– 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 –
– Alnylam to Host Conference Call Today at 8:30
a.m. ET –
Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), the leading
RNAi therapeutics company, and Sanofi Genzyme, the specialty care
global business unit of Sanofi, 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 5 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.
Conference Call Details
Alnylam management will discuss these results via conference
call on September 20, 2017 at 8:30 a.m. ET. A slide presentation
will also be available on the Investors page of the Company's
website, www.alnylam.com, to accompany the conference call. To
access the call, please dial (877) 312-7507 (domestic) or (631)
813-4828 (international) five minutes prior to the start time and
refer to conference ID 88881001. A replay of the call will be
available beginning at 11:30 a.m. ET on September 20, 2017. To
access the replay, please dial (855) 859-2056 (domestic) or (404)
537-3406 (international), and refer to conference ID 88881001.
About the APOLLO Phase 3 Study
The 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 Patisiran
Patisiran 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 RNAi
RNAi (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 Alnylam Pharmaceuticals
Alnylam (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.
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.
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, Europe
and ROW countries, its expectations regarding the potential for
patisiran to improve the lives of hATTR amyloidosis patients with
polyneuropathy 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 Forward Looking Statements
This 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.
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Alnylam Pharmaceuticals, Inc.Investors and MediaChristine
Regan Lindenboom, 617-682-4340orInvestorsJosh Brodsky,
617-551-8276
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