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Sivextro

Generic name: tedizolid phosphate
Treatment for: Skin and Structure Infection

Update: Sivextro (tedizolid phosphate) Now FDA Approved - June 20, 2014

Cubist Announces Publication of Pivotal Data from Sivextro (tedizolid phosphate) ESTABLISH-2 Trial

LEXINGTON, Mass.--(BUSINESS WIRE) June 6, 2014 -- 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.

Source: Cubist Pharmaceuticals, Inc.

Posted: June 2014

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