CAMBRIDGE, Mass. & TOKYO--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved ONPATTRO® (patisiran) for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy. ONPATTRO is the first approved RNAi therapeutic in Japan and Alnylam will launch and directly market it in the country.
“hATTR amyloidosis is a genetic disease that can cause a variety of debilitating symptoms and can often be fatal. Historically, treatment options for people living with this condition in Japan, where the V30M mutation of the condition is prevalent, were limited,” said Professor Yukio Ando, President of ISA (International Society of Amyloidosis) and JSA (Japan Society of Amyloidosis), Chairman and Professor/Department of Amyloidosis Research of Nagasaki International University and Professor Emeritus and Visiting Professor of Kumamoto University, Japan. “The approval of ONPATTRO, a treatment that has the potential to mitigate and potentially reverse symptoms of polyneuropathy and to improve quality of life, marks a paradigm shift in the way we approach and treat this serious disease.”
“We are very excited about the approval of ONPATTRO and are proud to be bringing this important new treatment to patients with hATTR amyloidosis with polyneuropathy in Japan,” said Masako Nakamura, Senior Vice President, Head of Asia, Alnylam. “With this approval, we look forward to working with the hATTR amyloidosis community to continue to raise disease awareness, increase diagnosis rates and ultimately provide treatment to patients suffering from this devastating disease. This is a significant milestone in our efforts to bring RNAi therapeutics to people around the world and we look forward to continuing to build our presence in Asia.”
Alnylam submitted a New Drug Application (NDA) to Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) on September 27, 2018 based on the results from the APOLLO Phase 3 study, which evaluated the efficacy and safety of patisiran in hATTR amyloidosis patients with polyneuropathy. Results from the APOLLO study were published in the July 5, 2018, issue of The New England Journal of Medicine. Patisiran had previously received orphan drug designation from the MHLW, which made it eligible for priority review as well as 10 years of market exclusivity in Japan.
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 ONPATTRO® (Patisiran)
Patisiran,
based on Nobel Prize-winning science, is an intravenously administered
RNAi therapeutic targeting transthyretin (TTR) for the treatment of
hereditary ATTR amyloidosis. It is designed to target and silence TTR
messenger RNA, thereby blocking the production of TTR protein before it
is made. Patisiran 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 disease. In August 2018, Patisiran received U.S. Food
and Drug Administration (FDA) approval for the treatment of the
polyneuropathy of hATTR amyloidosis in adults, as well as European
Medicines Agency marketing authorization for the treatment of hATTR
amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy. Patisiran
was approved in Japan in June 2019 for the treatment of hereditary
transthyretin-mediated (hATTR) amyloidosis with polyneuropathy.
IMPORTANT SAFETY INFORMATION
ONPATTRO is a medicine that
treats the polyneuropathy caused by an illness called hereditary
transthyretin-mediated amyloidosis (hATTR amyloidosis). ONPATTRO is used
in adults only.
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, paracetamol, 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 respiratory-tract
infection (29 percent) and infusion-related reactions (19 percent).
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 transform the lives of people
afflicted with rare genetic, cardio-metabolic, hepatic infectious, and
central nervous system/ocular diseases. Based on Nobel Prizewinning
science, RNAi therapeutics represent a powerful, clinically validated
approach for the treatment of diseases with high unmet need. ONPATTRO®
(patisiran) is the first-ever RNAi therapeutic approved by the U.S. FDA
for the treatment of the polyneuropathy of hereditary
transthyretin-mediated (hATTR) amyloidosis in adults and by the EMA for
the treatment of hATTR amyloidosis in adults with stage 1 or stage 2
polyneuropathy. Alnylam has a deep pipeline of investigational
medicines, including five product candidates in Phase 3 studies 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. Headquartered
in Cambridge, MA, Alnylam employs over 1,200 people worldwide. 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 concerning Alnylam's future expectations, plans and
prospects, including, without limitation, Alnylam's plans to launch
ONPATTRO (patisiran) in Japan, plans to increase awareness of hATTR
amyloidosis, increase diagnosis rates and increase Alnylam’s presence in
Japan, 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 or marketing
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.
