New Long-Term Data Show that Twice-a-Year Dosing with Inclisiran Results in Persistent Lowering of LDL Cholesterol with No Material Safety Observations Out to Three Years

May 18, 2019 Off By BusinessWire
  • Interim results from ongoing ORION-3 study demonstrated sustained
    lowering of LDL-C by more than 50 percent, with time-averaged absolute
    reductions of 59.4 mg/dL
  • No material safety issues observed in the study
  • Pivotal Phase 3 readouts for inclisiran expected in 3Q-2019 followed
    by regulatory filings expected in the U.S. in 4Q-2019 and Europe in

MIAMI–(BUSINESS WIRE)–lt;a href="" target="_blank"gt;$MDCOlt;/agt; lt;a href="" target="_blank"gt;#cholesterollt;/agt;–The Medicines Company (NASDAQ: MDCO) today announced interim results
from the ongoing ORION-3 open-label extension study (Group 1, n=290)
which showed that twice-a-year dosing with inclisiran sodium 300 mg
resulted in consistent lowering of low density lipoprotein cholesterol
(LDL-C) by more than 50 percent with overall follow-up of up to three
years. Inclisiran was well tolerated, and no material safety issues were
observed in the study. These results were presented today during a
late-breaking clinical trial session at the National Lipid Association
(NLA) Scientific Sessions in Miami.

Inclisiran, the first cholesterol-lowering therapy in the siRNA class,
is in Phase 3 clinical development to evaluate its ability to lower
LDL-C through twice-a-year dosing. Pivotal Phase 3 readouts for
inclisiran are expected in the third quarter. ORION-3 (n=382) is an
open-label extension study of the Phase 2 ORION-1 trial to assess the
efficacy, safety and tolerability of long-term dosing of inclisiran.

“The cumulative effects of elevated LDL-C over time continue to place
millions of people with atherosclerosis at increased cardiovascular
risk, despite the widespread use of LDL cholesterol-lowering
treatments,” said John J.P. Kastelein, M.D., Ph.D., ORION-3 study chair
and Professor of Medicine at the Department of Vascular Medicine at the
Academic Medical Center of the University of Amsterdam, The Netherlands.
“These new data from ORION-3 provide further evidence of inclisiran’s
unprecedented ability to deliver persistent LDL-C reductions over a
prolonged period, which can help more patients reliably achieve LDL-C
goals. Inclisiran also demonstrated a favorable safety profile, an
important consideration given the long duration of LDL-C treatment.”

In this interim analysis of ORION-3, inclisiran demonstrated a 51
percent (64.0 mg/dL, p<0.001) reduction in LDL-C levels through day 210,
which was the study’s primary endpoint. The time-averaged absolute LDL-C
reduction with inclisiran was 59.4 mg/dL (p<0.001). These effects were
independent of dose level and number of doses of inclisiran previously
given in the ORION-1 study.

With overall follow-up of approximately three years from the first dose
in ORION-1, no change in the overall safety profile was observed in this
interim analysis of ORION-3 compared to the one-year follow-up in
ORION-1. Inclisiran was well tolerated and no material safety issues
were observed, including no elevations of liver enzymes or changes in
renal function considered related to study medication. Clinically
relevant injection site reactions were infrequent, mild or moderate, and
transient, in line with observations in ORION-1.

“The strong data from ORION-3 bolster our confidence in inclisiran’s
robust therapeutic profile which offers a vastly different value
proposition compared to any other LDL-C lowering option,” said Mark
Timney, Chief Executive Officer of The Medicines Company. “We truly
believe that inclisiran could be a game-changer in cardiovascular care,
providing simplicity and confidence to the treating physician and the
treated patient that LDL cholesterol is lowered.”

“These new results reinforce that the potent, durable and consistent
LDL-lowering effects of inclisiran continue over the long term with
twice-a-year dosing that we believe can address the challenges of
treatment adherence through improved therapeutic coverage and
persistence,” said Peter Wijngaard, Ph.D., Chief Development Officer of
The Medicines Company. “We also remain encouraged by inclisiran’s safety

More than 3,000 patient-years of inclisiran safety data have been
accumulated to date in the ORION program. The data from ORION-3, as well
as ongoing review of blinded data to date from the Phase 3 trials, show
no material safety issues; data are at least as favorable as those
generated and published from the ORION-1 Phase 2 trial.

Background on ORION-1 and ORION-3

ORION-1 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.

Subjects who completed ORION-1 and met all inclusion and exclusion
criteria enrolled into ORION-3 in two groups. In Group 1, subjects
(n=290) previously treated with any inclisiran dose in ORION-1 received
twice-a-year injections of inclisiran sodium 300 mg. The ORION-3 primary
endpoint was mean percent change in LDL-C from the ORION-1 baseline
value, measured at day 210 in Group 1. The interim analysis of ORION-3
presented on May 18, 2019, reported safety and efficacy of inclisiran
for Group 1 only (NLA Scientific Sessions, “Long-term twice-a-year
dosing of inclisiran, a novel siRNA therapy, results in persistent LDL-C
lowering in Phase II extension study (ORION-3),” speaker: John J. P.
Kastelein, M.D., Ph.D.).

In Group 2, subjects (n=92) previously treated with placebo in ORION-1
received one year of treatment with evolocumab (140 mg injections every
two weeks) followed by three years of treatment with inclisiran sodium
300 mg given on day 360 and 450 and every six months thereafter. For
Group 2, safety and efficacy of switching from evolocumab to inclisiran
will be assessed in an exploratory manner. Follow up for Group 2 is
ongoing, and completion is projected to occur in 2022 followed by
anticipated presentation of data in a scientific forum.

Investor Conference Call and Webcast Information

The Company will host a conference call and webcast today at 5:30 p.m.,
U.S. Eastern Standard Time. During the call, the Company’s management
and clinical trial investigators will discuss interim results from the
ongoing ORION-3 study. The dial-in information to access the call is as
follows immediately below. A live audio webcast of the conference call
may be accessed in the “Investors
& Media” section of The Medicines Company

U.S./Canada: (877) 407-0312
International: (201) 389-0899
ID: 13690839

A taped replay of the conference call will be available for
approximately one week. The replay may be accessed as follows
immediately below. An archived webcast will be available after the call

U.S./Canada: (877) 660-6853
International: (201) 612-7415
ID: 13690839

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, but only one out of five (or 2.4 million) is successfully
reaching LDL-C targets with current therapies. 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.

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
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; the extent of the commercial success of
inclisiran, if approved; the strength, durability and life of the
Company’s patent protection for inclisiran and whether the Company will
be successful in extending exclusivity; 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.


Investor Relations
Krishna Gorti, M.D.
Vice President,
Investor Relations
973 290 6122
[email protected]

Media Inquiries
Michael Blash
Vice President,
973 290 6100
[email protected]