Sanofi and Alnylam Report Positive Topline
Results from APOLLO Phase 3 Study of Patisiran in Hereditary ATTR
(hATTR) Amyloidosis Patients with Polyneuropathy
- Investigational RNAi Therapeutic Patisiran
Meets Primary and All Secondary Endpoints, with Highly Significant
Reduction In Neuropathy Progression and Improvement in Quality of
Life at 18 Months Relative to Placebo -
- Alnylam Intends to File New Drug Application
(NDA) in Late 2017 and Marketing Authorisation Application (MAA) in
Early 2018 -
- Full Results to be Presented at 1st European
ATTR Amyloidosis Meeting in November -
Paris, France and Cambridge, MA - September
20, 2017 - Sanofi Genzyme, the specialty care global business
unit of Sanofi, and Alnylam Pharmaceuticals,
Inc. (Nasdaq:ALNY), the leading RNAi therapeutics company
announced today that the APOLLO Phase 3 study of patisiran, an
investigational RNAi therapeutic being developed for patients with
hereditary ATTR amyloidosis with polyneuropathy, met its primary
efficacy endpoint and all secondary endpoints. The primary endpoint
for the study was the change from baseline in the modified
neuropathy impairment score (mNIS+7) at 18 months. The key
secondary endpoint was improvement in quality of life assessed by
the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy
(Norfolk QOL-DN).
"We are very proud to report the first ever
positive Phase 3 results for an RNAi therapeutic, marking the
potential arrival of an entirely new class of medicines. This
moment is the culmination of a 15-year journey of tireless work by
countless contributors who have overcome enormous scientific and
business challenges to make RNAi therapeutics a reality," said John
Maraganore, Ph.D., Chief Executive Officer of Alnylam. "This is an
incredibly exciting milestone for Alnylam and RNAi, and most
importantly for patients and their treating physicians and
families. We extend our deepest gratitude to all the patients,
investigators and study staff who participated in the APOLLO study
- they made this important scientific progress possible."
The APOLLO trial enrolled 225 hATTR amyloidosis
patients with polyneuropathy, representing 39 genotypes, at 44
study sites in 19 countries around the world. Patients were
randomized 2:1 to patisiran or placebo, with patisiran administered
intravenously at 0.3 mg/kg once every three weeks for 18 months.
For both the mNIS+7 and Norfolk QOL-DN endpoint measures provided
below, a lower score indicates a better clinical result.
- At 18 months, the mean change from baseline in mNIS+7 was
significantly lower in the patisiran group as compared with placebo
(p less than 0.00001).
- The mean and median changes in mNIS+7 impairment scores for
patisiran both achieved negative values, indicating an improvement
overall and in the majority of patients compared with baseline.
- Patients in the patisiran group experienced improvement in
quality of life compared to placebo, as assessed by the Norfolk
Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN)
(p less than 0.00001).
- The mean and median changes in QOL scores for patisiran also
both achieved negative values, indicating an improvement overall
and in the majority of patients compared with baseline.
- All five other secondary endpoints also demonstrated
statistically significant favorable differences in the patisiran
arm compared to placebo (p less than 0.001). These were:
- NIS-W, the subdomain of mNIS+7 assessing muscle strength;
- Rasch-built Overall Disability Scale (R-ODS), a patient
reported outcome measure of daily living and disability;
- 10-meter walk test, assessing gait speed;
- Modified body mass index (mBMI), assessing nutritional status;
and
- COMPASS-31, a questionnaire to assess autonomic symptoms.
- The overall safety profile of patisiran was encouraging.
- The patisiran and placebo arms had similar frequencies of
adverse events (AEs) (96.6 percent and 97.4 percent, respectively)
and serious adverse events (SAEs) (36.5 percent and 40.3 percent,
respectively).
- The frequency of deaths in the study was similar in the
patisiran (4.7 percent) and placebo (7.8 percent) arms.
- Patisiran treatment was associated with fewer discontinuations
from treatment compared with placebo (7.4 percent and 37.7 percent,
respectively) and discontinuations from treatment due to AEs (4.7
percent and 14.3 percent, respectively).
- AEs reported in greater than 10 percent of patients and seen
more frequently with patisiran compared with placebo were
peripheral edema (29.7 percent vs. 22.1 percent, respectively) and
infusion-related reactions (18.9 percent vs. 9.1 percent,
respectively), both of which were generally mild-to-moderate in
severity.
"Patients living with hATTR amyloidosis face an
inevitable and painful advancement of their debilitating disease,"
said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President,
R&D of Alnylam. "We believe the very encouraging APOLLO data
demonstrate the potential for investigational patisiran to help
improve the lives of hereditary ATTR amyloidosis polyneuropathy
patients. Our immediate objective is now to submit these data to
global health authorities."
Based on these positive results, Alnylam expects
to file its first New Drug Application in late 2017 and first
Marketing Authorisation Application shortly thereafter. Sanofi
Genzyme is currently preparing for regulatory filings for patisiran
in Japan, Brazil and other countries, to begin in the first half of
2018. Pending regulatory approvals, Alnylam will
commercialize patisiran in the U.S., Canada and Western Europe,
with Sanofi Genzyme commercializing the product in the rest of the
world.
"This is a significant milestone that supports
our belief that RNAi therapeutics have the potential to become an
innovative new class of medicines for patients with rare genetic
diseases," said Elias Zerhouni, M.D., President, Global R&D,
Sanofi. "The APOLLO data suggest that patisiran could help improve
the lives of people living with hATTR amyloidosis with
polyneuropathy, a patient population in urgent need of additional
treatment options. We look forward to working with Alnylam to make
patisiran available around the globe as quickly as possible."
Full results, including data from an exploratory
analysis of the subgroup of patients with cardiac involvement, will
be presented at the 1st European ATTR Amyloidosis Meeting for
Patients and Doctors, on November 2,2017 in Paris, France.
APOLLO is the largest randomized study ever
completed in this disease. Nearly all eligible patients who
completed APOLLO have rolled over to the APOLLO-Open Label
Extension (OLE) study and continue to receive patisiran.
About the APOLLO Phase 3 StudyThe APOLLO Phase 3 study is
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 efficacy
endpoint was change from baseline in the mNIS+7 composite
neuropathy impairment score at 18 months. Modified NIS+7 is a
composite measure of neurologic impairment that evaluates
sensorimotor capabilities, nerve conduction, reflexes, and
autonomic function. Secondary endpoints included the Norfolk QOL DN
quality of life score as well as measures of motor strength (NIS
W), disability (R ODS), gait speed (10 meter walk test),
nutritional status (mBMI) and autonomic symptoms (COMPASS 31).
Exploratory endpoints included cardiac measures in patients with
evidence of cardiac involvement at baseline as well as measures of
dermal amyloid burden and nerve fiber density in skin biopsies.
About PatisiranPatisiran is an investigational medicine
that uses the body's natural processes to lower the levels of the
TTR protein that causes TTR 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
enable the clearance of TTR amyloid deposits in peripheral tissues
and potentially restore function to these tissues. The safety and
efficacy of patisiran have not been evaluated by the U.S. Food and
Drug Administration or any other health authority.
About hATTR amyloidosis Hereditary transthyretin
(TTR)-mediated (hATTR) amyloidosis is an inherited, progressively
debilitating, and often fatal disease caused by mutations in the
TTR gene. TTR protein is produced primarily in the liver and is
normally a carrier of vitamin A. Mutations in TTR 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. hATTR amyloidosis represents a major unmet medical
need with significant morbidity and mortality, affecting
approximately 50,000 people worldwide. hATTR amyloidosis patients
have a life expectancy of 2.5 to 15 years from symptom onset, and
the only approved treatment options are liver transplantation for
early stage disease and tafamidis (approved in Europe, Japan and
certain countries in Latin America, specific indication varies by
region). There is a significant need for novel therapeutics to help
treat patients with hATTR amyloidosis.
About LNP Technology Alnylam has licenses to Arbutus
Biopharma LNP intellectual property for use in RNAi therapeutic
products using LNP technology.
Alnylam - Sanofi Genzyme Alliance In January 2014,
Alnylam and Sanofi Genzyme, the specialty care global business unit
of Sanofi, formed an alliance to accelerate the advancement of RNAi
therapeutics as a potential new class of innovative medicines for
patients around the world with rare genetic diseases. The alliance
enables Sanofi Genzyme to expand its rare disease pipeline with
Alnylam's novel RNAi technology and provides access to Alnylam's
R&D engine, while Alnylam benefits from Sanofi Genzyme's proven
global capabilities to advance late-stage development and, upon
commercialization, accelerate market access for these promising
genetic medicine products. In the case of patisiran, Alnylam will
advance the product in the United States, Canada and Western
Europe, while Sanofi Genzyme will advance the product in the rest
of the world.
About RNAiRNAi (RNA interference) is a
revolution in biology, representing a breakthrough in understanding
protein synthesis in cells, and a completely new approach to drug
discovery and development. Its discovery has been heralded as "a
major scientific breakthrough that happens once every decade or
so," and represents one of the most promising and rapidly advancing
frontiers in biology and drug discovery today which was awarded the
2006 Nobel Prize for Physiology or Medicine. RNAi is a natural
process of gene silencing that occurs in organisms ranging from
plants to mammals. By harnessing the natural biological process of
RNAi occurring in our cells, the creation of 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, target the cause of
diseases by potently silencing specific mRNAs, with the goal of
preventing disease-causing proteins from being made.
About Sanofi Sanofi, a global healthcare
leader, discovers, develops and distributes therapeutic solutions
focused on patients' needs. Sanofi is organized into five global
business units: Diabetes and Cardiovascular, General Medicines and
Emerging Markets, Sanofi Genzyme, Sanofi Pasteur and Consumer
Healthcare. Sanofi is listed in Paris (EURONEXT: SAN) and in New
York (NYSE: SNY).
Sanofi Genzyme focuses on developing specialty
treatments for debilitating diseases that are often difficult to
diagnose and treat, providing hope to patients and their families.
Learn more at www.sanofigenzyme.com.
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 patients who have limited or
inadequate treatment options. Based on Nobel Prize-winning science,
RNAi therapeutics represent a powerful, clinically validated
approach for the treatment of a wide range of 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 three product candidates that are in late-stage
development or will be in 2017. 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. For more information
about our people, science and pipeline, please
visit www.alnylam.com and engage with us on Twitter at
@Alnylam.
Sanofi Forward-Looking StatementsThis press release
contains forward-looking statements as defined in the Private
Securities Litigation Reform Act of 1995, as amended.
Forward-looking statements are statements that are not historical
facts. These statements include projections and estimates regarding
the clinical development of and potential marketing approvals for
the product. Forward-looking statements are generally identified by
the words "expects", "anticipates", "believes", "intends",
"estimates", "plans", "would be" and similar expressions. Although
Sanofi's management believes that the expectations reflected in
such forward-looking statements are reasonable, investors are
cautioned that forward-looking information and statements are
subject to various risks and uncertainties, many of which are
difficult to predict and generally beyond the control of Sanofi,
that could cause actual results and developments to differ
materially from those expressed in, or implied or projected by, the
forward-looking information and statements. These risks and
uncertainties include among other things, the uncertainties
inherent in research and development of the product, future
clinical data and analysis, including post marketing, decisions by
regulatory authorities, such as the FDA or the EMA, regarding
whether and when to approve the product or biological application
that may be filed for the product as well as their decisions
regarding labeling and other matters that could affect the
availability or commercial potential of the product, the absence of
guarantee that the product if approved will be commercially
successful, risks associated with intellectual property, future
litigation, the future approval and commercial success of
therapeutic alternatives, and volatile economic conditions, as well
as those risks discussed or identified in the public filings with
the SEC and the AMF made by Sanofi, including those listed under
"Risk Factors" and "Cautionary Statement Regarding Forward-Looking
Statements" in Sanofi's annual report on Form 20-F for the year
ended December 31, 2016. Other than as required by applicable law,
Sanofi does not undertake any obligation to update or revise any
forward-looking information or statements.
Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam's future
expectations, plans and prospects, including, without limitation,
Alnylam's views with respect to the topline results from its APOLLO
Phase 3 clinical trial for patisiran, its plans for and the
expected timing of regulatory filings seeking approval for
patisiran from regulatory authorities in the United States and
Europe and ROW countries, its expectations regarding the potential
for patisiran to improve the lives of hATTR amyloidosis
polyneuropathy 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 U.S. Food
and Drug Administration, European Medicines Agency, or any other
regulatory authority and no conclusions can or should be drawn
regarding the safety or effectiveness of this investigational
therapeutic.
Sanofi Contacts
Media
RelationsAshleigh KossTel. : +1 (908) 981-8745Mobile: +1
(908) 205-2572Ashleigh.koss@sanofi.com Sanofi Genzyme
Communications Lisa Clemence Tel.: +1 (617)
768-6699Lisa.clemence@sanofi.com |
Investor RelationsGeorge Grofik+33 (0)1 53 77 45
45ir@sanofi.com |
Alnylam Contacts
Investor and Media Relations Christine Regan LindenboomTel.
: +1 (617) 682-4340 |
Investor
RelationsJosh BrodskyTel. : +1 (617) 551-8276 |
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