— Top-line efficacy data from the MILANO-PILOT trial, which enrolled
126 patients, provide insufficient basis for further investment by the
Company —
— Discontinuation will enable the Company to reallocate and focus
substantial additional capital onto the development of its PCSK9
synthesis inhibitor —
— Results from the MILANO-PILOT trial will be presented in the
Late-Breaking Clinical Trial Session at American Heart Association
Scientific Sessions 2016 —
PARSIPPANY, N.J.--(BUSINESS WIRE)--Nov. 7, 2016--
The Medicines Company (NASDAQ:MDCO) announced today the immediate
discontinuation of the clinical development program for MDCO-216, its
investigational cholesterol efflux promoter. Data from the
recently-completed MILANO-PILOT trial did not show drug effects on
intracoronary atherosclerotic plaque sufficient to warrant further
development. The safety profile of MDCO-216 was excellent.
Information now available to the Company from the MILANO-PILOT trial of
MDCO-216, when evaluated in light of the evolving treatment landscape
for atherosclerotic cardiovascular disease, including the emergence of
highly-positive data from the ORION-1 trial of the Company’s PSCK9
synthesis inhibitor, drove the Company’s decision to discontinue further
investment in the clinical development of MDCO-216. The Company’s
decisive move will free up substantial additional capital, which will be
reallocated and focused onto the development of its PCSK9 synthesis
inhibitor, which demonstrated significant and durable LDL-C reduction in
the ORION-1 trial — reaffirming a triannual, and potentially biannual,
dosing regimen with high standards of safety and tolerability and a
highly-competitive profile. Results from the ORION-1 trial, including
Day 90 follow-up for all 501 patients, as well as top-line data from a
preliminary analysis of Day 180 follow-up for up to 200 patients, will
be presented in the Late-Breaking Clinical Trial Session at the AHA
Scientific Sessions 2016, on November 15, 2016, in New Orleans.
“We deliberately focused our initial development investment in MDCO-216
on clinical proof of concept. Unfortunately, the efficacy data from
MILANO-PILOT do not support a prudent decision to make the significant,
near-term investment required to move MDCO-216 forward,” stated Clive
Meanwell, M.D., Ph. D., Chief Executive Officer of The Medicines
Company. “In spite of promising earlier research findings, and
impressive progress with manufacturing development and safety, in the
light of these efficacy data and in view of the potentially enormous
opportunity and highly-favorable risk-reward profile presented by our
PSCK9 synthesis inhibitor, we have been decisive in immediately
terminating the MDCO-216 development program. This decision will allow
us to reallocate substantial additional capital to the further
development of our PCSK9 synthesis inhibitor. We are extremely grateful
for the leadership of our lead investigators, Dr. Stephen J. Nicholls,
MBBS, Ph.D., FRACP South Australian Health and Medical Research
Institute, Adelaide, Australia, and Dr. Steven E. Nissen, M.D., Chairman
of Cardiovascular Medicine, Cleveland Clinic, who continue to blaze a
trail in the field with sophisticated and groundbreaking coronary
ultrasound imaging studies. We have ensured that Drs. Nicholls and
Nissen have full access to all data from MILANO-PILOT for analysis,
presentation and publication. We also thank the patients and
collaborators who participated in the MILANO-PILOT trial.”
The Company is supporting the close-out of the MILANO-PILOT trial and
results will be presented by Dr. Nicholls, its principal investigator,
in the Late-Breaking Clinical Trial Session at the American Heart
Association (AHA) Scientific Sessions 2016, on November 15, 2016, in New
Orleans.
The Company is working to ensure that all MILANO-PILOT trial
investigators, regulatory authorities and collaboration partners are
informed of the decision to discontinue further development of MDCO-216.
The Company does not expect to incur any charge associated with the
discontinuation of the MDCO-216 development program.
About MILANO-PILOT
MILANO-PILOT was a proof-of-concept, double-blind, placebo-controlled,
randomized study utilizing IVUS (Intravascular Ultrasound) to measure
the effect of MDCO-216 on atherosclerotic plaque burden and to evaluate
MDCO-216's impact on cholesterol efflux. The study involves 120 patients
with ACS and will likewise assess the safety of weekly 20mg/kg MDCO-216
infusions over a five-week period.
About MDCO-216
MDCO-216, an investigational product not approved for commercial use in
any market, is a complex of dimeric recombinant apolipoprotein A-1
Milano (ApoA-1 Milano) and a phospholipid (POPC) which was under
development to improve cardiovascular outcomes by reducing plaque burden
in patients with atherosclerotic disease. MDCO-216 mimics pre-beta HDL
and induces cholesterol efflux, which is the first step in the reverse
cholesterol transport, a process of removal of deposited cholesterol
from vessel walls and therefore has a potential to reduce plaque burden
in patients with coronary artery disease. ApoA-1 Milano is a protein
discovered in residents of a Northern Italian village who remarkably
have little atherosclerotic build-up despite exceptionally low levels of
cardioprotective HDL in combination with elevated levels of harmful
triglycerides.
About ORION-1
ORION-1 is a placebo-controlled, double-blind, randomized Phase II trial
of single or multiple subcutaneous injections of PCSK9si 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 trial compares the effect of different
doses of PCSK9si 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 PCSK9si
PCSK9si (also known as 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, PCSK9si is a
first-in-class investigational medicine that acts by turning off PCSK9
synthesis in the liver.
In a previous, single-ascending dose study, PCSK9si was associated with
maximal PCSK9 knockdown of 88.7 percent with mean maximum knockdown of
up to 82.3 ± 2.0 percent and maximal LDL-C reduction of 78.1 percent
with mean maximum lowering of up to 59.3 ± 5.0 percent. At Day 180, a
single dose of PCSK9si was associated with an up to 53 percent reduction
in LDL-C, with a least squares mean percent lowering of 47.0 percent in
the 300 mg dose cohort.
In a previous multiple ascending dose study, PCSK9si was associated with
maximal PCSK9 knockdown of 94.4 percent with mean maximum knockdown of
up to 88.5 ± 1.6 percent and maximal LDL-C reduction of 83.0 percent
with mean maximum lowering of up to 64.4 ± 5.4 percent.
PCSK9si 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 are collaborating in
the advancement of PCSK9si 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 PCSK9si 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.
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 our product candidates, including
PCSK9si and MDCO-216, 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 its product candidates 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.
View source version on businesswire.com: http://www.businesswire.com/news/home/20161107006553/en/
Source: The Medicines Company
The Medicines Company
Media:
Meg
Langan, 973-290-6319
Vice President
margaret.langan@themedco.com
or
Investor
Relations:
Krishna Gorti, M.D., 973-290-6122
Vice
President, Investor Relations
Krishna.Gorti@themedco.com
