− In Patients with Hereditary ATTR Amyloidosis,
Patisiran Treatment Improved Polyneuropathy and Quality of Life
Relative to Placebo −
− Majority of Patients Receiving Patisiran
Experienced Improvement in Polyneuropathy and Quality of Life
Relative to Baseline −
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading
RNAi therapeutics company, announced today that the pivotal study
results from the APOLLO Phase 3 trial of patisiran were published
online today in The New England Journal of Medicine (NEJM). The
study showed that patisiran improved measures of polyneuropathy,
quality of life, activities of daily living, ambulation,
nutritional status, and autonomic symptoms relative to placebo in
patients with hereditary transthyretin-mediated (hATTR)
amyloidosis, an inevitably progressive and generally fatal disease.
Patisiran treatment also led to favorable effects on exploratory
endpoints related to cardiac structure and function in patients
with cardiac involvement. Further, the frequency and severity of
adverse events (AEs) were similar in patients receiving patisiran
and placebo, with the exception of peripheral edema and
infusion-related events which were higher in patisiran-treated
patients and generally mild to moderate in severity. The full
manuscript, titled "Patisiran, an RNAi Therapeutic, for Hereditary
Transthyretin Amyloidosis," will appear in the July 5, 2018 issue
of NEJM.
“The publication of the APOLLO study results in NEJM underscores
the potential for clinical benefit and the encouraging safety
profile of patisiran, and reinforces the strong therapeutic
potential of this investigational medicine for people living with
hATTR amyloidosis,” said David Adams M.D., Ph.D., Department
of Neurology, Coordinator of the national reference center for
Familial Amyloid Polyneuropathy (FAP) and rare neuropathies,
Bicêtre Hospital, Greater Paris University Hospitals, AP-HP,
Principal Investigator for the APOLLO trial, and lead author of the
manuscript. “The positive impact on both neurologic impairment and
quality of life in patients treated with patisiran was in marked
contrast to the disease progression seen in placebo-treated
patients in just 18 months. In fact, we observed improvement in
neuropathy manifestations and quality of life in a majority of
patisiran-treated patients, with some patients showing evidence of
halting or reversal of neuropathy progression during the study,
including a transition from assisted to unassisted walking. The
broad, international patient population recruited to APOLLO is
characteristic of the wide disease spectrum seen in clinical
practice, supporting the relevance of the potential beneficial
effects of patisiran for patients worldwide afflicted with this
progressive and generally fatal disease.”
“We are extremely pleased with the publication of this landmark
manuscript, the first-ever pivotal RNAi clinical trial to be
published in a top-tier, peer-reviewed medical journal,” said
Akshay Vaishnaw, M.D., Ph.D., President of Research and Development
at Alnylam. “Publication of the APOLLO study results in NEJM is a
testament to Alnylam's decade-long effort and unwavering commitment
to patients with hATTR amyloidosis, and to the goal of advancing an
innovative new class of medicines that harnesses the natural RNAi
mechanism of action to silence production of disease-causing
proteins. Further, publication of these comprehensive efficacy and
safety results highlights our commitment to scientific and clinical
excellence, and the importance we place on data transparency. This
work would not have been possible without all the patients and
investigators who participated in APOLLO, and we are deeply
indebted to them.”
The APOLLO study publication presents robust evidence for
patisiran’s potential to treat a broad constellation of hATTR
amyloidosis clinical manifestations and their disabling effects.
Relative to placebo, data from APOLLO showed that treatment with
patisiran resulted in significant and clinically meaningful
improvements in measures of polyneuropathy and quality of life. In
addition, compared to baseline and after 18 months of patisiran
treatment, improvement was observed in a majority of patients in
the primary endpoint, mNIS+7 score (a composite measure of
neuropathy), and in the key secondary endpoint, Norfolk QOL-DN (a
quality of life questionnaire). The improvement in mNIS+7 was shown
to be correlated with degree of TTR knockdown. Significant effects
on muscle strength, activities of daily living, ambulation,
nutritional status, and autonomic symptoms were also noted in
patisiran patients relative to placebo. Moreover, patisiran
patients with echocardiographic evidence of cardiac amyloid
involvement at study entry demonstrated favorable effects on
exploratory endpoints related to cardiac structure and function
when compared to placebo.
A lower proportion of patients randomized to patisiran than
placebo discontinued treatment (7 versus 38 percent) and
discontinued the study (7 versus 29 percent). The incidence and
severity of AEs and the frequency of serious AEs (SAEs) and deaths
were similar in patisiran- and placebo-treated patients. Compared
to placebo, patisiran treatment was associated with fewer treatment
discontinuations (5 versus 14 percent) due to AEs. The AEs
occurring more frequently with patisiran than placebo were
peripheral edema (30 versus 22 percent) and infusion-related
reactions (IRRs; 19 versus 9 percent) both of which were generally
mild to moderate in severity. IRRs decreased over time and led to
study withdrawal in one patient (0.7 percent). No
clinically-relevant changes in laboratory values related to
patisiran treatment, including platelet counts and liver and kidney
function tests, were observed during the study.
About the APOLLO Phase 3 StudyThe APOLLO Phase 3 trial
was a randomized, double-blind, placebo-controlled, global study
designed to evaluate the efficacy and safety of patisiran in hATTR
amyloidosis patients with polyneuropathy. The primary endpoint of
the study was the change from baseline in modified Neuropathy
Impairment Score +7 (mNIS+7) relative to placebo at 18 months.
Secondary endpoints included: the Norfolk Quality of Life-Diabetic
Neuropathy (QOL-DN) score; NIS-weakness (NIS-W); Rasch-built
Overall Disability Scale (R-ODS); timed 10-meter walk (10-MWT);
modified BMI (mBMI); and the composite autonomic symptom score-31
(COMPASS-31). In addition, exploratory cardiac assessments included
measurement of N-terminal pro-brain natriuretic peptide (NT-ProBNP)
levels and echocardiography. The trial enrolled 225 hATTR
amyloidosis patients in 19 countries with 39 genotypes who were
randomized 2:1, patisiran:placebo, with patisiran administered at
0.3 mg/kg intravenously once every three weeks for 18 months. All
patients who completed the APOLLO Phase 3 study were eligible to
screen for the Global OLE study, in which they have the opportunity
to receive patisiran on an ongoing basis.
About PatisiranPatisiran is an investigational,
intravenously administered RNAi therapeutic targeting transthyretin
(TTR) in development for the treatment of hereditary ATTR
amyloidosis. It is designed to target and silence specific
messenger RNA, potentially blocking the production of TTR protein
before it is made. This may help to reduce the deposition and
facilitate the clearance of TTR amyloid in peripheral tissues and
potentially restore function to these tissues. Patisiran is
currently under Priority Review as a Breakthrough Therapy with the
U.S. Food and Drug Administration (FDA) and under accelerated
assessment by the European Medicines Agency (EMA) for the treatment
of patients with hATTR amyloidosis. The FDA has set a PDUFA date of
August 11, 2018. The safety and efficacy of patisiran have not been
evaluated by the FDA or any other health authority.
About hATTR amyloidosisHereditary 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 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. The only available treatment
options for early stage disease are liver transplantation and, in
some countries, tafamidis (approved in Europe, and certain
countries in Asia and Latin America, specific indication varies by
region). As such, there is a significant need for novel
therapeutics to help treat patients with hATTR amyloidosis.
About RNAiRNAi (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 major new class of medicines, known as
RNAi therapeutics, is on the horizon. 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 Alnylam PharmaceuticalsAlnylam (Nasdaq: ALNY) is
leading 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 genetic, cardio-metabolic, and
hepatic infectious 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 and deep pipeline of investigational
medicines, including four product candidates that are in late-stage
development. 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 800 people in the U.S. and Europe and 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 or on LinkedIn.
Alnylam Forward Looking StatementsVarious statements in
this release concerning Alnylam's future expectations, plans and
prospects, including, without limitation, Alnylam's views with
respect to the results from its APOLLO Phase 3 clinical trial for
patisiran, the publication of such results, and the potential
implications of such results for patients, its expectations
concerning the review of patisiran by regulatory authorities in the
United States and Europe, its expectations regarding the potential
for patisiran to improve the lives of hATTR amyloidosis patients
and their families, its plans for the commercialization of
patisiran if approved by regulatory authorities, 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, 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.
Patisiran has not been approved by the FDA, EMA, or any other
regulatory authority and no conclusions can or should be drawn
regarding the safety or effectiveness of this investigational
therapeutic.
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version on businesswire.com: https://www.businesswire.com/news/home/20180704005373/en/
Alnylam Pharmaceuticals, Inc.Christine Regan Lindenboom,
617-682-4340(Investors and Media)orJosh Brodsky,
617-551-8276(Investors)
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