Fidaxomicin, a macrocyclic antibiotic, was found noninferior to vancomycin against Clostridium difficile in a phase III noninferiority study reported in the Feb. 3 issue of the New England Journal of Medicine.
Fidaxomicin also had a significantly lower rate of recurrent infection than vancomycin, and the two agents had comparable adverse effect profiles, said Dr. Thomas J. Louie of the University of Calgary (Alta.) and his associates.
It was hoped that fidaxomicin, previously known as OPT-80, would prove to be a highly active but more selective therapy for C. difficile than is currently available. Dr. Louie and his colleagues compared it with vancomycin in a prospective international trial sponsored by the manufacturer, Optimer Pharmaceuticals. The study subjects were 629 adults randomly assigned in equal numbers to oral therapy at 52 sites in Canada and the United States.
The primary efficacy end point was the rate of clinical cure, or complete resolution of diarrhea. In the intention-to-treat analysis of 596 patients, 88% of patients taking fidaxomicin and 86% of those taking vancomycin met the criteria for clinical cure. In the per-protocol analysis of 548 patients, 92% of the patients taking fidaxomicin and 90% of those taking vancomycin attained a clinical cure.
Subgroup analyses in both populations showed that treatment response was similar between the two groups regardless of patient age, need for hospitalization, history of C. difficile infection, severity of disease at baseline, type of infecting strain, response to metronidazole treatment, or several other factors.
Fidaxomicin was associated with a significantly lower rate of recurrence in both the intention-to-treat population (15%) and the per-protocol population (13%) than was vancomycin (25% and 24%, respectively). This represents a 45% relative reduction in recurrences with fidaxomicin.
The recurrence rate was found to be similar between fidaxomicin and vancomycin among patients infected with the NAP1/BI/027 strain (the hypervirulent "North American" strain). However, the recurrence rate was significantly lower among patients with less virulent strains who took fidaxomicin (8%) than among those who took vancomycin (26%).
"This represents a 69% relative reduction in recurrences with fidaxomicin," the investigators said (N. Engl. J. Med. 2011 Feb. 3;364:422-31).
Decreases in recurrences are of obvious benefit to patients, and should reduce treatment costs as well. But another important benefit is that they also should reduce the rate of person-to-person transmission, Dr. Louie and his colleagues noted.
The median time until the resolution of diarrhea was shorter with fidaxomicin in both the intention-to-treat and per-protocol populations, but this difference did not meet statistical significance.
There were no significant differences between the two drugs in rates of adverse events, serious adverse events, or adverse events possibly related to the study treatment. No subjects discontinued the study because of intolerance or allergy to the drugs.
Taken together, these findings indicate that fidaxomicin and vancomycin "have similar effectiveness with respect to the clinical resolution of acute diarrheal disease due to C. difficile infection, but more sustained or durable resolution of disease (that is, improved global cure) is achieved with fidaxomicin," Dr. Louie and his associates said.
This study was funded by Optimer Pharmaceuticals. Dr. Louie and his associates reported being listed on a fidaxomicin patent and other patents, and reported ties to Merck, Cubist Pharmaceuticals, ViroPharma, Cempra, Iroko Pharmaceuticals, Salix Pharmaceuticals, Abbott, Bayer, Pfizer, and Genzyme.