Results from first prospectively designed
Phase 3 clinical trial consistent with final FDA guidance for acute
bacterial skin and skin structure infections (ABSSSI)
Cubist Pharmaceuticals, Inc. (NASDAQ: CBST) today announced that
The Lancet Infectious Diseases published online the positive
results from ESTABLISH-2, a pivotal Phase 3 clinical trial of the
investigational antibiotic SIVEXTRO™ (tedizolid phosphate), which
is being developed for the treatment of acute bacterial skin and
skin structure infections (ABSSSI) and complicated skin and soft
tissue infections (cSSTI). The results will also appear in a
forthcoming print issue of the journal. The authors note that
ESTABLISH-2 was the first prospectively designed clinical trial
consistent with the fundamental elements outlined in the final U.S.
Food and Drug Administration (FDA) ABSSSI Guidance released in
2013.
SIVEXTRO is a once daily oxazolidinone being developed for both
intravenous (I.V.) and oral administration for the treatment of
serious infections caused by certain Gram-positive bacteria,
including those caused by methicillin-resistant Staphylococcus
aureus (MRSA). The published data are based on one of the two
global Phase 3 clinical studies of SIVEXTRO (ESTABLISH-1 and
ESTABLISH-2), which met the primary and secondary endpoints defined
by the FDA and European Medicines Agency (EMA). The clinical trials
enrolled 1,333 people in the U.S., Europe and other regions
worldwide.
As outlined in The Lancet Infectious Diseases, a focus of the
ESTABLISH-2 clinical trial was to evaluate the efficacy and safety
of the I.V. to oral transition of SIVEXTRO in the treatment of
ABSSSI. The randomized, controlled Phase 3 clinical trial compared
SIVEXTRO 200 mg given as a once daily dose for six days with
linezolid 1200 mg divided as a twice daily dose for 10 days, both
administered by I.V. with a possible switch to oral study
treatment, when pre-specified criteria were met. Results showed a
six-day course of once-daily SIVEXTRO to be non-inferior to 10 days
of twice-daily linezolid for the treatment of ABSSSI. In the
ESTABLISH-2 study, the adverse event rates were similar for both
SIVEXTRO and linezolid treated patients. Gastrointestinal adverse
events (diarrhea, nausea and vomiting) were the most commonly
reported in both treatment groups.
“Publication of ESTABLISH-2 clinical trial results in The Lancet
Infectious Diseases contributes important information to the
infectious disease community worldwide about SIVEXTRO,” said Steven
Gilman, Ph.D., Executive Vice President of Research and Development
and Chief Scientific Officer of Cubist Pharmaceuticals. “These data
provide further support for the potential of SIVEXTRO as a novel
treatment option that might be used in the transition from I.V. to
oral therapy in a short, six-day course of treatment for patients
with serious skin infections.”
“Acute bacterial skin and skin structure infections are a common
problem that we see every day in emergency departments and clinics
across the U.S. These infections can be devastating to patients,
and are among the most common infections treated in hospitals. MRSA
is recognized as a frequent cause of these infections, and is
now declared a serious public health threat in the U.S. because of
increasing incidence in the last decade,” said Gregory J. Moran,
M.D., Clinical Professor, UCLA Dept. of Emergency Medicine. “With
limitations of some existing therapies, including resistance to
certain agents, there is a need for new antibiotics in addition to
a focus on appropriate use. It is encouraging to see these clinical
trial data in hospital and outpatient settings, as SIVEXTRO may
become a potential treatment option for acute bacterial skin and
skin structure infections, including those caused by MRSA.”
Data from the ESTABLISH-2 study, along with data from the
previously published ESTABLISH-1 study, served as the basis for
Cubist’s New Drug Application (NDA) for SIVEXTRO, for which Cubist
is seeking approval in acute bacterial skin and skin structure
infections (ABSSSI). The FDA accepted the NDA in December 2013 for
Priority Review, assigning a Prescription Drug User Fee Act (PDUFA)
action date of June 20, 2014. On March 31, 2014 the FDA
Anti-Infective Drug Advisory Committee (AIDAC) voted unanimously to
recommend approval of SIVEXTRO. The Company also recently announced
that the EMA accepted for review its Marketing Authorization
Application (MAA) for SIVEXTRO, for which Cubist is seeking
approval for the treatment of complicated skin and soft tissue
infections (cSSTI).
About Serious Skin, Skin Structure and Soft Tissue
Infections
Acute bacterial skin and skin structure infections (ABSSSI) are
also referred to as complicated skin and soft tissue infections
(cSSTI) (in Europe). These infections, which are a significant and
growing problem throughout the world, involve deeper tissue or
require surgical intervention (e.g., cellulitis, major cutaneous
abscesses and infected wounds) or are associated with a significant
underlying disease (e.g., diabetes or systemic immunosuppression)
that complicates response to therapy. A variety of pathogens may be
identified in ABSSSI/cSSTI but the two most common Gram-positive
pathogens are Staphylococcus aureus and Streptococcus pyogenes. The
significant increase in the incidence of methicillin-resistant
Staphylococcus aureus (MRSA) healthcare-associated infections
(HAIs), as well as community infections, has resulted in a need for
therapies to address serious skin, skin structure and soft tissue
infections that are effective against MRSA.
About MRSA
The European Centre for Disease Prevention and Control (ECDC)
estimates that more than four million European Union (EU) patients
acquire healthcare-associated infections (HAIs) annually, resulting
in 37,000 deaths, and that a large proportion of these deaths are
due to the most common multidrug-resistant bacteria, including
methicillin-resistant Staphylococcus aureus (MRSA). According to
the ECDC, MRSA is still the most commonly identified
antimicrobial-resistant pathogen in hospitals in many parts of the
world, including Europe, the Americas, North Africa, the
Middle-East, and Asia. Data from the Eurosurveillance journal
estimates MRSA infections affect more than 150,000 patients
annually in the EU. According to the U.S. Centers for Disease
Control and Prevention (CDC) “Antibiotic resistance threats in the
United States, 2013” report, each year more than two million
Americans develop infections from antibiotic-resistant bacteria.
One of the serious public health threats identified by the CDC is
MRSA, which continues to be a clinical and economic burden. Based
on CDC data, there are 80,461 severe MRSA infections and 11,285
deaths from MRSA in the U.S. per year.
About SIVEXTRO™ (tedizolid phosphate)
Tedizolid phosphate (formerly TR-701), now known as SIVEXTRO, is
a novel oxazolidinone antibiotic drug candidate that is rapidly
converted in vivo by phosphatases to the microbiologically active
moiety TR-700. TR-700 acts by binding to the bacterial 50S
ribosomal subunit thereby inhibiting protein synthesis. Tedizolid
is being developed for both I.V. and oral administration in the
potential treatment of acute bacterial skin and skin structure
infections (ABSSSI), also referred to as complicated skin and soft
tissue infections (cSSTI). Tedizolid is also being developed for
potential use in nosocomial pneumonia (hospital-acquired bacterial
pneumonia [HABP] and ventilator-associated bacterial pneumonia
[VABP]). Two Phase 3 studies, conducted in the U.S., Europe and
other regions worldwide, in cSSTI and ABSSSI demonstrated that
tedizolid 200 mg once daily for six days was statistically
non-inferior to 10 days of linezolid 600 mg twice daily for the
primary efficacy endpoints. Secondary endpoints were also met. In
these studies, the adverse event rates were similar for both
tedizolid and linezolid treated patients. Gastrointestinal adverse
events (diarrhea, nausea and vomiting) were the most commonly
reported in both treatment groups. For more information visit
http://www.cubist.com/products/tedizolid, or view a supplement to
Clinical Infectious Diseases.
About Cubist’s Commitment to Antibiotic R&D
Cubist has a growing commitment to global public health through
its leadership in the discovery, development and commercialization
of novel antibiotics to treat serious and life-threatening
infections caused by a broad range of increasingly drug-resistant
bacteria. The Company hopes to deliver at least four new
antibiotics in support of the Infectious Diseases Society of
America (IDSA) goal of 10 new antibiotics by 2020. Cubist expects
to invest approximately $400M USD in 2014 on antibacterial R&D
and approximately 75% of its employee base is focused on the
research, development, commercialization and support of
antibiotics.
About Cubist
Cubist Pharmaceuticals, Inc. is a global biopharmaceutical
company focused on the research, development, and commercialization
of pharmaceutical products that address significant unmet medical
needs in the acute care environment. Cubist is headquartered in
Lexington, Massachusetts, with a central international office
located in Zurich, Switzerland. Additional information can be found
at Cubist’s web site at www.cubist.com. Also, connect with Cubist
on Twitter @cubistbiopharma and @cubistcareers, LinkedIn, or
YouTube.
Forward Looking Statements
This press release contains forward-looking statements. Any
statements contained herein which do not describe historical facts,
including but not limited to, statements regarding: positive
results from our Phase 3 clinical studies of SIVEXTRO and the
expected timing for publishing the results in print format; the
therapeutic potential of SIVEXTRO; the expected timing of the FDA’s
action date for our SIVEXTRO New Drug Application submission; our
aspirations to achieve a portion of the IDSA goal of 10 new
antibiotics by 2020; and the level of our financial and personnel
commitments towards antibiotic research, development and
commercialization, are forward-looking statements which involve
risks and uncertainties that could cause actual results to differ
materially from those discussed in such forward-looking statements.
Such risks and uncertainties include, among others: regulatory
developments in Europe and the U.S., including the risk that the
EMA, EC, FDA and other foreign regulatory authorities may not agree
with our interpretation of the results from the clinical studies of
SIVEXTRO, may not approve on a timely basis or at all, our
marketing authorization applications for SIVEXTRO or may require
additional data, analysis, information or further studies that may
not be clinically feasible or financially practicable; that the
FDA’s review and decision on our SIVEXTRO NDA submission may be
affected by issues not discussed by the AIDAC and the FDA is not
bound by and may not agree with the AIDAC’s recommendation; any
marketing approval for SIVEXTRO may impose significant limitations
on its use and additional post-marketing requirements; our ability
to obtain adequate pricing and reimbursement levels for SIVEXTRO;
our ability to successfully commercialize SIVEXTRO, including as a
result of regulatory authorities’ decisions regarding labeling and
other matters, including adverse side effects, that could affect
its availability or commercial potential; competitive risks from
current and future therapeutic alternatives to tedizolid; our
ability to maintain and enforce intellectual property protection
for SIVEXTRO; we may not be able to submit additional marketing
authorization applications for SIVEXTRO on our anticipated
timelines; additional clinical trials of SIVEXTRO, including in
HABP/VABP, may produce negative or inconclusive results or may not
be initiated or conducted in a timely manner; technical
difficulties or excessive costs relating to the manufacture or
supply of tedizolid, including our ability to work with our third
party contract manufacturers that manufacture and supply SIVEXTRO
on our behalf; our ability to work with, and the performance of our
third party contract research organizations that help us conduct
our clinical trials; we may encounter other unanticipated or
unexpected risks with respect to the development or manufacture of
SIVEXTRO; the fact that drug discovery and development is complex,
time consuming, expensive and fraught with a high risk of failure;
and those additional factors discussed in our most recent annual
report on Form 10-K and quarterly report on Form 10-Q filed with
the Securities and Exchange Commission. We caution investors not to
place considerable reliance on the forward-looking statements
contained in this press release. These forward-looking statements
speak only as of the date of this document, and we undertake no
obligation to update or revise any of these statements.
INVESTORS:Cubist Pharmaceuticals,
Inc.Eileen C. McIntyre, 781-860-8533Vice President, Investor
Relationseileen.mcintyre@cubist.comorMEDIA:Cubist Pharmaceuticals, Inc.Elizabeth
Dunavant, 781-860-8680Director, Product
Communicationselizabeth.dunavant@cubist.com