Ceftaroline Acetate

Ceftaroline is a next–generation‚ broad–spectrum‚ injectable cephalosporin‚ which combines the advantages of an enhanced gram–positive spectrum‚ including bactericidal anti–MRSA activity‚ with broad gram–negative activity‚ while maintaining the favorable safety profile of cephalosporins. Ceftaroline was developed as a water–soluble pro–drug form of the bactericidal compound (PPI–0903M) by Takeda Chemical Industries‚ Ltd.‚ for parenteral administration. Ceftaroline is being developed as a therapeutic agent for the treatment of bacterial infections caused by gram–positive and gram–negative pathogens‚ including resistant staphylococci and streptococci.

Results of in vitro studies indicate that PPI–0903M (active metabolite) displays excellent activity against gram–positive and gram–negative pathogens‚ including MRSA‚ vancomycin–intermediate Staphylococcus aureus (VISA)‚ vancomycin–resistant Staphylococcus aureus (VRSA)‚ linezolid–resistant Staphylococcus aureus‚ and PRSP. Most notably‚ PPI–0903M offers in vitro activity against MRSA‚ VISA‚ VRSA and PRSP that is equivalent to‚ or better than that of‚ vancomycin and linezolid‚ but unlike these bacteriostatic agents‚ PPI–0903M is bactericidal‚ and also exhibits broad spectrum activity against common gram–negative species. As a member of the beta–lactam class of antibiotics‚ ceftaroline targets penicillin–binding proteins (PBPs) to inhibit the synthesis of the bacterial cell wall. However‚ unlike other beta–lactam antibiotics‚ ceftaroline has a high affinity for PBP2A‚ which occurs in MRSA. No resistant development in MRSA was observed for PPI–0903M during multiple passage study.

In vivo activity of ceftaroline was demonstrated in septicemia infection models against both gram–positive and gram–negative organisms in normal and neutropenic mice. Excellent activity was also demonstrated in thigh muscle infection and pneumonia models and against MRSA.

In May of 2004 a Phase I study was initiated to assess the safety and tolerability of single and repeat doses of ceftaroline in healthy volunteers. This study was successfully completed in September 2004. Based on these results‚ an Investigational New Drug (IND) application was filed with the FDA in December 2004.

A Phase 2 trial of ceftaroline for the treatment of complicated skin and skin–structure infections (cSSSI) was initiated in October 2005 and patient enrollment was completed in April 2006. The Phase 2 studied the efficacy and safety of ceftaroline versus standard therapy in 100 patients recruited from over 20 investigational centers worldwide.  Ceftaroline achieved excellent clinical and microbiological response rates in this study and was very safe and well tolerated. 

Cerexa initiated two Phase 3 trials of Ceftaroline in cSSSI in February 2007.