The Medicines Company has acquired Rempex Pharmaceuticals, a company with multiple potential new therapies focused on multi-drug resistant gram-negative bacteria.

Clive Meanwell, M.D., Ph.D., chairman and chief executive officer of The Medicines Company, said, "Acute and intensive care hospitals around the world face rapid and increasing antibacterial resistance, especially to gram-negative pathogens. The assets of Rempex, particularly Carbavance, will allow us to intensify our efforts to save lives, alleviate suffering and contribute to the economics of healthcare by serving leading hospitals."

The Medicines Company paid Rempex equity holders $140 million in an upfront payment, and will pay Rempex milestones of up to $334 million. The Medicines Company has acquired several anti-infective assets in the transaction: Carbavance, Minocin IV, RPX-602 and a preclinical developmental program of novel investigational agents.

Carbavance is Rempex's investigational agent that is a combination of a novel beta-lactamase inhibitor (RPX7009) with a carbapenem for intravenous treatment of hospitalized patients with serious infections. RPX7009 is the first of a novel class of beta-lactamase inhibitors designed by Rempex to inhibit the KPC (Klebsiella pneumoniae carbapenemases) enzyme, the primary resistance mechanism to carbapenems. KPC-producing bacteria are the predominant form of carbapenem-resistant Enterobacteriaceae (CRE) globally and are classified by the U.S. Centers for Disease Control and Prevention (CDC) to be an urgent antimicrobial resistance threat. Carbavance has completed phase I dose-escalation studies in normal subjects and is expected to enter registration studies in 2014.

Michael Dudley, PharmD, senior vice president of R&D and chief scientific officer of Rempex, said, "Carbapenems are among the most potent and safe antibiotics, and are now regarded as one of the last lines of defense following worldwide dissemination of cephalosporin resistance. We anticipate that Carbavance will profile better than any antibiotic on the market or currently in clinical development for multi-drug resistant gram-negative infections."

The Medicines Company will market Minocin IV (Minocycline for Injection) in the U.S. for resistant infections due to Acinetobacter, which frequently is isolated in hospitals and is especially prevalent in intensive care units. The CDC recently classified multidrug-resistant Acinetobacter as a serious threat in the U.S. According to the CDC, about 63% of Acinetobacter is considered multidrug-resistant.

Minocin IV is approved for the treatment of these multi-drug resistant infections, and surveillance data show a vast majority of isolates of Acinetobacter baumannii are susceptible to minocycline in vitro. Minocycline is among the most active agents studied by Rempex in vitro against this pathogen, including multi-drug resistant strains. The Medicines Company expects to submit for U.S. approval a novel, improved formulation of Minocin IV (RPX-602) in 2014.

The Medicines Company also will continue Rempex's ongoing discovery program to identify other novel beta-lactamase inhibitor-based combination products designed to provide considerable versatility in overcoming resistance mechanisms such as extended-spectrum beta-lactamase (ESBL), serine carbapenemase and metallo beta-lactamase (MBL) production in gram-negative organisms.

"The most serious gram-negative infections are in seriously ill hospitalized patients, and the most common pathogens are Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter. Rempex has leading programs for all three," said Matthew Wikler, M.D., vice president, infectious disease care, at The Medicines Company.