. In the U.S., vutrisiran has received an action date
under the Prescription Drug User Fee Act (PDUFA) of April 14, 2022.
The Company received Orphan Drug Designation in Japan for
transthyretin type familial amyloidosis with polyneuropathy.
Conference Call Information Alnylam Management will
discuss the HELIOS-A 18-month results via a conference call on
Friday, January 21, 2022, at 8:30 am ET. To access the call, please
dial 877-312-7507 (domestic) or +1-631-813-4828 (international)
five minutes prior to the start time and refer to conference ID
2239918. A replay of the call will be available beginning at 11:30
am ET on the day of the call. To access the replay, please dial
855-859-2056 (domestic) or +1-404-537-3406 (international) and
refer to conference ID 2239918.
About hATTR Amyloidosis Hereditary transthyretin-mediated
(hATTR) amyloidosis 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 Vutrisiran Vutrisiran is an investigational,
subcutaneously administered RNAi therapeutic in development for the
treatment of ATTR amyloidosis, which encompasses both hATTR and
wild-type ATTR (wtATTR) amyloidosis. It is designed to target and
silence specific messenger RNA, potentially blocking the production
of wild-type and variant transthyretin (TTR) protein before it is
made. Quarterly, and potentially biannual, 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 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 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. The primary
endpoint is the change from baseline in mNIS+7 at 9 months.
Secondary endpoints at 9 months are the change from baseline in the
Norfolk QoL-DN score and the timed 10-MWT. Changes from baseline in
NT-proBNP were evaluated as an exploratory endpoint at 9 months.
Additional secondary endpoints at 18 months were 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 include 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 where they will receive
either 25mg vutrisiran once quarterly or 50mg vutrisiran once every
six months.
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 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) 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 20 years ago, 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),
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 the investigational
therapeutic vutrisiran and its potential as a low-dose, once
quarterly, subcutaneously administered treatment option with an
encouraging safety profile for patients living with the
polyneuropathy of hATTR amyloidosis, the potential for vutrisiran
to provide patients living with a progressive, life-threatening,
multi-system disease with a new option that may help simplify their
treatment, Alnylam’s progress in building an industry-leading
franchise of medicines for the treatment of ATTR amyloidosis, the
potential of vutrisiran to reduce technetium uptake in the heart
resulting in the potential for amyloid regression, the potential of
patisiran and vutrisiran to treat the cardiac manifestations of
disease in patients with ATTR amyloidosis with cardiomyopathy, the
ongoing regulatory review of vutrisiran around the world, including
the PDUFA date in the U.S., Alnylam’s aspiration to become a
leading biotech company, and the planned 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; the
potential impact of the recent leadership transition on Alnylam’s
ability to attract and retain talent and 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 its product
candidates, including vutrisiran and patisiran; 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 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 potential impact of a current government
investigation and the risk of future 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20220121005075/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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