– Patisiran Achieves a Mean 0.8 Point Decrease
in Modified Neuropathy Impairment Score (mNIS+7) at 18 Months,
Showing Continued Evidence of Potential Halting of Neuropathy
Progression –
– Company Reports First-Ever Clinical
Correlative Evidence that the Degree of TTR Knockdown May Be
Associated with Improvement in mNIS+7 –
– Company to Host Conference Call Today,
Wednesday, April 20, at 8:30 am ET to Discuss Results –
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, announced today complete 18-month data from
its ongoing Phase 2 open-label extension (OLE) study with
patisiran, an investigational RNAi therapeutic targeting
transthyretin (TTR) for the treatment of hereditary ATTR
amyloidosis with polyneuropathy (hATTR-PN), also known as familial
amyloidotic polyneuropathy (FAP). These new clinical data are being
presented in an oral talk at the 68th Annual Meeting of the
American Academy of Neurology (AAN) being held April 15 – 21, 2016
in Vancouver, British Columbia, Canada. Complete 18-month data
(N=27) from the study provide continued evidence that patisiran has
the potential to halt neuropathy progression in patients with
hATTR-PN. In the first reported exploratory analysis of its kind,
the degree of TTR knockdown observed in patients was shown to
correlate with improvement in neuropathy impairment scores.
Further, in this Phase 2 OLE trial, patisiran was found to be
generally well tolerated with up to 25 months of treatment. Dosing
continues in the patisiran Phase 2 OLE study, and the Company plans
to report initial 24-month data from the trial in mid-2016.
"We are pleased to see continued evidence for potential halting
of neuropathy progression after 18 months of treatment in the
ongoing Phase 2 OLE study with patisiran. The mean 0.8-point
decrease in mNIS+7 is an encouraging finding, as the change in
mNIS+7 from baseline to 18 months is the primary endpoint in our
ongoing APOLLO Phase 3 trial with patisiran. Furthermore, the
safety profile of patisiran, with up to 25 months of treatment,
continues to be encouraging,” said Eric Green, Vice President,
General Manager, TTR Program. “In addition, we are excited to share
data from an exploratory analysis showing statistically significant
correlations between the degree of TTR knockdown and improvements
in mNIS+7. Taken together, we believe the data from this ongoing
Phase 2 OLE study further support patisiran’s potential as an
innovative medicine for hATTR-PN, a progressive, debilitating
disease with few treatment options. We look forward to the
continued advancement of patisiran, including the expected readout
of our ongoing APOLLO Phase 3 trial in mid-2017.”
New results presented at the AAN meeting were as of a data cut
off of February 23, 2016, and showed that mean neuropathy
impairment scores were essentially unchanged from baseline values
after 18 months of treatment. Specifically, there was a mean
decrease in mNIS+7 of 0.8 points, which compares favorably to an
estimated mean increase in mNIS+7 of 22 to 26 points over 18 months
based upon analysis of historical data sets in untreated hATTR-PN
patients with similar baseline characteristics. Similar results
were observed in patients with or without concurrent tetramer
stabilizer use. In addition, patisiran administration was
associated with a statistically significant, approximately 77%
median improvement in nerve fiber density as read histologically in
a blinded manner from distal thigh sweat gland biopsy samples (p
less than 0.001). Over the 18 month period, patients with
associated cardiomyopathy (N=11) showed stability in their
echocardiographic, biomarker, and functional measures, including
10-meter-walk speed. Serum TTR levels were also measured throughout
the OLE study, and showed sustained TTR knockdown for over 24
months with a mean maximal knockdown of 92% over the entire period
and a mean post-dose knockdown of 87% at 18 months.
In addition, Alnylam also presented the results of an
exploratory analysis examining the relationship between the degree
of TTR knockdown with subsequent changes in mNIS+7. In the
analysis, inter-subject differences in the degree of TTR knockdown
were compared to changes in mNIS+7 at 6, 12, and 18 months to
assess the effects of patisiran administration. There was a linear
correlation between the degree of serum TTR knockdown and changes
in mNIS+7. Specifically, greater degrees of TTR knockdown resulted
in greater levels of mNIS+7 improvement; these results were
significant at 6 and 12 months (p less than 0.01) and showed a
trend at 18 months (p equal to 0.055). Importantly, this is the
first reported evidence that correlates the degree of TTR knockdown
with improvements in mNIS+7, supporting the therapeutic hypothesis
that reduction of mutant and wild-type TTR may be associated with
potential for a halting of neuropathy progression in patients with
hATTR-PN.
Patisiran administration was also found to be generally well
tolerated in hATTR-PN patients with 18 to up to 25 months of
treatment. Of the most common adverse events reported in 10% or
more of patients, the most frequent drug-related or possibly
drug-related adverse events (AEs) were flushing (22.2%) and
infusion-related reactions (18.5%), which were all mild in severity
and did not result in any discontinuations. There were eight
reports of serious adverse events (SAEs) in five patients, all of
which were unrelated to study drug, including one discontinuation
for gastroesophageal cancer at approximately 20 months in a patient
who subsequently died. After the data cut-off date, an additional
unrelated SAE of myocardial infarction was reported in a 79
year-old patient who subsequently died after having completed the
full 24 months of treatment. Overall, there were no clinically
significant changes in liver function tests, renal function, or
hematologic parameters, including platelets.
To view the 18-month patisiran OLE study results, please visit
www.alnylam.com/capella.
Conference Call InformationAlnylam management will
discuss these data in a webcast conference call on Wednesday,
April 20 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 92074780. A replay of the call will be
available beginning at 10:30 a.m. ET. To access the replay,
please dial 855-859-2056 (domestic) or 404-537-3406
(international), and refer to conference ID 92074780.
About the Patisiran Phase 2 OLE StudyThe ongoing
patisiran Phase 2 OLE study is an open-label, multi-center trial
designed to evaluate the long-term safety and tolerability of
patisiran administration in patients with hereditary ATTR
amyloidosis with polyneuropathy (hATTR-PN) that were previously
enrolled in a Phase 2 study. Patisiran is being administered once
every 3 weeks at a dose of 0.3 mg/kg by intravenous infusion. The
study is measuring a number of clinical endpoints every six months,
including mNIS+7 which is an evaluation of muscle weakness, sensory
and autonomic function, and nerve conductance, where neuropathy
progression leads to an increased score over time. The change in
the mNIS+7 measurement from baseline to 18 months is the primary
endpoint in the company's APOLLO Phase 3 trial of patisiran in
patients with hATTR-PN.
Sanofi Genzyme AllianceIn January 2014, Alnylam and
Sanofi Genzyme, the specialty care global business unit of Sanofi,
formed an alliance to accelerate and expand the development and
commercialization of RNAi therapeutics across the world. The
alliance is structured as a multi-product geographic alliance in
the field of rare diseases. Alnylam retains product rights
in North America and Western Europe, while Sanofi
Genzyme obtained the right to access certain programs in Alnylam's
current and future Genetic Medicines pipeline in the rest of the
world (ROW), including co-development/co-commercialization and/or
global product rights for certain programs. In the case of
patisiran, Alnylam will advance the product in North
America and Western Europe, while Sanofi Genzyme will
advance the product in the ROW.
About hATTRHereditary transthyretin (TTR)-mediated
amyloidosis (hATTR) 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 represents a major unmet medical need with
significant morbidity and mortality; hATTR with polyneuropathy
(hATTR-PN) – also known as familial amyloidotic polyneuropathy
(FAP) – affects approximately 10,000 people worldwide and hATTR
with cardiomyopathy (hATTR-CM) – also known as familial amyloidotic
cardiomyopathy (FAC) – is estimated to affect at least 40,000
people worldwide. hATTR-PN patients have a life expectancy of 5 to
15 years from symptom onset, and the only approved treatment
options for early stage disease are liver transplantation and
tafamidis (approved in Europe, certain countries
in Latin America and Japan, where it is approved for all
stages of disease). hATTR-CM is fatal within 2.5 to 5 years of
diagnosis and treatment is currently limited to supportive care.
Wild-type amyloidosis (wtATTR) – also called senile systemic
amyloidosis (SSA) – is a non-hereditary form of TTR cardiac
amyloidosis caused by idiopathic deposition of wild-type TTR; its
prevalence is generally unknown, but is associated with advanced
age. There is a significant need for novel therapeutics to treat
patients with hATTR.
About LNP TechnologyAlnylam has licenses to Arbutus
Biopharma LNP intellectual property for use in RNAi therapeutic
products using LNP technology.
About RNAiRNAi (RNA interference) is a revolution in
biology, representing a breakthrough in understanding how genes are
turned on and off 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, thereby preventing
disease-causing proteins from being made. RNAi therapeutics have
the potential to treat disease and help patients in a fundamentally
new way.
About Alnylam PharmaceuticalsAlnylam is a
biopharmaceutical company developing novel therapeutics based on
RNA interference, or RNAi. The company is leading the translation
of RNAi as a new class of innovative medicines. Alnylam's pipeline
of investigational RNAi therapeutics is focused in 3 Strategic
Therapeutic Areas (STArs): Genetic Medicines, with a broad pipeline
of RNAi therapeutics for the treatment of rare diseases;
Cardio-Metabolic Disease, with a pipeline of RNAi therapeutics
toward genetically validated, liver-expressed disease targets for
unmet needs in cardiovascular and metabolic diseases; and Hepatic
Infectious Disease, with a pipeline of RNAi therapeutics that
address the major global health challenges of hepatic infectious
diseases. In early 2015, Alnylam launched its "Alnylam 2020"
guidance for the advancement and commercialization of RNAi
therapeutics as a whole new class of innovative medicines.
Specifically, by the end of 2020, Alnylam expects to achieve a
company profile with 3 marketed products, 10 RNAi therapeutic
clinical programs – including 4 in late stages of development –
across its 3 STArs. The company's demonstrated commitment to RNAi
therapeutics has enabled it to form major alliances with leading
companies including Ionis, Novartis, Roche, Takeda, Merck,
Monsanto, The Medicines Company, and Sanofi Genzyme. In addition,
Alnylam holds an equity position in Regulus Therapeutics Inc., a
company focused on discovery, development, and commercialization of
microRNA therapeutics. Alnylam scientists and collaborators have
published their research on RNAi therapeutics in over 200
peer-reviewed papers, including many in the world's top scientific
journals such as Nature, Nature Medicine, Nature Biotechnology,
Cell, New England Journal of Medicine, and The Lancet. Founded in
2002, Alnylam maintains headquarters in Cambridge, Massachusetts.
For more information about Alnylam's pipeline of investigational
RNAi therapeutics, please visit www.alnylam.com.
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 potential for RNAi therapeutics, including the
potential of patisiran to halt neuropathy progression in patients
with hATTR-PN, expectations regarding the reporting of data from
the ongoing Phase 2 open-label extension trial and APOLLO Phase 3
trial with patisiran, its expectations regarding its STAr pipeline
growth strategy, and its plans regarding 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 may differ materially
from those indicated by these forward-looking statements as a
result of various important 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 drug 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,
actions of regulatory agencies, which may affect the initiation,
timing and progress of clinical trials, obtaining, maintaining and
protecting intellectual property, Alnylam's ability to enforce its
patents against infringers and defend its patent portfolio against
challenges from third parties, obtaining regulatory approval for
products, competition from others using technology similar to
Alnylam's and others developing products for similar uses,
Alnylam's ability to manage operating expenses, Alnylam's ability
to 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, marketing, sales and distribution of
products, the outcome of litigation, and unexpected expenditures,
as well as those risks more fully discussed in the "Risk Factors"
filed with Alnylam's most recent Annual Report on Form 10-K 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 to
update any forward-looking statements.
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version on businesswire.com: http://www.businesswire.com/news/home/20160420005162/en/
Alnylam Pharmaceuticals, Inc.Investors and MediaChristine
Regan Lindenboom, 617-682-4340orInvestorsJosh Brodsky,
617-551-8276
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