The drug met its primary endpoint of noninferiority to vancomycin at both 48 to 72 hours after drug initiation and test of cure.
Iclaprim, a diaminopyrimidine antibiotic developed by MotifBio, proved safe and effective in a phase 3 trial for the treatment of patients with acute skin and skin structure infections (ABSSSI). The drug met its primary endpoint of noninferiority to vancomycin at both 48 to 72 hours after initiation and test of cure.
These results were presented at the 28th European Congress of Clinical Microbiology and Infectious Diseases, (ECCMID) held in Madrid, Spain.
According to MotifBio, iclaprim is a “targeted Gram-positive antibiotic” that works in a way that differs from most antibiotics on the market in that it is able to quickly kill bacteria in vitro.
In an interview with Contagion®, William D. O’Riordan, MD, FACEP, chief medical officer at eStudySite, explained what makes iclaprim so unique in the treatment of ABSSSIs, among the most common infections providers face in community and hospital settings.
“It has a very unique mechanism of action where, in the future—and we can’t say conclusively, but it will be very difficult because of its 2 mechanisms—for resistance to occur. I think that is a unique feature of this antibiotic,” he said. “It interferes with dihydrofolate reductase, which is intimately involved with the bacterial cell and the cell integrity and does away with the cell itself.”
For REVIVE-2, a phase 3, double-blind, multinational trial, investigators sought to prove that iclaprim is as safe and effective as vancomycin for the treatment ABSSSIs. A total of 600 patients were enrolled in the trial. Investigators compared the safety and effectiveness of iclaprim 80mg with vancomycin 15mg/kg, which were both given every 12 hours for 5 to 14 days, intravenously.
“The primary endpoint of this study was to determine whether iclaprim was non-inferior (NI; 10% margin) to vancomycin in achieving a ≥20% reduction in lesion size (early clinical response [ECR]) at 48 to 72 hours after initiation of the study drug (ETP), compared to baseline in the intent-to-treat (ITT) population,” abstract authors write.
For the trial’s secondary endpoint, the investigators sought to prove that iclaprim was noninferior to vancomycin in the ITT population at the test of cure visit, which occurred about 1 to 2 weeks after study drug completion.
“A modified clinical cure TOC (MTOC) was defined by a ≥90% reduction in lesion size at TOC, no increase in lesion size since ETP and no requirement for additional antibiotics,” according to the study authors.
Investigators reported that a clinical cure was found in 71.5% of those who received iclaprim compared with a 70.5% clinical cure seen in those who had been receiving vancomycin at the MTOC. The drug proved to be well-tolerated as most of the adverse events reported were classified as mild, and the rate at which drug-associated adverse events emerged was 14% for iclaprim and 12.9% for vancomycin.
Overall, REVIVE-2 demonstrated that iclaprim was safe and effective for the treatment of patients with ABSSSIs. The drug met its primary endpoint of noninferiority at ETP and TOC, with a low rate of associated adverse events.
In a past press release on the results of the previous phase 3 trial, REVIVE-1, MotifBio representatives commented that if REVIVE-2 proved successful, the company would file a new drug application (NDA).
"Following the positive outcome in this clinical trial, the differentiated mechanism, potency, spectrum, safety and efficacy of iclaprim, if approved, could provide a valuable new antibiotic treatment option that is urgently needed to offset the rising problem of bacterial resistance,” Dr. O'Riordan stressed in a recent statement.