- Company Achieves Important Milestone in Alnylam 5x15(TM) Product
Strategy by Advancing Second Generation Lipid Nanoparticles to Clinical
Stage, with Data Expected by Year's End -
CAMBRIDGE, Mass., Jul 11, 2011 (BUSINESS WIRE) --
Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics
company, announced today that it has filed a Clinical Trial Application
(CTA) with the Medicines and Healthcare products Regulatory Agency
(MHRA) to initiate a Phase I clinical trial with ALN-PCS, an RNAi
therapeutic for the treatment of severe hypercholesterolemia. Upon
receiving clearance of the CTA, Alnylam plans to initiate the Phase I
trial and expects to present initial safety, tolerability, and clinical
activity data from this study by the end of this year.
"The filing of this CTA marks an important milestone in our Alnylam 5x15
product efforts, as it is the first program using our second generation
lipid nanoparticle technology to enter clinical testing, where we aim to
have important safety, tolerability, and clinical activity data by
year's end. Moreover, we are excited about the potential for ALN-PCS to
make an impact in the treatment of severe hypercholesterolemia as this
RNAi therapeutic targets both intracellular and extracellular PCSK9, a
target validated by human genetics that is known to play a central role
in LDL cholesterol metabolism," said Akshay K. Vaishnaw, M.D., Ph.D.,
Senior Vice President and Chief Medical Officer of Alnylam. "We continue
to execute on our Alnylam 5x15 initiative, which is focused on advancing
innovative RNAi therapeutics that address genetically defined targets
and diseases with high unmet medical need. ALN-PCS represents the second
of such programs, following ALN-TTR01 which is currently in a Phase I
trial with data expected later this quarter."
ALN-PCS is a systemically delivered RNAi therapeutic targeting the gene
proprotein convertase subtilisin/kexin type 9, or PCSK9, a target
validated by human genetics that is involved in the metabolism of
low-density lipoprotein cholesterol (LDLc, or "bad" cholesterol).
ALN-PCS targets both intracellular and extracellular PCSK9, thereby
phenocopying the human genetics observed in loss of function or null
human PCSK9 mutations (N. Engl. J. Med. (2006) 354:1264-1272; Am.
J. Hum. Genet. (2006) 79: 514-523), without any adverse effects on
high-density lipoprotein (HDL, or "good" cholesterol) levels. An RNAi
therapeutic targeting PCSK9 has the potential to lower tissue and
circulating plasma PCSK9 protein levels resulting in higher LDL receptor
levels in the liver, and subsequently lower LDLc levels. Lower LDLc is
associated with a decreased risk of cardiovascular disease, including
myocardial infarction. Pre-clinical data from the ALN-PCS program have
shown specific silencing of PCSK9 mRNA in the liver, and plasma PCSK9
protein levels of up to 90%, with an ED50 (the dose that provides a 50%
silencing effect) of approximately 0.06 mg/kg for both mRNA and protein
reduction. These studies have also demonstrated a greater than 50%
reduction in levels of LDLc, which is rapid and durable, lasting for
weeks after a single dose.
As per the filed CTA, the Phase I trial of ALN-PCS is expected to be
conducted in the U.K. as a randomized, single-blind, placebo-controlled,
single ascending dose study, enrolling approximately 32 healthy
volunteer subjects with elevated baseline LDLc (>116mg/dL). The primary
objective of the study is to evaluate the safety and tolerability of a
single dose of ALN-PCS, with patients being enrolled into five
sequential cohorts of increasing doses ranging from 0.015 to 0.25 mg/kg.
Secondary objectives include characterization of plasma and urine
pharmacokinetics of ALN-PCS, and assessment of pharmacodynamic effects
of the drug on plasma PCSK9 protein and LDLc levels measured from serial
blood samples prior to and following dosing.
ALN-PCS is an RNAi therapeutic that utilizes proprietary Alnylam
second-generation lipid nanoparticle (LNP) technology, specifically that
using the MC3 lipid.
About Severe Hypercholesterolemia
Severe hypercholesterolemia is a condition characterized by very high
levels of cholesterol in the blood which is known to increase the risk
of coronary artery disease, the leading cause of death in the U.S. Most
forms of hypercholesterolemia can be treated through dietary
restrictions and medicines such as statins. However, a large proportion
of patients with hypercholesterolemia are not being met by statin
therapy including genetic familial hypercholesterolemia patients, acute
coronary syndrome patients, and other patient populations that are
statin intolerant or statin resistant; severe hypercholesterolemia is
estimated to affect more than 500,000 patients worldwide. As a result,
there is a significant need for novel therapeutics to treat patients
with severe hypercholesterolemia whose disease is inadequately managed
by existing therapies.
About "Alnylam 5x15(TM)"
The "Alnylam 5x15" strategy, launched in January 2011, establishes a
path for development and commercialization of novel RNAi therapeutics to
address genetically defined diseases with high unmet medical need.
Products arising from this initiative share several key characteristics
including: a genetically defined target and disease; the potential to
have a major impact in a high unmet need population; the ability to
leverage the existing Alnylam RNAi delivery platform; the opportunity to
monitor an early biomarker in Phase I clinical trials for human proof of
concept; and the existence of clinically relevant endpoints for the
filing of a new drug application (NDA) with a focused patient database
and possible accelerated paths for commercialization. This strategy
leverages Alnylam's clinical progress on siRNA delivery, including
definitive human proof-of-concept data for systemic delivery. By the end
of 2015, the company expects to have five such RNAi therapeutic programs
in advanced clinical development. These include ALN-TTR for the
treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the
treatment of severe hypercholesterolemia, ALN-HPN for the treatment of
refractory anemia, and two additional programs from the company's
ongoing discovery efforts that will be designated and advanced into
development later in 2011. Alnylam intends to commercialize the products
arising under the "Alnylam 5x15" strategy itself in the United States
and potentially certain other countries; the company will seek
development and commercial partners in other global territories.
About RNA Interference (RNAi)
RNAi (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 RNAs (siRNAs), 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 Pharmaceuticals
Alnylam 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 with a core
focus on RNAi therapeutics for the treatment of genetically defined
diseases, including ALN-TTR for the treatment of transthyretin-mediated
amyloidosis (ATTR), ALN-PCS for the treatment of severe
hypercholesterolemia, and ALN-HPN for the treatment of refractory
anemia. As part of its "Alnylam 5x15TM" strategy, the company
expects to have five RNAi therapeutic products for genetically defined
diseases in advanced stages of clinical development by the end of 2015.
Alnylam has additional partner-based programs in clinical or development
stages, including ALN-RSV01 for the treatment of respiratory syncytial
virus (RSV) infection, ALN-VSP for the treatment of liver cancers, and
ALN-HTT for the treatment of Huntington's disease. The company's
leadership position on RNAi therapeutics and intellectual property have
enabled it to form major alliances with leading companies including
Merck, Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko
Kirin, and Cubist. In addition, Alnylam and Isis co-founded Regulus
Therapeutics Inc., a company focused on discovery, development, and
commercialization of microRNA therapeutics; Regulus has formed
partnerships with GlaxoSmithKline and sanofi-aventis. Alnylam has also
formed Alnylam Biotherapeutics, a division of the company focused on the
development of RNAi technologies for application in biologics
manufacturing, including recombinant proteins and monoclonal antibodies.
Alnylam scientists and collaborators have published their research on
RNAi therapeutics in over 100 peer-reviewed papers, including many in
the world's top scientific journals such as Nature, Nature
Medicine, Nature Biotechnology, and Cell. Founded in
2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For
more information, please visit www.alnylam.com.
Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam's future
expectations, plans and prospects, including without limitation,
statements regarding Alnylam's expectations with respect to its "Alnylam
5x15" product strategy, Alnylam's views with respect to the potential
for RNAi therapeutics, including ALN-PCS, as well as ALN-TTR01, its
expectations with respect to the timing and success of its clinical and
pre-clinical trials, including its plan initiate a Phase 1 clinical
trial for ALN-PCS, and its expectations regarding reporting data from
its clinical trials for ALN-PCS and ALN-TTR01, 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, the pre-clinical and clinical results for its
product candidates, including ALN-PCS and ALN-TTR01, which may not
support further development of such product candidates, Alnylam's
ability to successfully demonstrate the efficacy and safety of its drug
candidates, including ALN-PCS and ALN-TTR01, in human clinical trials,
and its ability to establish and maintain strategic business alliances
and new business initiatives, as well as those risks more fully
discussed in the "Risk Factors" section of its most recent quarterly
report on Form 10-Q on file with the Securities and Exchange Commission.
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 does not assume any obligation to
update any forward-looking statements.
SOURCE: Alnylam Pharmaceuticals, Inc.
Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
Senior Director, Investor Relations and Corporate Communications
Amanda Sellers, 202-955-6222 x2597