Surotomycin meets non-inferiority endpoint, fails to show benefit over vancomycin in C. difficile
A similar proportion of patients with Clostridium difficile infection showed clinical response at the end of treatment with surotomycin vs. vancomycin in a pivotal phase 3 trial.
However, surotomycin did not demonstrate superiority for key secondary endpoints including sustained clinical response and clinical response over time, and therefore failed to show benefit over vancomycin.
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.
“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, of the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., told Healio Gastroenterology and Liver Disease. In this second phase 3 trial, “surotomycin demonstrated non-inferiority to vancomycin for CDI clinical response at end of treatment. It was similar to vancomycin for sustained clinical cure.”
In this double-blind, international multicenter trial, Khanna and colleagues randomly assigned 285 patients with confirmed CDI to receive 250 mg oral surotomycin twice daily alternating with placebo twice daily, and 292 to receive 125 mg oral vancomycin four times daily for 10 days.
At the end of treatment, clinical response with surotomycin (83.4%) was non-inferior to vancomycin (82.1%), with a difference of 1.4% (95% CI, 4.9-7.6).
Through 30 to 40 days of follow-up, clinical response over time was not superior to surotomycin, nor was sustained clinical response (63.3% vs. 59%; difference, 4.3%; 95% CI, 3.6-12.2).
Both treatments were generally well tolerated, with typical treatment-emergent adverse events occurring in 52.4% of patients treated with surotomycin and 60.1% of those treated with vancomycin.
“Interestingly, in the hypervirulent strain of CDI, recurrence rate was lower for surotomycin vs. vancomycin,” Khanna said, though he and colleagues noted in the study manuscript that “this finding is nominal due to a lack of multiplicity control.”
Based on the results of these trials, the surotomycin development program has been discontinued, but “the non-inferiority of surotomycin to vancomycin observed in the current trial is in contrast with the parallel trial,” investigators wrote. – by Adam Leitenberger
Disclosures: This study was funded by Merck. Khanna reports he has served as an advisor to Summit Pharmaceuticals and serves as a consultant to Rebiotix and Assembly Biosciences. Please see the full study for a list of all other researchers’ relevant financial disclosures.