—Trial stopped early following recommendation
by independent Data Safety and Monitoring Board—
—Meropenem-vaborbactam demonstrated improved
clinical cure rates across all infection types and reduced rate of
renal adverse events compared to best available therapy—
—The Company also announces VabomereTM as the
U.S. and European trade name for meropenem-vaborbactam—
The Medicines Company (NASDAQ:MDCO) today announced positive
results from an interim analysis of the TANGO-2 trial of its
fixed-dose, investigational antibiotic combination,
meropenem-vaborbactam. Randomization in the trial was stopped
early, following a recommendation by the TANGO-2 independent Data
and Safety Monitoring Board (DSMB) based on an analysis of 72
patients, including 43 patients with microbiologically evaluable
carbapenem-resistant Enterobacteriaceae (CRE) infections of blood,
lung, urinary tract and abdominal organs. The DSMB concluded that a
risk-benefit analysis of available data no longer supported
randomization of additional patients to the best available therapy
comparator arm. The Company will continue to enroll patients into
an amended, single-arm study protocol for treatment with
meropenem-vaborbactam at selected sites.
The Company expects that data from the TANGO-2 trial will be
presented at a future medical conference and published in a
peer-reviewed journal.
The Company today also announced that it has selected, and both
U.S. and European regulatory authorities have accepted, VabomereTM
as the U.S. and European trade name for meropenem-vaborbactam,
assuming marketing applications are approved. Previously,
meropenem-vaborbactam was commonly referred to as “Carbavance.”
The DSMB’s recommendation to discontinue randomization into the
TANGO-2 trial was based on the results of an interim analysis of
data from TANGO-2, which showed that, for efficacy,
statistically-significant differences favor meropenem-vaborbactam
over best available therapy for clinical cure at the test of cure
visit in the protocol-specified primary population (all patients
with microbiologically-evaluable CRE). Mortality rates were also
lower among patients treated with meropenem-vaborbactam. The DSMB
also noted a clear difference in renal toxicity, with lower rates
of renal adverse events and serum creatinine increases among
patients treated with meropenem-vaborbactam than best available
therapy – particularly among patients receiving colistin and
aminoglycosides.
Keith S. Kaye, MD, MPH, Professor of Medicine at the University
of Michigan, and the principal investigator for TANGO-2, stated,
“We are grateful for the oversight of the DSMB and for their
recommendations. This real-world study involving critically-ill,
complex patients met its aims at this interim analysis. Results of
TANGO-2 are thoroughly impressive and demonstrate notable efficacy
and safety advantages of meropenem-vaborbactam compared to ‘best
available therapy’ in the treatment of patients with selected
serious infections, suspected or known to be due to CRE. We expect
to present details of the TANGO-2 data in a peer-reviewed
publication and at a medical conference in the future.”
Michael Dudley, PharmD, Senior Vice President, Head of R&D
and Co-Leader for The Medicines Company’s Infectious Disease
Business, added, “We are grateful to the patients and families that
participated in this trial. We have followed the DSMB’s advice and
ended randomization into the trial. We are amending the study
protocol to now enroll patients only into the meropenem-vaborbactam
treatment group. We expect this extension of TANGO-2 will build on
our body of knowledge of CRE patients – which includes information
from a case series of 256 patients managed at many of the TANGO-2
study sites prior to the start of the trial, which was recently
published in the journal, Open Forum Infectious Diseases. The need
for data on the efficacy and safety of new therapies for treating
CRE is well recognized and has been highlighted by both the U.S.
Centers for Disease Control and Prevention (CDC) and the World
Health Organization (WHO), each of which has prioritized CRE
infections at the top of its list of antimicrobial drug resistance
threats worldwide. We are very pleased with the data on Vabomere
from TANGO-2.”
About TANGO-2
TANGO-2 is a multi-center, randomized, open-label Phase III
clinical trial of meropenem-vaborbactam versus “best available
therapy” in patients with serious infections (complicated urinary
tract infections (cUTI), bacteremia, hospital-acquired or
ventilator-associated bacterial pneumonia, and complicated
intraabdominal infections) suspected or documented to be caused by
CRE. Patients with CRE were randomized to receive either
meropenem-vaborbactam monotherapy or the best available therapy for
up to 14 days. Patients randomized to the best available therapy
arm of the trial were given antimicrobial therapy selected for each
patient by the investigator based on laboratory and other patient
data, and thus represents the current standard of care used for the
treatment of CRE infections.
About Vabomere™ (formerly also known as
Carbavance)
Vabomere™ (meropenem-vaborbactam) is a fixed-dose combination of
the carbapenem, meropenem, and the novel beta-lactamase inhibitor,
vaborbactam. Vabomere is an investigational agent not approved for
commercial use in any market. The combination is being developed to
treat serious gram-negative infections, such as cUTI, including
those infections caused by bacteria resistant to currently
available carbapenems. Vabomere’s development has been supported by
a cost-share contract with the Biomedical Advanced Research and
Development Authority (BARDA).
Vabomere was designed to address gram-negative bacteria that
produce new beta-lactamase enzymes that have spread in the United
States and Europe, particularly the Klebsiella pneumoniae
carbapenemase (KPC) enzyme. KPC-producing bacteria are the
predominant form of CRE in the United States and are classified by
the CDC to be an urgent antimicrobial resistance threat. A Phase
III clinical trial of Vabomere in cUTI and acute pyelonephritis
(TANGO-1) was successfully completed in 2016.
Vabomere has been designated by the U.S. Food and Drug
Administration (FDA) as a Qualified Infectious Disease Product
(QIDP), as authorized under the GAIN Act. It was also granted Fast
Track status by the FDA for the treatment of cUTI and
pyelonephritis. QIDP designation also provides for additional
market exclusivity, if approved.
The NDA for Vabomere was accepted for filing by the FDA with a
priority review classification in February 2017 and a PDUFA date in
the third quarter of 2017. In July 2017, the European Medicines
Agency (EMA) accepted for review a marketing authorization
application (MAA) for Vabomere.
About Carbapenem-Resistant Enterobacteriaceae (CRE)
Enterobacteriaceae comprise a family of gram-negative bacteria
that includes Klebsiella sp., E. coli, Enterobacter sp. and others.
This group of bacteria collectively are largely responsible for
hospital-acquired infections due to gram-negative bacteria.
Enterobacteriaceae has shown increasing resistance to widely-used
beta-lactam class antibiotics due to the production of enzymes
known as beta-lactamases, which degrade these antibiotics. The
worldwide dissemination of newer beta-lactamases, known as
carbapenemases, has been responsible for resistance to carbapenem
and other classes of antibiotics. In the United States, the
Klebsiella pneumoniae carbapenemase enzyme is responsible for over
90% of carbapenemase-mediated resistance in CRE. Patients at
particular risk for CRE infections include the elderly, immune
compromised and those with underlying comorbidities, including
malignancies. Infections due to CRE are associated with high
antibiotic failure rates, high mortality (20% to 50%), and high
cost of care for hospitals, third party payers and society ($10,000
to $84,000 per episode). Due to the paucity of antibiotics with
activity against CRE pathogens, physicians often treat CRE
infections with combinations of older antibiotics, many of which
have significant toxicities, most notably renal toxicity.
In light of the high morbidity and mortality associated with CRE
infections and the critical role of carbapenem antibiotics in the
treatment of resistant gram negative infections, the spread of CRE
has been designated as an urgent antimicrobial resistance threat by
the CDC and a critical priority for new drugs by the WHO.
About The Infectious Disease Business
The Medicines Company Infectious Disease Business (MDCO IDC) is
committed to bringing life-saving antimicrobial products to
patients with the most serious drug-resistant infections –
infections caused by “super bugs” which are no longer treatable
with available antibiotics. MDCO IDC encompasses basic research and
drug discovery focused on bacterial mechanisms of drug resistance;
drug development focused on the most threatening bacterial
diseases; and a distribution and commercial infrastructure that
serves the leading hospitals and healthcare facilities in the
United States. MDCO IDC is currently developing Vabomere to treat
serious gram-negative infections, such as complicated urinary tract
infections, including those infections caused by bacteria resistant
to currently available carbapenems. MDCO IDC has a leading pipeline
of novel agents directed towards existing and emerging
multidrug-resistant bacteria.
Since 2014, we have successfully developed and launched two
antibiotics against serious infections: Orbactiv® (oritavancin) for
the treatment of acute bacterial skin and skin-structure infections
in adults, including those due to methicillin-resistant
Staphylococcus aureus, and a new formulation of Minocin®
(minocycline) for Injection, which is among the few FDA-approved
agents for the treatment of infections due to Acinetobacter
spp., a pathogen classified by the CDC to be a serious
antimicrobial resistance threat. For more information on these
products, including their respective prescribing information,
please see www.orbactiv.com and www.minociniv.com.
About BARDA
In February 2014, The Medicines Company Infectious Disease
Business was awarded a cost-sharing contract by the Biomedical
Advanced Research and Development Authority (BARDA), a division of
the Office of the Assistant Secretary for Preparedness and Response
within the U.S. Department of Health and Human Services (HHS), of
which $55.8 million in federal funds have been obligated to date to
support the development of Vabomere.
In September 2016, The Medicines Company entered into a new
strategic partnership with BARDA that will provide the Company with
up to $132 million to support the development of new antibiotics to
fight drug-resistant, gram-negative infections. The partnership was
established under HHS’s Other Transactional Authority (OTA), and is
a distinctive, flexible, portfolio-based approach to funding drug
development. The Medicines Company was awarded $32 million in
initial funding, and up to an additional $100 million (pending the
availability of funding) over approximately five years, if all
options to extend the partnership are exercised by BARDA. The
initial $32 million award supports a Phase IIIb trial of Vabomere
for the treatment of gram-negative infections in hospital-acquired
bacterial pneumonia and ventilator-associated bacterial pneumonia
(HABP/VABP). The initial award, as well as funding provided under
any subsequent options exercised by BARDA, will also support the
advancement of additional antibiotics in MDCO IDC’s portfolio of
new antibiotic drug candidates targeting drug resistant
bacteria.
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
Vabomere will advance 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 Vabomere
on a timely basis, or at all; whether the Company’s 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 May 5,
2017, 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/20170725005394/en/
The Medicines CompanyMediaMeg Langan, 973-290-6319Vice
Presidentmargaret.langan@themedco.comorInvestorsKrishna Gorti, M.D.,
973-290-6122Vice President, Investor
RelationsKrishna.Gorti@themedco.com
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