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.