Ceftobiprole (Molecule of the Month for January 2010)
Ceftobiprole (band names Zeftera or Zevtera) is a 5th generation cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, Pseudomonas aeruginosa, and Enterococci. It was discovered by Basilea Pharmaceutica and was developed by Johnson & Johnson Pharmaceutical Research and Development. It has been shown to be statistically non-inferior to the combination of vancomycin and ceftazidime for the treatment of skin and soft tissue infections.
Ceftobiprole is a new drug for the treatment of the increasing number of patients with severe methicillin-resistant Staphylococcus aureus (MRSA) infections. Ceftobiprole’s broad spectrum activity, which encompasses Gram-positive and Gram-negative bacteria, including anti-pseudomonal activity similar to cefepime, suggests the potential for empirical monotherapy for complicated skin and skin structure infections as well as healthcare-associated pneumonia. Ceftobiprole inhibits the 2a penicillin-binding protein (pbp) of Methicillin-resistant Staphylococcus aureus and the 2x pbp of Streptococcus pneumoniae as well as the classic PBP-2 of MSSA. Ceftobiprole is resistant to staphylococcal β-lactamase.
Basel, Switzerland, April 9, 2010 - Basilea Pharmaceutica Ltd. (SIX: BSLN) announces that Janssen-Ortho Inc., a Johnson & Johnson company, has in consultation with Health Canada decided to discontinue sale of ceftobiprole (ZEFTERA™) for the treatment of complicated skin and skin structure infections (cSSSI) in Canada. Janssen-Ortho Inc., the holder of the Market Authorization in Canada, is discontinuing sale of ZEFTERA™ effective April 16, 2010. This action is being taken by Janssen-Ortho Inc. following discussions with Health Canada in response to recent regulatory recommendations in the United States and European Union to not approve ZEFTERA™ for cSSSI due to concerns regarding the conduct of clinical trials. ZEFTERA™ was authorized in Canada in June 2008 for the treatment of cSSSI. There have been no safety observations that would be in conflict with the approved label of ZEFTERA™ in Canada. The decision to discontinue sale of the product in the Canadian market does not preclude the submission of a new application for market authorization in the future. Recently, the European Committee for Medicinal Products for Human Use (CHMP) indicated that, although the study results suggested that ceftobiprole is beneficial to patients, it was concerned about how reliable the trial results were. The Committee therefore recommended that, in light of the uncertainty surrounding the results, ceftobiprole should not be granted marketing authorization for the treatment of complicated skin and soft tissue infections at this time. The sponsor Janssen-Cilag International NV, a Johnson & Johnson company, submitted a request for re-examination of the negative opinion by the CHMP. In December 2009, the U.S. Food and Drug Administration (FDA) issued to the sponsor of the US filing, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., a Complete Response Letter on ceftobiprole for the treatment of cSSSI, indicating that the Agency cannot approve the New Drug Application in its present form. The Agency determined that data from the phase III clinical trials could not be relied upon because of concerns regarding the overall data integrity for both studies.
Formal Chemical Name (IUPAC)
(6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-ylidene)- 2-nitroso-1-oxoethyl]amino]-8-oxo-3-[(E)-[2-oxo-1-[(3R)- 3-pyrrolidinyl]-3-pyrrolidinylidene]methyl]-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Update by Karl Harrison
(Molecule of the Month for January 2010 )
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