ONPATTRO® is the Only
Treatment that Demonstrated Improvement, Relative to Baseline, in
both Polyneuropathy and Quality of Life Measures in Patients1,
2 with hATTR Amyloidosis
MISSISSAUGA, ON, July 23, 2019 /CNW/ - Alnylam
Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNA interference
(RNAi) therapeutics company, today announced the Health Canada
approval and immediate availability of
ONPATTRO® (patisiran) for the treatment of
polyneuropathy in adult patients with hereditary
transthyretin-mediated (hATTR) amyloidosis3. ONPATTRO is
the only treatment in Canada
indicated for all stages of polyneuropathy associated with hATTR
amyloidosis, a progressive, debilitating, chronic and often fatal
disease. ONPATTRO is based on Nobel Prize-winning science and is
the first ever RNAi therapeutic to be approved in Canada.
"hATTR amyloidosis can progress quickly becoming severely
debilitating, and often leads to premature death," said Dr.
Vera Bril, Professor of Medicine at
the University of Toronto, Director of
Neurology at University Health Network and Mount Sinai Hospital and
the Krembil Family Chair in Neurology. "Having a treatment that can
potentially reverse the course of this life-threatening disease
marks a major advance for my patients, many of whom have crippling
neuropathic pain, struggle to walk unaided and suffer from
countless other symptoms, like diarrhea and vomiting, that
interfere with normal activities of daily living."
hATTR amyloidosis is a multisystemic, progressive disease caused
by mutations that interfere with the way the body manufactures a
specific protein formed in the liver. Known as gene silencing,
RNAi is a new approach to the treatment of the disease, targeting
the faulty protein that causes the disease.
"As a cardiologist with several hereditary TTR amyloidosis
patients with both polyneuropathy and cardiomyopathy, the approval
of ONPATTRO provides a new option for this devastating disease,"
said Dr. Diego Delgado, Cardiologist
at the Peter Munk Cardiac center at the University Health Network.
"Many of my patients have significant disease burden not only in
their heart, but also the nerves. It is exciting to have an
opportunity to halt or even reverse the progression of a disease
that my patients have experienced as a slow march to disability and
death."
Symptoms of hATTR amyloidosis can vary from person to person,
depending on which organs or tissues are affected and can worsen as
the disease progresses. Parts of the body that are typically
affected are the peripheral nervous (nerves), cardiac (heart) and
gastrointestinal (digestive) systems resulting in polyneuropathy
and cardiomyopathy. Specifically, neuropathic changes result in
sensory-motor issues, with challenges in activities of daily
living. Autonomic nerve involvement can lead to low blood pressure,
diarrhea, impotence, and bladder disturbances, while cardiac
symptoms include heart failure and arrhythmias.4
"Imagine looking ahead to a future where your body deteriorates
and you are unlikely to survive the next 5 years! No treatment,
only symptom management. Until recently, this has been the case for
many hATTR patients and their families," said Marsha McWhinnie, Founder of the Canadian
Amyloidosis Support Network (CASN) and Anne
Marie Carr, Founder of the Hereditary Amyloidosis Canada
(HAC) in a joint statement. "Canadian physicians now have
another new treatment option to change the future for their
patients, to give them meaningful improvement in their lives, to
give them hope."
The Health Canada approval was based on results of the APOLLO
Phase 3 study, the largest-ever study in patients with hATTR
amyloidosis. In the pivotal, placebo-controlled study,
148 patients received 0.3 mg/kg of ONPATTRO and
77 patients received placebo administered once every 3 weeks
via intravenous infusion for up to 18 months, with a mean ONPATTRO
exposure of 17.7 months. All patients received premedication with a
corticosteroid, acetaminophen, and H1 and H2
blockers.5 The primary endpoint of the APOLLO study
was the change from baseline in the modified Neuropathy Impairment
Score +7 (mNIS+7), which assesses motor strength, reflexes,
sensation, nerve conduction and postural blood pressure. In the
APOLLO study, ONPATTRO demonstrated significant improvement versus
placebo in polyneuropathy, quality of life, walking, nutritional
status and activities of daily living. More than half of
ONPATTRO patients improved over their own baseline for
polyneuropathy and quality of life with some patients reducing
dependence on or no longer requiring walking aids. The mean (±SD)
mNIS+7 at baseline was 80.9±41.5 in the patisiran group and
74.6±37.0 in the placebo group; the least-squares mean (±SE) change
from baseline was −6.0±1.7 versus 28.0±2.6 (difference, −34.0
points; P<0.001) at 18 months. The mean (±SD) baseline Norfolk
QOL-DN score was 59.6±28.2 in the patisiran group and 55.5±24.3 in
the placebo group; the least-squares mean (±SE) change from
baseline was −6.7±1.8 versus 14.4±2.7 (difference, −21.1 points;
P<0.001) at 18 months.6
The most frequently occurring adverse reactions reported in
ONPATTRO-treated patients (≥ 10% of patients and occurring ≥ 3
percentage points more frequently than in placebo-treated patients)
were peripheral edema and infusion-related
reactions.7 ONPATTRO is the only approved treatment
in Canada that does not require
additional safety monitoring via blood tests.
ONPATTRO was granted Priority Review status by Health Canada,
which is intended for new potentially life-saving treatments where
there is no existing medicine in the Canadian market or where the
new medicine represents a significant improvement in the
benefit/risk profile over existing products.8
"Health Canada's approval of
ONPATTRO underscores our commitment to deliver innovative medicines
with the potential to transform the lives of patients suffering
from hATTR amyloidosis with polyneuropathy," says Jeff Miller, Country Manager, Alnylam Canada.
"It marks a major milestone in Alnylam's history, as the company's
first treatment approved in Canada, but we believe this is just the
beginning. Our vision is to harness the power of RNAi therapeutics
to increase the number of treatment options available for patients
with serious, life-threatening rare diseases where there are
currently limited or no available treatment options. We take pride
in working with the medical and patient community to increase
awareness, enable diagnosis and provide important education and
support services."
About hATTR amyloidosis9
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 a promising
and rapidly advancing frontier in biology and drug development that
has the potential to transform the care of patients with genetic
and other diseases. It was awarded the 2006 Nobel Prize for
Physiology or Medicine.
About ONPATTRO (patisiran)
Patisiran is an
intravenously administered RNAi therapeutic targeting transthyretin
(TTR) for the treatment of hereditary ATTR amyloidosis with
polyneuropathy. It is designed to target and silence specific
messenger RNA, potentially blocking the production of TTR protein
before it is made. Patisiran blocks the production of transthyretin
in the liver, reducing its accumulation in the body's tissues in
order to halt or reverse the progression of the
disease.10
About Alnylam Pharmaceuticals
Alnylam (Nasdaq: ALNY)
is leading the translation of RNA interference (RNAi) into a new
class of innovative medicines with the potential to improve the
lives of people afflicted with rare genetic, cardio-metabolic,
hepatic infectious, and central nervous system (CNS) 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 discovery platform. Alnylam has a deep
pipeline of investigational medicines, including five product
candidates that are in Phase 3 clinical trials and one in
registration. Looking forward, Alnylam will continue to execute 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 employs
over 1200 people worldwide and is headquartered in Cambridge, MA. Alnylam Canada is headquartered
in Mississauga, Ontario with
established operations since June
2018.
###
Alnylam Forward Looking Statements
Various statements
in this release concerning Alnylam's future expectations, plans and
prospects, including, without limitation, Alnylam's plans to launch
ONPATTRO in Canada, the potential
benefits for patients in Canada
for whom ONPATTRO is indicated, and expectations regarding 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, Alnylam's ability
to discover and develop novel drug candidates and delivery
approaches, successfully demonstrate the efficacy and safety of its
product candidates, 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, obtaining, maintaining and protecting
intellectual property, Alnylam's ability to enforce its
intellectual property rights against third parties and defend its
patent portfolio against challenges from third parties, obtaining
and maintaining regulatory approval, pricing and reimbursement for
products, progress in establishing a commercial and ex-United
States infrastructure, successfully launching, marketing and
selling its approved products globally, 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, obtain additional funding
to support its business activities, and establish and maintain
strategic business alliances and new business initiatives,
Alnylam's dependence on third parties for development, manufacture
and distribution of products, 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.
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1 Adams et
al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin
Amyloidosis. New England Journal of Medicine, 379:11-21, July 5,
2018.
|
2
Patisiran Product Monograph, Alnylam Pharmaceuticals Inc, June 7,
2019.
|
3
Patisiran Product Monograph, Alnylam Pharmaceuticals Inc, June 7,
2019.
|
4 Adams et
al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin
Amyloidosis. New England Journal of Medicine, 379:11-21, July 5,
2018.
|
5
Patisiran Product Monograph, Alnylam Pharmaceuticals Inc, June 7,
2019.
|
6 Adams et
al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin
Amyloidosis. New England Journal of Medicine, 379:11-21, July 5,
2018.
|
7
Patisiran Product Monograph, Alnylam Pharmaceuticals Inc, June 7,
2019.
|
8 Health
Canada
https://www.canada.ca/content/dam/hc-sc/migration/hc-sc/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodpharma/prfs_tpfd-eng.pdf
Accessed June 17, 2019.
|
9 The
American Journal of Managed Care
https://www.ncbi.nlm.nih.gov/pubmed/28978215/ Accessed June 17,
2019.
|
10 Adams
et al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin
Amyloidosis. New England Journal of Medicine, 379:11-21, July 5,
2018.
|
SOURCE Alnylam Pharmaceuticals, Inc.