Interim Results from ORION-1 Phase 2 Study of
Inclisiran to be Presented in Late-Breaking Clinical Trial Session
at the American Heart Association Scientific Sessions on November
15, 2016
Alnylam Pharmaceuticals,
Inc. (Nasdaq:ALNY), the leading RNAi therapeutics
company, and The Medicines Company (Nasdaq:MDCO), a leading
biopharmaceutical development and cardiovascular product company,
today announced that results from the Phase 1 study of inclisiran
(in-CLEE-si-ran), the recommended International Nonproprietary Name
(INN) for ALN-PCSsc, were published in The New England Journal of
Medicine (NEJM). Inclisiran is an investigational RNAi therapeutic
targeting PCSK9 – a genetically validated protein regulator of LDL
receptor metabolism – being developed for the treatment of
hypercholesterolemia. The paper can be found online here.
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Results from the study showed doses ≥300 mg (single or multiple
doses) significantly reduced PCSK9 and LDL cholesterol for at least
6 months. Moreover, inclisiran was found to be generally well
tolerated.
"The published findings from our Phase 1 trial with inclisiran
add to the clinical evidence supporting PCSK9 as a therapeutic
target for significantly lowering LDL cholesterol, as well as the
ability of RNAi therapeutic candidates to inhibit synthesis of
liver-derived target proteins in a potent and durable manner,” said
Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of R&D
and Chief Medical Officer of Alnylam. “We believe that inclisiran
represents an innovative and differentiated approach for the
treatment of hypercholesterolemia.”
Inclisiran is currently being studied in the ORION-1 Phase 2
study by The Medicines Company. With more than 500 patients
enrolled, ORION-1 is the largest study of a GalNAc-siRNA conjugate
to date. The Medicines Company recently announced positive top-line
results from the day 90 interim analysis of the Phase 2 study
demonstrating significant and durable LDL-C reduction that
validates the potential for a triannual or biannual dosing regimen.
Top-line results also showed that inclisiran was generally well
tolerated, with no evidence of drug-related elevations of liver
enzymes, neuropathy adverse events, or changes in renal function.
The Medicines Company plans to present complete interim results
from the ongoing study in a Late-Breaking Clinical Trial Session at
the American Heart Association (AHA) Scientific Sessions on
November 15, 2016.
“We look forward to presenting the interim results of the
ORION-1 Phase 2 data at AHA this week including Day 90 follow-up
results for all 501 patients and a preliminary analysis of Day 180
follow-up for up to 200 patients,” said David Kallend, MBBS, Vice
President and Global Medical Director at The Medicines Company.
“Based on the strong results from the Phase 1 study, we hope to
further elucidate the hypothesis of triannual or biannual dosing of
inclisiran with the ORION-1 results.”
The NEJM publication highlights key results from the Phase 1
clinical trial of inclisiran, including safety and pharmacodynamic
measures (PCSK9, LDL cholesterol, exploratory lipid
parameters).
In the single-ascending-dose (SAD) phase, pharmacodynamic
measures showed:
- Doses ≥300 mg reduced PCSK9 at day 84
(up to a least-squares mean (LSM) reduction of 74.5%);
- Doses ≥100 mg reduced LDL cholesterol
at day 84 (up to a LSM reduction of 50.6%);
- Reductions in PCSK9 and LDL cholesterol
were maintained at day 180 with little variation over the 6-month
period for doses ≥300 mg.
In the multiple-dose (MD) phase, pharmacodynamic measures
showed:
- Reduced PCSK9 (up to a LSM reduction of
83.8%) and LDL cholesterol (up to a LSM reduction of 59.7%) at day
84;
- Levels of PCSK9 and LDL cholesterol
remained reduced in all the inclisiran cohorts at day 196.
Safety and side effect profile evaluations showed:
- Inclisiran was generally well tolerated
following single and multiple subcutaneous dose
administration;
- No serious adverse events (SAEs) or
discontinuations due to AEs were reported;
- All observed adverse events (AEs) were
mild or moderate in severity;
- There was one Grade 3 GGT elevation
considered related to statin therapy.
The lead development responsibility for inclisiran transitioned
from Alnylam to The Medicines Company in August 2015. The two
companies are now working to advance inclisiran in the ORION
development program, a comprehensive global clinical development
plan designed to support regulatory approval and market access
worldwide.
About the Inclisiran Phase 1 Study
The Phase 1 trial of inclisiran was conducted in the U.K. as a
randomized, single-blind, placebo-controlled, single ascending- and
multi-dose, subcutaneous dose-escalation study. The study enrolled
69 volunteer subjects with elevated baseline LDL-C (≥ 100 mg/dL),
with subjects randomized 3:1, drug: placebo. The study was
performed in two phases: a single ascending dose (SAD) phase and a
multiple dose (MD) phase. The MD phase also included subjects both
on and off stable doses of statin co-medication. The primary
objective of the Phase 1 study was to evaluate the safety, side
effect profile, and pharmacodynamics effects of inclisiran.
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
adequate LDL-C levels with currently available therapies such as
statins, including genetic familial hypercholesterolemia (FH)
patients, acute coronary syndrome patients, high-risk patient
populations (e.g., patients with coronary artery disease, diabetes,
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 GalNAc Conjugates and Enhanced Stabilization Chemistry
(ESC)-GalNAc Conjugates
GalNAc-siRNA conjugates are a proprietary Alnylam delivery
platform and are designed to achieve targeted delivery of RNAi
therapeutics to hepatocytes through uptake by the
asialoglycoprotein receptor. Alnylam's Enhanced Stabilization
Chemistry (ESC)-GalNAc-conjugate technology enables subcutaneous
dosing with increased potency and durability, and a wide
therapeutic index. This ESC-GalNAc-conjugate delivery platform is
being employed in nearly all of Alnylam's pipeline programs,
including inclisiran and several other programs in clinical
development.
About 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 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. 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.
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.
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.
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version on businesswire.com: http://www.businesswire.com/news/home/20161113005052/en/
Alnylam Pharmaceuticals, Inc.Christine Regan Lindenboom,
617-682-4340(Investors and Media)orJosh Brodsky,
617-551-8276InvestorsorThe Medicines CompanyMedia:Meg
Langan, 973-290-6319Vice
Presidentmargaret.langan@themedco.comorInvestors:Krishna Gorti,
M.D., 973-290-6122Vice President, Investor
RelationsKrishna.Gorti@themedco.com
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