—Study meets all interim analysis
goals—
—A single injection of inclisiran (300
mg) lowered ‘bad cholesterol’ (LDL-C) by an average of 51%, and up
to 76%—
—Two injections of inclisiran (300 mg)
lowered LDL-C by an average of 57% and up to 81%—
—Significant LDL-C reductions were
sustained out to 180 days following a single dose—
—Potential for highly-differentiated,
infrequent, low volume dosing regimen of 2 or 3 injections per year
affirmed—
—Inclisiran demonstrated highly encouraging
safety and tolerability—
—Based on the strength of the ORION-1 data, The
Medicines Company expects to advance inclisiran aggressively in a
global Phase 3 development program—
—Conference call to be held at 3:00 p.m.,
Eastern Time, today—
The Medicines Company (Nasdaq:MDCO) and Alnylam Pharmaceuticals,
Inc. (Nasdaq:ALNY) today announced positive results from the
analysis of Day 90 data for 497 patients, as well as analysis of
preliminary Day 180 data for 189 patients, enrolled in the ORION -1
Phase 2 study of inclisiran. Data from ORION-1 were presented today
in a Late-Breaking Clinical Trials session at the American Heart
Association Scientific Sessions 2016 in New Orleans.
Inclisiran (formerly known as PCSK9si or ALN-PCSsc) is an
investigational GalNAc-conjugated RNAi therapeutic targeting
PCSK9—a genetically validated protein regulator of LDL receptor
metabolism—being developed for the treatment of
hypercholesterolemia.
Inclisiran was generally well tolerated and no material safety
issue was observed, including no elevations of liver enzymes
considered related to study medication and no neuropathy or change
in renal function. Overall incidence of treatment emergent adverse
events was 54% both in patients randomized to placebo and in
patients randomized to inclisiran, with no differences between
inclisiran doses. Injection site reactions (ISRs) with inclisiran
were infrequent (observed in 3.2% of patients), mild or moderate,
and transient - in only 2.4% of patients, the reported ISR started
or was still present 4 or more hours after dosing.
Baseline LDL-C was approximately 130 mg/dL among 497 randomized
and treated patients. Among these patients, one 300 mg subcutaneous
injection of inclisiran achieved mean LDL-C reductions of 51% at
Day 60, which were durable to Day 90 (mean 45% and up to 76%). All
differences relative to placebo in these 497 patients were
statistically significant (p <0.0001).
Among 189 randomized and treated patients who had been followed
for 180 days or more by the interim data cut-off date of October
25, 2016, one 300 mg subcutaneous injection of inclisiran achieved
mean LDL-C reductions of 59% at Day 60, which were durable to Day
90 (mean 50%) and Day 180 (mean 43% and up to 81%). Two 300 mg
injections of inclisiran - one given on Day 1 and one on Day 90 -
achieved a mean LDL-C reduction of 57% at Day 120, which was
durable to Day 180 (mean 52% and up to 81%). All differences
relative to placebo in these 189 patients were statistically
significant (p <0.0001).
"The remarkable strength and consistency of the data from
ORION-1 provide compelling support for the medical and commercial
potential of inclisiran and drive our decision to move into Phase 3
with what we believe could be a highly-competitive and potentially
transformational medicine,” said Clive Meanwell, M.D., Ph.D., Chief
Executive Officer of The Medicines Company. “We will focus our
resources on inclisiran for aggressive Phase 3 development to
ensure that this promising agent is investigated thoroughly and
rapidly in Phase 3, submitted to worldwide regulatory agencies and,
if approved, made available to millions of at-risk, often
non-adherent, patients worldwide who continue to grapple with the
realities and risks of high LDL-C.”
David Kallend, MBBS, Vice President and Global Medical Director
of The Medicines Company, added, “These positive results from
ORION-1 showed robust and durable knockdown of LDL-C and a very
encouraging safety and tolerability profile at this stage of
development. The data strengthen our earlier findings in Phase 1 -
published recently in the New England Journal of Medicine - that an
infrequent, low volume dosing regimen of 2 or 3 injections per year
could constitute a highly-differentiated and competitive treatment
for patients with hypercholesterolemia. Inclisiran also has the
potential to open new care approaches linking the temporal cycle of
LDL-C monitoring with counseling and administration of therapy. The
ORION-1 data have enabled us to select an optimal dose of 300 mg,
and the data presage a quick and efficient transition to Phase 3
development.”
John J.P. Kastelein, M.D., Ph.D., Professor of Medicine and
Chairman of the Department of Vascular Medicine at
the Academic Medical Center (AMC) of the University
of Amsterdam, said, "Elevated LDL-C remains a major risk factor for
coronary artery disease, and new therapies are needed for patients
who are refractory or intolerant to current approaches for
management of their LDL-C levels. PCSK9 therapies have now emerged
as a new class of drugs for treatment of hypercholesterolemia, and
I believe that these agents have the potential to make a meaningful
difference for patients. ORION-1 strengthens prior data with
inclisiran, especially the degree and durability of LDL-C lowering
effects. If the safety and efficacy of this novel investigational
PCSK9 synthesis inhibitor can be confirmed in Phase 3 studies to
support approval, it may offer an important treatment option for
patients, physicians, and payers."
John Maraganore, Ph.D., Chief Executive Officer of Alnylam,
added, “We are delighted with these data from the ORION development
program for inclisiran and thankful for the progress made by
investigators and our partner, The Medicines Company. We are very
excited to see the rapid progression of the program worldwide and
are confident that our RNAi platform provides the opportunity to
create new medicines for important diseases such as
hypercholesterolemia, which have major unmet medical needs.”
Conference Call and Webcast Details
The Medicines Company will host a conference call and webcast
today at 3:00 p.m., Eastern Time.
The dial-in information to access the call is:
U.S./Canada: (877) 359-9508International: (224)
357-2393Conference ID: 1645474
An audio replay will be available commencing approximately two
hours following the conclusion of the call and will be available
for one week. The replay may be accessed as follows:
U.S./Canada: (855) 859-2056International: (404)
537-3406Conference ID: 1645474
A live audio webcast and accompanying slide presentation will be
available in the “Investors” section of The Medicines Company
website. A replay of the webcast will also be available.
About ORION-1
ORION-1 is a placebo-controlled, double-blind, randomized Phase
2 study of single or multiple subcutaneous injections of inclisiran
in a total of 501 patients with atherosclerotic cardiovascular
disease (ASCVD) or ASCVD-risk equivalents (e.g., diabetes and familial hypercholesterolemia)
and elevated LDL-C despite maximum tolerated doses of LDL-C
lowering therapies. The study compares the effect of different
doses of inclisiran and evaluates the potential for an infrequent
dosing regimen. The primary endpoint of the study is the percentage
change in LDL-C from baseline at Day 180.
About Inclisiran
Inclisiran (formerly known as PCSK9si or ALN-PCSsc) is an
investigational GalNAc-conjugated RNAi therapeutic targeting PCSK9
– a genetically validated protein regulator of LDL receptor
metabolism – being developed for the treatment of
hypercholesterolemia. In contrast to anti-PCSK9 monoclonal
antibodies (MAbs) that bind to PCSK9 in blood, inclisiran is a
first-in-class investigational medicine that acts by turning off
PCSK9 synthesis in the liver.
In a previous, single-ascending dose study, inclisiran was
associated with maximal PCSK9 knockdown of 88.7% with mean maximum
knockdown of up to 82.3 ± 2.0% and maximal LDL-C reduction of 78.1%
with mean maximum lowering of up to 59.3 ± 5.0%. At Day 180, a
single dose of inclisiran was associated with an up to 53%
reduction in LDL-C, with a least squares mean percent lowering of
47.0% in the 300 mg dose cohort.
In a previous multiple ascending dose study, inclisiran was
associated with maximal PCSK9 knockdown of 94.4% with mean maximum
knockdown of up to 88.5 ± 1.6% and maximal LDL-C reduction of 83.0%
with mean maximum lowering of up to 64.4 ± 5.4%.
Inclisiran was generally well tolerated following single and
multiple subcutaneous dose administration, with no serious adverse
events or discontinuations due to adverse events.
The Medicines Company and Alnylam Pharmaceuticals, Inc. are
collaborating in the advancement of inclisiran per the companies'
agreement formed in early 2013. Under the terms of the agreement,
Alnylam completed certain pre-clinical studies and the Phase 1
clinical study, with The Medicines Company leading and funding the
development of inclisiran from Phase 2 forward, as well as
potential commercialization.
About The Medicines Company
The Medicines Company is a biopharmaceutical company driven by
an overriding purpose—to save lives, alleviate suffering and
contribute to the economics of healthcare. The Company’s mission is
to create transformational solutions to address the most pressing
healthcare needs facing patients, physicians and providers in three
critical therapeutic areas: serious infectious disease care,
cardiovascular care and surgery and perioperative care. The Company
is headquartered in Parsippany, New Jersey, with global innovation
centers in California and Switzerland.
The Medicines Company Forward Looking Statements
Statements contained in this press release 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," "expects," “potential,” 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 clinical trials for
inclisiran will advance in the clinical process on a timely basis,
or at all, or succeed in achieving their specified endpoints;
whether physicians, patients and other key decision makers will
accept clinical trial results; whether the Company will make
regulatory submissions for inclisiran on a timely basis, or at all;
whether its regulatory submissions will receive approvals from
regulatory agencies on a timely basis, or at all; 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 with the Securities and
Exchange Commission on October 27, 2016, which are incorporated
herein by reference. The Company specifically disclaims any
obligation to update these forward-looking statements.
About Alnylam Pharmaceuticals, Inc.
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. 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 Statements
Various statements in this release concerning Alnylam's future
expectations, plans and prospects, including without limitation,
Alnylam's views with respect to the potential for inclisiran,
including the potential dosing regimen, the timing of clinical
studies and the presentation of clinical data, its expectations
regarding its STAr pipeline growth strategy, and 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 our
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.
The scientific information discussed in this news release
relating to inclisiran is preliminary and investigative. Inclisiran
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 therapeutic.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20161115005596/en/
The Medicines CompanyMediaMeg Langan,
973-290-6319Vice
Presidentmargaret.langan@themedco.comorInvestorsKrishna
Gorti, M.D., 973-290-6122Vice President, Investor
Relationskrishna.gorti@themedco.comorAlnylam
PharmaceuticalsInvestors and MediaChristine Regan
Lindenboom, 617-682-4340Vice
Presidentclindenboom@alnylam.comorInvestorsJosh Brodsky,
617-551-8276Associate Directorjbrodsky@alnylam.com
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