Discovery and development of Surotomycin

Surotomycin   is a novel, orally administered, cyclic lipopeptide antibiotic in development for the treatment of Clostridium difficile associated diarrhea (CDAD).  Surotomycin was derived via semi-synthesis from the natural product daptomycin.  Surotomycin has potent activity against Gram positive organisms, including C. difficile and VRE and is bactericidal against exponential and stationary phase bacteria. By spontaneous and serial passage methods, surotomycin displays a low potential for resistance development.  No cross-resistance is seen with other agents used in the treatment of C. difficile.  In the hamster model of CDAD, surotomycin and vancomycin both demonstrated potent efficacy in resolving initial disease onset, even at very low doses, and a similar dose- and time-dependent pattern with respect to rates of CDAD recurrence.

Surotomycin has limited activity against Gram-negative bacilli including bacteroides.  As a result, while both surotomycin and vancomycin alter the gastrointestinal flora of treated animals and patients, the patterns of alteration are different and may influence clinical outcomes.  Surotomycin is also more rapidly bactericidal in vitro than vancomycin, and lipopeptides are known to retain activity against stationary phase bacteria; these features could also influence clinical outcomes.  In Phase 2 trials, surotomycin dosed at 125 or 250 mg/day produced equivalent end of therapy cure rates to vancomycin (92.4%, 86.6%, and 89.4%, respectively).  However, surotomycin was superior with regards to recurrence rates (27.9%, 17.2%, 35.6%), resulting in higher rates of sustained cure (66.7%, 70.1%, 56.1%).  Ongoing Phase 3 studies will determine whether these findings are reproducible in a broader patient population.