The Medicines Company Presents Clinical Data Analyses for Inclisiran at 87th European Atherosclerosis Society Congress
- Inclisiran administration led to consistent LDL-C reductions, with no
dose adjustment required regardless of renal function, in a combined
analysis of ORION-1 and ORION-7 studies - Late-breaking abstract presentation of ORION-2 study showed that
inclisiran significantly lowered LDL-C without need to increase dose
in homozygous familial hypercholesterolemia - Pivotal Phase 3 data readouts for inclisiran expected in 3Q-2019
followed by regulatory filings expected in the U.S. in 4Q-2019 and
Europe in 1Q-2020
MAASTRICHT, Netherlands–(BUSINESS WIRE)–lt;a href=”https://twitter.com/search?q=%24MDCO&src=ctag” target=”_blank”gt;$MDCOlt;/agt; lt;a href=”https://twitter.com/hashtag/CardioTwitter?src=hash” target=”_blank”gt;#CardioTwitterlt;/agt;–The Medicines Company (NASDAQ: MDCO) today announced presentation of
analyses of two clinical studies of inclisiran at the 87th
European Atherosclerosis Society (EAS) Congress in Maastricht,
Netherlands. A combined analysis (N=279) from the Phase 2 ORION-1 and
Phase 1 ORION-7 trials, presented during an e-poster session,
demonstrated that patients across a range of renal function levels
achieved consistent reductions in low-density lipoprotein cholesterol
(LDL-C) with no dose adjustment necessary for patients with renal
impairment. Results from the Phase 2 ORION-2 pilot study, presented as a
late-breaking abstract, showed that inclisiran provided durable
reductions in LDL-C levels up to day 180 in patients with homozygous
familial hypercholesterolemia (HoFH), a genetic disorder characterized
by very high levels of LDL-C and early onset of cardiovascular disease,
without the need to increase the dose of inclisiran.
“The information discussed at EAS supports inclisiran’s potential to
address the high burden of cardiovascular disease caused by cumulative
exposure to elevated LDL-C,” said Peter Wijngaard, Ph.D., Chief
Development Officer of The Medicines Company. “We are pleased with these
findings that demonstrate inclisiran’s potent, durable and consistent
lowering of LDL-C, as well as favorable tolerability and safety, in
patients with renal insufficiency or HoFH.”
Inclisiran, the first cholesterol-lowering therapy in the siRNA class,
is The Medicines Company’s investigational therapy in Phase 3 clinical
development to evaluate its ability to lower LDL-C through twice-a-year
dosing. The company expects pivotal Phase 3 data readouts for inclisiran
in the third quarter of 2019 followed by anticipated regulatory filings
in the U.S. in the fourth quarter of 2019 and in Europe in the first
quarter of 2020.
“There remains significant unmet need in the treatment of ASCVD, as
approximately four out of five statin-treated patients are not at LDL-C
goals, with poor adherence to therapy a major underlying cause,” said
Mark Timney, Chief Executive Officer of The Medicines Company. “We are
excited at the prospect of bringing forward a revolutionary approach to
treat cardiovascular disease using a twice-a-year therapy with unique
potential to address the need for additional LDL-C lowering and
long-standing medication adherence challenges faced by millions of
people.”
ORION-1 and ORION-7
The aim of the combined analysis of data from ORION-1 and ORION-7 was to
determine whether dose adjustment of inclisiran was necessary for
patients with impaired renal function. Therefore, the objectives were to
evaluate the pharmacokinetics and pharmacodynamics in patients across a
range of renal function levels and to assess the relationship between
estimated glomerular filtration rate (eGFR, a measure of renal function)
and adverse events.
The analysis demonstrated that patients who received inclisiran sodium
300 mg achieved consistent reductions in LDL-C and proprotein convertase
subtilisin-kexin type 9 (PCSK9) regardless of renal status at study
entry. Among all patients in the analysis, treatment-emergent adverse
event rates were not influenced by renal impairment and were not
different from placebo. There was no relationship between inclisiran
administration and eGFR levels, including no exacerbation of renal
impairment. No dose adjustment of inclisiran was required for patients
with renal impairment (mild, moderate or severe).
ORION-1 (N=501) is a Phase 2, placebo-controlled, double-blind,
randomized trial to evaluate the efficacy, safety, and tolerability of
inclisiran in participants with atherosclerotic cardiovascular disease
(ASCVD) or ASCVD-risk equivalents and elevated LDL-C despite maximum
tolerated dose of LDL-C lowering therapies. The trial compares the
effect of different doses of inclisiran and evaluates the potential for
an infrequent dosing regimen. The primary endpoint of the trial is the
percentage change in LDL-C from baseline to day 180. A sub-group
analysis was performed to evaluate long-term pharmacodynamics and safety
of a single-dose (N=60) or two doses (N=59) of inclisiran sodium 300 mg
in subjects with normal renal function or with mild or moderate renal
impairment.
ORION-7 (N=31) is a Phase 1, single-dose, open-label trial to evaluate
the effects of a single dose of inclisiran sodium 300 mg in participants
with mild, moderate and severe renal impairment compared to participants
with normal renal function. The primary endpoint is to determine the
pharmacokinetic and pharmacodynamic parameters, as well as safety, of
inclisiran in subjects with normal and impaired renal function at 48
hours post-dose. Secondary endpoints include changes from baseline in
lipids and lipoproteins, as well as PCSK9, to day 60.
Data from the combined analysis of ORION-1 and ORION-7 were presented on
May 27 during an e-poster session at the 87th EAS Congress
(abstract #EAS19-0576, Efficacy, Safety and Pharmacokinetics of
Inclisiran by Renal Function, Kallend et al).
ORION-2
ORION-2 results presented at EAS showed that HoFH patients (N=4) who
received inclisiran sodium 300 mg met the primary efficacy endpoint of
durable LDL-C lowering up to day 180 and all patients achieved
reductions in PCSK9 and apolipoprotein B. The effects were similar to
those of anti-PCSK9 monoclonal antibody medicines in this patient
population, but without the need to increase the treatment dose.
Secondary endpoints of reductions in PCSK9 and apolipoprotein B from
baseline to day 90 and day 180 were also achieved. Inclisiran was
reported to be well-tolerated, with no drug-related adverse events. A
larger Phase 3 study of inclisiran in HoFH (ORION-5) is ongoing.
ORION-2 (N=4) is a Phase 2 pilot study to assess the safety,
tolerability and efficacy a single dose of inclisiran sodium 300 mg in
participants with genetically confirmed HoFH. The primary endpoint is
percentage change in LDL-C from baseline to day 90 and day 180.
Data from ORION-2 were presented on May 27 during a late-breaking
abstract session at the 87th EAS Congress (abstract
#EAS19-1122, Inclisiran Durability Lowers LDL-C and PCSK9 Expression in
Subjects with Homozygous Familial Hypercholesterolaemia: The ORION-2
Pilot Study, Raal et al).
About Inclisiran
Inclisiran, the first cholesterol-lowering therapy in the siRNA class,
is The Medicines Company’s investigational therapy in Phase 3 clinical
development to evaluate its ability to lower low-density lipoprotein
cholesterol (also known as LDL-C or bad cholesterol) through
twice-a-year dosing. As a siRNA, inclisiran directly targets messenger
RNA and harnesses one of the body’s powerful natural mechanisms, RNA
interference, to prevent production of the PCSK9 protein at its source
in the liver and facilitate removal of LDL-C from the bloodstream. In
Phase 2 studies, inclisiran provided clinically significant LDL-C
reductions greater than 50 percent in addition to the effects of statins
and/or ezetimibe, and LDL-C reductions were sustained throughout the
six-month dosing interval. Inclisiran is not yet approved for use by the
FDA or any other regulatory authority. The Medicines Company obtained
global rights to develop, manufacture and commercialize inclisiran under
a license and collaboration agreement with Alnylam Pharmaceuticals.
Commercial Opportunity
In the U.S. alone, approximately 15.1 million people are
currently treated with lipid-lowering therapies to manage cardiovascular
risk. Approximately 80 percent of high-risk ASCVD patients are not
achieving LDL-C treatment goals with current therapies, and up to
two-thirds of patients do not adhere to available first-line
cholesterol-lowering treatments after one year. This implies a
population of at least 12.7 million Americans who could potentially
benefit from the investigational candidate inclisiran, the first
cholesterol-lowering siRNA with the potential to deliver potent, durable
and consistent lowering of LDL-C levels via twice-a-year dosing that can
help address two critical unmet needs – additional LDL-C lowering and
poor adherence to therapy.
About The Medicines Company
The Medicines Company is a biopharmaceutical company with a singular,
relentless focus on addressing the greatest global healthcare challenge
and burden today – cardiovascular disease. Our purpose is to halt the
deadly progression of atherosclerosis and the cardiovascular risk
created by high levels of LDL-C, or bad cholesterol. The Company is
headquartered in Parsippany, New Jersey. For more information, please
visit www.themedicinescompany.com
and follow us on Twitter @MDCONews
and LinkedIn.
Forward-Looking Statements
Statements contained in this news 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,” “plans,” “expects,” “should,” and
“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 the ability of the Company to
effectively develop inclisiran; whether inclisiran will advance in the
clinical trials process on a timely basis or at all, or succeed in
achieving its specified endpoints; whether the Company will make
regulatory submissions for inclisiran on a timely basis; 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 (SEC), including, without limitation, the risk
factors detailed in the Company’s Quarterly Report on Form 10-Q filed
with the SEC on April 26, 2019, which are incorporated herein by
reference. The Company specifically disclaims any obligation to update
these forward-looking statements.
Contacts
Investor Relations
Krishna Gorti, M.D.
Vice President,
Investor Relations
973 290 6122
krishna.gorti@themedco.com
Media Inquiries
Michael Blash
Vice President,
Communications
973 290 6100
michael.blash@themedco.com
Thank you for donating to DutchNews.nl.
We could not provide the Dutch News service, and keep it free of charge, without the generous support of our readers. Your donations allow us to report on issues you tell us matter, and provide you with a summary of the most important Dutch news each day.
Make a donation