Surotomycin Fails To Show Benefit Over Vancomycin in C. Difficile Treatment in Phase 3 Trial

A phase 3 trial assessed the efficacy and safety of surotomycin (CB-183,315), a novel bactericidal cyclic lipopeptide, versus oral vancomycin in treatment of Clostridium difficile infection (C. diff).

In the randomized, double-blind, active controlled, international multicenter trial, 285 subjects with C. diff, confirmed by a positive toxin result, were randomized to receive, 250 mg oral surotomycin twice daily, alternating with placebo twice daily, while 292 patients received vancomycin, 125 mg 4 times daily, orally for 10 days.

“Surotomycin has a narrow spectrum of activity, demonstrating low resistance rates and rapid activity against C. difficile with similar dose- and time-dependent pharmacodynamics to vancomycin in resolving CDI in a hamster model,” Sahil Khanna MBBS, division of gastroenterology and hepatology, Mayo Clinic, said.

Surotomycin however, did not demonstrate superiority for key secondary endpoints including sustained clinical response and clinical response over time, failing to show benefit over vancomycin.

Clinical response over time and sustained clinical response were monitored until the end of the trial through a follow-up period of 30—40 days with a maximum of 100.

At the end of the treatment, the clinical response for those taking surotomycin (83.4%) was non-inferior to vancomycin (82.1%) with a difference of 1.4%.

Through follow-up days, clinical response was no superior to surotomycin, nor sustained a clinical response, 63.3% versus 59% difference. Both treatments were generally well tolerated.

Surotomycin demonstrated non-inferiority to vancomycin for C. difficile clinical response at the end of trial. It did not demonstrate superiority to vancomycin for clinical response over time or sustained clinical response rate.

To be included in the study, participants must sign a consent form, be 18 years or older and 90 or younger, have diarrhea at least 3 times throughout 1 day, or 200 mL or liquid stool if using a rectal device, test positive for C. diff, and if female, must not be pregnant or nursing.

Based on the trial results, the development program of surotomycin has been discontinued.

This follows previously reported results of a parallel phase 3 trial in which surotomycin failed to meet non-inferiority criteria relative to vancomycin for primary and key secondary endpoints.

The primary outcomes in the parallel study included the proportion of subjects with a clinical outcome of cure 2 days after the last dose of study drug, while the secondary outcome measures were to demonstrate a clinical response over time based on the length of time it takes for subjects to fail treatment, recur, die or become lost to follow-up day until day 40 — 30 days after the last dose of study drug — and the proportion of subjects who sustain a clinical outcome of cure until day 50, 30 days after last dose of study drug.

In this second phase 3 trial, surotomycin demonstrated non-inferiority to vancomycin for C. difficile clinical response at end of treatment, similarly to vancomycin for sustained clinical cure.

The study, “Surotomycin versus vancomycin in adults with Clostridium difficile infection: primary clinical outcomes from the second pivotal, randomized, double-blind, Phase 3 trial” can be found in the Journal of Antimicrobial Chemotherapy.