A final line has been drawn under cadazolid as an initially promising but ultimately disappointing treatment for the management of C. difficile infections.
The IMPACT 1 and 2 trials of the novel quinoxolidinone antibiotic versus vancomycin, published together in The Lancet Infectious Diseases, failed to show overall superiority of cadazolid over vancomycin.
“Further commercial development of cadazolid for C difficile infection is unlikely,” the investigators predicted.
In the IMPACT 1 trial, which included sites in Australia, non-inferiority to vancomycin was demonstrated.
In the study, 84% of patients treated with 250 mg cadazolid twice daily had a clinical cure compared to 85% of patients treated with 125 mg vancomycin four times daily on an intention-to-treat basis.
However non-inferiority was not shown in the IMPACT 2 trial with clinical cure in 81% of patients on cadazolid compared to 86% of patients treated with vancomycin.
Per-protocol, cadazolid achieved clinical cure in 88% of patients versus 92% with vancomycin in the IMPACT 1 trial and 87% with cadazolid versus 92% with vancomycin in IMPACT 2.
“Superiority of cadazolid over vancomycin for sustained cure was not shown,” the researchers said.
“In both studies, cadazolid had a similar safety profile to vancomycin.”
“Both the sensitivity analysis and the supportive exploratory endpoint of investigators’ assessments of clinical cure suggest non-inferiority for cadazolid compared with vancomycin on clinical response; however, as the primary endpoint was not met in these studies, there are no plans to further investigate cadazolid for the treatment of C. difficile infections,” they concluded.
The failure of cadazolid leaves metronidazole, vancomycin and fidaxomycin as the main treatments for C. difficile.
However frequent recurrence of disease following treatment highlights the area as one of unmet clinical need.
“Therapies for C. difficile infection are needed that cure a large proportion of patients, and sustain cure, particularly for cases caused by epidemic strains,” the study authors said.
Johnson & Johnson, the company that bought the rights to market cadazolid said: “a decision was made to discontinue further development of cadazolid in Phase 3 for the treatment of clostridium difficile-associated diarrhea.”