The Medicines Company Announces First Patient Enrollment in Phase 3 Studies of CARBAVANCE™ in Development for the Treatment of Serious Bacterial Infections Due to Gram-Negative Bacteria

05 Nov 2014

The Medicines Company (NASDAQ:MDCO) today announced enrollment of the first patient in its Phase 3 clinical trial program for CARBAVANCE™ (meropenem/RPX7009), an investigational intravenous antibiotic under development for the treatment of serious bacterial infections due to gram-negative bacteria, particularly KPC (Klebsiella pneumoniae carbapenemase)-producing carbapenem-resistant Enterobacteriaceae (CRE).

CARBAVANCE is a combination of the carbapenem antibiotic, meropenem, combined with RPX7009, the first of a novel class of beta-lactamase inhibitors. Beta-lactamase inhibitors are agents that inhibit bacterial enzymes, which destroy beta-lactam antibiotics and result in resistance to first line as well as "last defense" antimicrobials used in hospitals. Gram-negative bacterial infections are widely considered to be one of the largest areas of unmet medical need, as these pathogens are growing increasingly resistant to existing therapies with few antibiotics in development.

“We are excited to be initiating our two clinical trials with CARBAVANCE,” said Jeff Loutit, Vice President and Chief Medical Officer for Infectious Disease Care at The Medicines Company. “RPX7009 was developed specifically to have activity against KPC producing strains of CRE, and meropenem is a carbapenem with a proven track record of efficacy and safety. We believe CARBAVANCE, upon approval, has the potential to provide health care professionals and patients with a new option for the treatment of serious gram-negative infections.”

The first CARBAVANCE clinical trial is designed to evaluate the efficacy, safety and tolerability of CARBAVANCE in approximately 850 patients with complicated urinary tract infections (cUTI) or acute pyelonephritis (AP). The second trial is designed to evaluate the safety, efficacy and tolerability of CARBAVANCE in approximately 150 patients with suspected or known serious infections due to CRE across multiple indications.

Results from both CARBAVANCE Phase 3 trials are expected in 2016.

Antibiotic resistance in gram-negative bacteria has increased markedly in the last decade, leaving clinicians and critically-ill patients few choices for treatment. The CDC has designated CRE as an urgent antimicrobial resistance threat. This has created an urgent need for new agents that has been recognized worldwide by health authorities. “With acute and intensive care hospitals around the world facing rapid and increasing antibacterial resistance, the development of CARBAVANCE is the type of innovation we need as physicians to address such a threat,” stated Keith S. Kaye, M.D., M.P.H., Professor of Internal Medicine and Infectious diseases at Wayne State University School of Medicine, Corporate Director of Infection Prevention, Hospital Epidemiology and Antimicrobial Stewardship at the Detroit Medical Center.

In January 2014, the U.S. Food and Drug Administration (FDA) designated CARBAVANCE as a Qualified Infectious Disease Product (QIDP). The QIDP designation provides CARBAVANCE priority review by the FDA, eligibility for the FDA's "fast track" status, and an additional five years of exclusivity upon approval of the product for intravenous use in six indications. These include complicated urinary tract and intra-abdominal infections, hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia, and febrile neutropenia. The QIDP designation was granted pursuant to the Generating Antibiotic Incentives Now (GAIN) Act, included in the FDA Safety and Innovation Act (FDASIA) that was signed into law in 2012.

In February 2014, the CARBAVANCE program, through our subsidiary Rempex Pharmaceuticals, was awarded a contract by the Biomedical Advanced Research and Development Authority (BARDA) that included an initial commitment of $19.8 million and subsequent option periods over 5 years that, if completed, would bring the total value of the award to approximately $90 million to support the development of CARBAVANCE. On October 30, 2014, BARDA awarded Rempex the second option, bringing the total commitment to date by BARDA to $37.8 million. The BARDA contract (HHSO100201400002C) is a cost-sharing arrangement that includes non-clinical development activities, clinical studies, manufacturing, and associated regulatory activities designed to gain US approval of CARBAVANCE for treatment of serious gram-negative infections. Studies are also planned to assess the potential usefulness of CARBAVANCE for treatment of certain gram-negative bioterrorism agents.

About the CARBAVANCE trials

TANGO 1: A Phase 3, Multi-Center, Randomized, Double-Blind, Double-Dummy Study to Evaluate the Efficacy, Safety, and Tolerability of CARBAVANCE (meropenem/RPX7009) Compared to piperacillin/tazobactam in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, in Adults. Approximately 850 study subjects will be randomly assigned (1:1) to receive either CARBAVANCE IV or piperacillin/tazobactam each given intravenously for up to 10 days. Subjects in both arms who meet protocol defined criteria of improvement can be switched to oral levofloxacin after a minimum of 5 days of IV therapy.

TANGO 2: A Phase 3, Multi-Center, Randomized, Open-Label Study of CARBAVANCE (meropenem/RPX7009) Versus “Best Available Therapy” in Subjects with Selected Serious Infections Due to Carbapenem-Resistant Enterobacteriaceae. Approximately 150 study subjects with cUTI, nosocomial pneumonia and/or bacteremia will be randomly assigned (2:1) to CARBAVANCE IV or “Best Available Therapy” for up to 14 days.

About CARBAVANCE

CARBAVANCE, an investigational agent not approved for commercial use in any market, is a combination of meropenem and RPX7009 administered as a fixed combination by IV infusion and is being developed to treat serious gram-negative infections, such as cUTIs, including those infections caused by bacteria resistant to currently available carbapenems.

CARBAVANCE was designed to address gram-negative bacteria that produce new beta-lactamase enzymes that have spread in the US and Europe, including strains producing the Klebsiella pneumoniae carbapenemase (KPC) enzyme. KPC-producing bacteria are the predominant form of carbapenem-resistant Enterobacteriaceae (CRE) in the US and are classified by the US Centers for Disease Control and Prevention (CDC) to be an urgent antimicrobial resistance threat.

About The Medicines Company

The Medicines Company's purpose is to save lives, alleviate suffering and contribute to the economics of healthcare by focusing on 3000 leading acute/intensive care hospitals worldwide. Its vision is to be a leading provider of solutions in three areas: serious infectious disease care, acute cardiovascular care and surgery and perioperative care. The company operates in the Americas, Europe and the Middle East, and Asia Pacific regions with global centers today in Parsippany, NJ, USA and Zurich, Switzerland.

Forward-Looking Statements

Statements contained in this press 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" and "expects" 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 the Company's products will advance in the clinical trials process on a timely basis or at all, whether the Company will make regulatory submissions for product candidates on a timely basis, whether its regulatory submissions will receive approvals from regulatory agencies on a timely basis or at all, whether physicians, patients and other key decision makers will accept clinical trial results 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 SEC on August 4, 2014, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.


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