Cubist Pharmaceuticals, Inc. announced presentations of new in vitro and animal data on its investigational antibiotic Cidecin (daptomycin for injection). The data was presented at the 103rd General Meeting of the American Society for Microbiology (ASM), in Washington, DC. The Cidecin New Drug Application (NDA) is currently being reviewed by the U.S. Food & Drug Administration (FDA) under priority review status.
First isolate of Staphylococcus aureus to be fully resistant to the drug vancomycin was reported by the Centers for Disease Control and Prevention (CDC) in July 2002. Data previously presented in September 2002 demonstrated daptomycin to be the most rapidly bactericidal (killing) of all agents studied against this strain in vitro. A second isolate of vancomycin-resistant S. aureus (VRSA) was reported in September 2002. In Poster #A-075, Drs. P. C. Appelbaum of Penn State Hershey Medical Center, Hershey, PA, and F. C. Tenover of the CDC, Atlanta, GA, presented in vitro data comparing the activity of commercially available drugs, including linezolid, quinupristin/dalfopristin and trimethoprim/sufamethoxazole, to the activity of experimental agents, including daptomycin, oritavancin and tigecycline, against this second multi-drug resistant VRSA isolate. In this study, bactericidal activity was defined as the lowest concentration at which the agent reduced the original inoculum by at least 3 log10 colony forming units (cfu)/mL at each time point. Daptomycin was the only agent studied that demonstrated bactericidal activity at the 3-hour time point at one times its minimum inhibitory concentration (MIC).
The results of another in vitro study were presented by Dr. K. H. Rand of the Department of Pathology at the University of Florida, Gainesville, FL in Poster #C-091. Following his previous study demonstrating that daptomycin had marked synergistic in vitro activity when used in combination with rifampin and ampicillin against vancomycin-resistant enterococci (VRE), Dr. Rand designed this study to look for synergy between daptomycin and the semi-synthetic penicillin oxacillin against 18 strains of methicillin-resistant S. aureus (MRSA) in vitro. At concentrations well below daptomycin's MIC against MRSA, bactericidal synergy was observed in 18/18 (100 per cent) MRSA strains at one half daptomycin MIC, and even in 11/18 (61 per cent) at one quarter daptomycin MIC. The poster concluded that "the uniformity of both bactericidal activity and synergy make the combination of daptomycin and oxacillin very promising for the treatment of MRSA, but further studies are needed to elucidate the mechanisms and determine in vivo efficacy."
In Poster #A-025, Cubist scientists reported results on the efficacy of daptomycin in a rodent fibrin clot model of endocarditis caused by MRSA. This study examined the efficacy of daptomycin, vancomycin and linezolid against MRSA in subcutaneous fibrinogen and thrombin clots, similar to the fibrous vegetations seen in human endocarditis. Results demonstrated that daptomycin effectively penetrated the clots containing MRSA and that both vancomycin and linezolid were less effective than daptomycin in killing MRSA in this endocarditis model in rodents. Cubist is currently investigating the safety and efficacy of Cidecin in the treatment of endocarditis caused by S. aureus in an ongoing Phase 3 clinical trial.