title: Ceftobiprole Medocaril: BAL5788, JNJ 30982081, JNJ30982081, RO 65-5788, RO 655788.
abstract: Ceftobiprole medocaril [BAL 5788, RO 65-5788, JNJ 30982081] is a prodrug in phase III clinical development with Basilea Pharmaceutica and Cilag AG (Johnson & Johnson) for the potential treatment of serious bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA). Ceftobiprole medocaril is the water-soluble prodrug of the pyrrolidinone cephalosporin, ceftobiprole [BAL 9141, RO 63-9141]. Because of the low water solubility of ceftobiprole, its clinical application was limited and Basilea began its investigations into ceftobiprole medocaril for further development. Ceftobiprole medocaril is being developed for IV administration and is currently undergoing phase III trials for complicated skin and skin structure infections (including MRSA) and hospital-acquired (nosocomial) pneumonia. Ceftobiprole medocaril has a broad spectrum of activity against Gram-positive bacteria (including methicillin-resistant staphylococci, penicillin-resistant pneumococci and Enterococcus faecalis) and Gram-negative bacteria. Ceftobiprole medocaril inhibits all transpeptidases, including the penicillin-binding protein (PBP) 2a, by a unique combination of features. PBP 2a is the primary enzyme responsible for beta-lactam drug resistance in MRSA; PBP 2a also acts as a key defense mechanism by interacting with the bacterial cell wall to form a chemical barricade that is impervious to antibiotics. Ceftobiprole medocaril has been designed specifically to bind to this penicillin-resistant target. Ceftobiprole medocaril is bactericidal and has not shown resistance development in vitro or in stringent animal models. Studies conducted by Basilea have demonstrated that ceftobiprole medocaril is readily converted to ceftobiprole, and shows markedly improved water solubility. In February 2005, Basilea Pharmaceutica AG entered into an exclusive worldwide agreement with Cilag AG International (Johnson & Johnson) to develop, manufacture and market ceftobiprole medocaril. Ortho-McNeil Pharmaceutical (Johnson & Johnson) will market ceftobiprole medocaril in the US, and its affiliate companies, known as Janssen-Cilag, will market the product outside the US (entered as World in the Licensee table). Basilea has retained an option to co-promote ceftobiprole medocaril in the US, major European countries, Japan and China. Johnson & Johnson Pharmaceutical Research and Development LLC will develop ceftobiprole medocaril in collaboration with Basilea. Roche previously retained an opt-in right on ceftobiprole medocaril. However, following Roche's decision not to exercise this right in May 2004, Basilea gained full global commercialisation rights for ceftobiprole medocaril. Roche retains its major shareholding in Basilea. Ceftobiprole medocaril is currently in phase III trials for complicated skin and skin structure infections due to MRSA, and nosocomial pneumonia (including ventilator-associated pneumonia) due to suspected or proven MRSA, and community-acquired pneumonia. The US FDA has granted fast-track status to the compound for these two indications. Phase III results are expected in 2006 and an NDA is expected to be submitted to the FDA in 2007. An additional pivotal phase III trial (STRAUSS 2, STudy of Resistant Staphyloccocus aureus in Skin and Skin structure infections) of ceftobiprole medocaril was initiated in October 2005 for complicated skin infections, including diabetic foot infections. This trial will be conducted in conjunction with Johnson & Johnson Pharmaceutical Research and Development.
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D013207:Staphylococcal Skin Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C505439:ceftobiprole medocaril