The Medicines Company and Alnylam Form Strategic Alliance to Develop and Commercialize RNAi Therapeutics Targeting PCSK9 for the Treatment of Hypercholesterolemia
Feb 04, 2013
- The Medicines Company Obtains Exclusive Global License to Advance
ALN-PCS RNAi Therapeutic Program -
- Alnylam to Receive $25 Million in Upfront Payment in Addition to
Milestone Payments and Royalties on Product Sales -
- Companies to Host Conference Call Today at 8:30 a.m. ET to Discuss
Collaboration -
PARSIPPANY, N.J. & CAMBRIDGE, Mass.--(BUSINESS WIRE)--
The
Medicines Company (Nasdaq: MDCO) and Alnylam
Pharmaceuticals, Inc. (Nasdaq: ALNY), a
leading RNAi therapeutics company, announced today that they have formed
an exclusive global alliance for the development and commercialization
of Alnylam's ALN-PCS RNAi therapeutic program for the treatment of
hypercholesterolemia.
"This new alliance unites two organizations with a shared culture and
commitment to innovation. In my view and past experience, there could be
no stronger partner for our ALN-PCS program than The Medicines Company,
which has demonstrated industry-wide leadership in the advancement of
cardiovascular medicines to patients and remarkable success in its
strategy of in-licensing, developing, and commercializing breakthrough
products," said John Maraganore, Ph.D., Chief Executive Officer of
Alnylam. "For Alnylam, this new partnership enables the advancement of
ALN-PCS, an important program within our ‘Alnylam 5x15' product
development and commercialization strategy focused on RNAi therapeutics
directed toward genetically validated targets. We believe that the
ALN-PCS program holds great promise for the development of a significant
therapeutic option for patients with hypercholesterolemia, and that the
unique mechanism of action for ALN-PCS could provide a differentiated
and potentially best-in-class strategy for PCSK9 antagonism."
"Our focus on acute and intensive care medicine has led us to a
leadership position with Angiomax® (bivalirudin) and potentially with
cangrelor in the management of patients in extreme risk as a consequence
of the rupture of their vulnerable coronary artery plaque at and around
the time of acute coronary syndromes. Meantime, we have made progress
with MDCO-216 (ApoA-1 Milano), a turbocharged form of HDL-C (‘good
cholesterol') which has the potential to modify disease through reverse
cholesterol transport," said Clive Meanwell, M.D., Ph.D., Chairman and
Chief Executive Officer of The Medicines Company. "Now, this exciting
collaboration with Alnylam - leaders in their field of RNAi - adds a
second potentially disease modifying approach and more cutting edge
technology to our portfolio. We have seen that PCSK9 gene silencing can
substantially reduce LDL-cholesterol in patients and has epidemiological
and disease mechanisms studies suggest this can further reduce the risks
of the world's number one killer, coronary artery disease. Clearly we
see the complementarity of approaches which increase ‘good cholesterol'
(HDL-C) and decrease ‘bad cholesterol' (LDL-C). We look forward to
working with our colleagues at Alnylam for whom we have the greatest
respect and admiration based upon earlier collaborations particularly
around Angiomax, which was invented by John Maraganore."
PCSK9 (proprotein convertase subtilisin/kexin type 9) is a protein that
regulates low-density lipoprotein (LDL) receptor levels on hepatocytes;
gain-of-function human mutations in PCSK9 are associated with
hypercholesterolemia while loss-of-function mutations are associated
with lower levels of LDL cholesterol and a reduced risk of
cardiovascular disease. ALN-PCS is a PCSK9 synthesis inhibitor that
reduces intracellular and extracellular levels of PCSK9 resulting in
lowered plasma levels of LDL-C. MDCO-216 is a naturally occurring
variant of a protein found in high-density lipoprotein, or HDL. It is a
reverse cholesterol transport agent designed to reduce atherosclerotic
plaque burden development and thereby reduce the risk of adverse
thrombotic events.
Under this alliance, The Medicines Company and Alnylam intend to
collaborate on the advancement of the ALN-PCS program. Alnylam's ALN-PCS
program includes ALN-PCS02 - an intravenously administered RNAi
therapeutic which has completed a Phase I trial, and ALN-PCSsc - a
subcutaneously administered RNAi therapeutic currently in pre-clinical
development. Alnylam will continue the program for an estimated one to
two years to complete certain pre-clinical and Phase I clinical studies.
The Medicines Company is responsible for leading and funding development
from Phase II forward and commercializing the ALN-PCS program if
successful. Under the terms of the agreement, The Medicines Company will
make an upfront cash payment of $25 million to Alnylam. Alnylam may also
receive potential development and commercial milestone payments of up to
$180 million. Alnylam will be eligible to receive scaled double-digit
royalties on global products sales of ALN-PCS products.
Alnylam has completed a Phase I trial of ALN-PCS02 in healthy volunteer
subjects with elevated baseline LDL-C. Results
showed that administration of a single intravenous dose of drug, in the
absence of concomitant lipid-lowering agents such as statins, resulted
in statistically significant and durable reductions of PCSK9 plasma
levels of up to 84% and lowering of LDL-C of up to 50%. ALN-PCS02 was
shown to be generally safe and well tolerated in this study and there
were no serious adverse events related to study drug administration.
Alnylam has also presented
pre-clinical data from its ALN-PCSsc program demonstrating potent
knockdown of the PCSK9 target gene with an ED50 of less than
0.3 mg/kg after a single subcutaneous dose.
"Cardiovascular disease remains the leading cause of mortality
worldwide, with elevated LDL-C a major modifiable risk factor. New
strategies are needed to dramatically and rapidly reduce LDL-C and
prevent acute cardiovascular events that result from the rupture of
cholesterol rich plaque when patients are at their most vulnerable,"
said Daniel J. Rader, M.D., professor of Medicine and chief, Division of
Translational Medicine and Human Genetics, at the Perelman School of
Medicine at the University of Pennsylvania. "As a key regulator of the
LDL receptor, liver-expressed PCSK9 is one of the most important and
best validated new targets in molecular medicine for the treatment of
hypercholesterolemia. The ALN-PCS data generated to date are very
encouraging and I look forward to continued clinical studies that
highlight the unique mechanistic approach of PCSK9 synthesis inhibitors."
Dr. Rader serves as a member of Alnylam's Scientific Advisory Board and
as a consultant on Alnylam's ALN-PCS program, and Alnylam and Dr. Rader
collaborate on research for which Alnylam provides materials.
Conference Call Information
The Medicines Company and Alnylam will host a conference call today at
8:30 a.m. ET to discuss this new collaboration. 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 96998933. A
replay of the call will be available beginning at 11:30 a.m. ET. To
access the replay, please dial 855-859-2056 (domestic) or 404-537-3406
(international) and refer to conference ID 96998933. A live audio
webcast of the presentation will be available on The Medicines Company
website at www.themedicinescompany.com,
and on the News & Investors section of the Alnylam's website, www.alnylam.com
About Hypercholesterolemia
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. Some forms of
hypercholesterolemia can be treated through dietary restrictions,
lifestyle modifications (e.g., exercise and smoking cessation) and
medicines such as statins. However, a large proportion of patients with
hypercholesterolemia are not achieving target LDL-C goals with statin
therapy, including genetic familial hypercholesterolemia patients, acute
coronary syndrome patients, high-risk patient populations (e.g.,
patients with coronary artery disease, diabetics, symptomatic carotid
artery disease, etc.) and other patients that are statin intolerant.
Severe forms of hypercholesterolemia are estimated to affect more than
500,000 patients worldwide, and as a result, there is a significant need
for novel therapeutics to treat patients with hypercholesterolemia whose
disease is inadequately managed by existing therapies.
About ALN-PCS
ALN-PCS is a systemically delivered RNAi therapeutic targeting the gene
proprotein convertase subtilisin/kexin type 9 (PCSK9), a target
validated by human genetics that is involved in the metabolism of
low-density lipoprotein cholesterol (LDL-C, or "bad" cholesterol).
ALN-PCS therapies are PCSK9 synthesis inhibitors that lower levels of
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). PCSK9 synthesis inhibition through an
RNAi mechanism has the potential to lower tissue and circulating plasma
PCSK9 protein levels resulting in higher LDL receptor levels in the
liver, and subsequently lower LDL-C levels in the blood stream. Lower
LDL-C is associated with a decreased risk of cardiovascular disease,
including myocardial infarction and stroke.
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 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 The Medicines Company
The Medicines Company (Nasdaq: MDCO) provides medical solutions to
improve health outcomes for patients in acute and intensive care
hospitals worldwide. These solutions comprise medicines and knowledge
that directly impact the survival and well being of critically ill
patients.
The Medicines Company Forward-Looking Statement
Statements contained in this press release about The Medicines Company
that are not purely historical, and all other statements that are not
purely historical, may be deemed to be forward-looking statements for
purposes of the safe harbor provisions under The Private Securities
Litigation Reform Act of 1995. Without limiting the foregoing, the words
"believes," "anticipates" and "expects" and similar expressions are
intended to identify forward-looking statements. These forward-looking
statements involve known and unknown risks and uncertainties that may
cause the Company's actual results, levels of activity, performance or
achievements to be materially different from those expressed or implied
by these forward-looking statements. Important factors that may cause or
contribute to such differences include whether the Company's products
will advance in the clinical trials process on a timely basis or at all,
whether the Company will make regulatory submissions for product
candidates on a timely basis, whether its regulatory submissions will
receive approvals from regulatory agencies on a timely basis or at all,
whether physicians, patients and other key decision makers will accept
clinical trial results, and such other factors as are set forth in the
risk factors detailed from time to time in the Company's periodic
reports and registration statements filed with the Securities and
Exchange Commission including, without limitation, the risk factors
detailed in the Company's Quarterly Report on Form 10-Q filed on
November 9, 2012, which are incorporated herein by reference. The
Company specifically disclaims any obligation to update these
forward-looking statements.
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-AT3 for the treatment of hemophilia and rare
bleeding disorders (RBD), ALN-AS1 for the treatment of acute
intermittent porphyria (AIP), ALN-PCS for the treatment of
hypercholesterolemia, and ALN-TMP for the treatment of
hemoglobinopathies. As part of its "Alnylam 5x15TM" strategy,
the company expects to have five RNAi therapeutic products for
genetically defined diseases in clinical development, including programs
in advanced stages, on its own or with a partner by the end of 2015.
Alnylam has additional partnered programs in clinical or development
stages, including ALN-RSV01 for the treatment of respiratory syncytial
virus (RSV) infection and ALN-VSP for the treatment of liver cancers.
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, Cubist, Ascletis, Monsanto, Genzyme, and The Medicines
Company. In addition, Alnylam holds a significant equity position in
Regulus Therapeutics Inc., a company focused on discovery, development,
and commercialization of microRNA therapeutics. Alnylam has also formed
Alnylam Biotherapeutics, a division of the company focused on the
development of RNAi technologies for applications in biologics
manufacturing, including recombinant proteins and monoclonal antibodies.
Alnylam's VaxiRNA™ platform applies RNAi technology to improve the
manufacturing processes for vaccines; GlaxoSmithKline is a collaborator
in this effort. 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.
About "Alnylam 5x15™"
The "Alnylam 5x15" strategy, launched in January 2011, establishes a
path for development and commercialization of novel RNAi therapeutics
directed toward genetically defined targets for 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.
By the end of 2015, the company expects to have five such RNAi
therapeutic programs in clinical development, including programs in
advanced stages, on its own or with a partner. The "Alnylam 5x15"
programs include ALN-TTR for the treatment of transthyretin-mediated
amyloidosis (ATTR), ALN-AT3 for the treatment of hemophilia and rare
bleeding disorders (RBD), ALN-AS1 for the treatment of acute
intermittent porphyria (AIP), ALN-PCS for the treatment of
hypercholesterolemia, ALN-TMP for the treatment of hemoglobinopathies,
and other programs. Alnylam intends to focus on developing and
commercializing certain programs from this product strategy itself in
North and South America, Europe, and other parts of the world; these
include ALN-TTR, ALN-AT3, and ALN-AS1; the company will seek global
development and commercial alliances for other programs.
Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam's future
expectations, plans and prospects, including without limitation,
statements regarding Alnylam's views with respect to the potential for
RNAi therapeutics, including the potential for the ALN-PCS program,
including ALN-PCS02 and ALN-PCSsc, its expectations regarding the
receipt of upfront and potential development and commercialization
milestones and royalty payments on worldwide net sales, if any, under
The Medicines Company agreement, and Alnylam's expectations regarding
its "Alnylam 5x15" product strategy, 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 successfully demonstrate the efficacy
and safety of its drug candidates and the pre-clinical and clinical
results for these product candidates, including ALN-PCS02 and ALN-PCSsc,
which may not support further development of such product candidates,
both our and The Medicines Company's ability to successfully advance
ALN-PCS02 and/or ALN-PCSsc resulting in the potential payment of
milestones and royalties to us, actions of regulatory agencies, which
may affect the initiation, timing and progress of clinical trials for
such product candidates, obtaining, maintaining and protecting
intellectual property, obtaining regulatory approval for products,
competition from others using technology similar to Alnylam's and others
developing products for similar uses, and Alnylam's ability to establish
and maintain strategic business alliances, including its collaboration
with The Medicines Company, and new business initiatives, as well as
those risks more fully discussed in the "Risk Factors" filed with
Alnylam's current report on Form 8-K filed with the Securities and
Exchange Commission (SEC) on January 14, 2013 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 does not
assume any obligation to update any forward-looking statements.
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The Medicines Company
Michael Mitchell, 973-290-6097
Head
of Global Communications
michael.mitchell@themedco.com
or
Alnylam
Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
Vice
President, Investor Relations and
Corporate Communications
or
Spectrum
Amanda
Sellers (Media), 202-955-6222 x2597
Source: Alnylam Pharmaceuticals, Inc.
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