Iclaprim noninferior to vancomycin for acute bacterial skin infections

G. Ralph Corey

The investigational drug candidate iclaprim was well-tolerated in patients with acute bacterial skin and skin structure infections and achieved noninferiority compared with vancomycin, according to topline results from the phase 3 REVIVE-2 study announced October 4.

“[Acute bacterial skin and skin structure infection (ABSSSI)] is a serious infection for which patients are frequently hospitalized for several days,” G. Ralph Corey, MD, vice chair for education and global health and Gary Hock Professor at Duke University School of Medicine, Durham, N.C., said in a press release. “Many of these patients have comorbidities, such as renal impairment and diabetes. For these patients in particular, there is an urgent need for better treatment options.”

Researchers conducted the REVIVE-2 trial, a double-blind, active-controlled, global study including 600 patients with ABSSSI to determine the safety and efficacy of an 80 mg IV dose of iclaprim compared with a 15 mg/kg IV dose of vancomycin. Participants received treatments every 12 hours for 5 to 14 days.

In the intent-to-treat population, iclaprim was noninferior (10% margin) to vancomycin at 48 to 72 hours after the initiation of administration (early time point), which was the primary endpoint. Early clinical response, which was defined as a greater than or equal to 20% reduction of lesion area at 48 to 72 hours, at early time point, was observed in 78.3% of patients treated with iclaprim, and 76.7% of patients treated with vancomycin (treatment difference, 1.58%; 95% CI, -5.10%, 8.26%). Iclaprim was also non-inferior to vancomycin in the intent-to-treat population 7 to 14 days after discontinuation of the drug (test of cure endpoint), with a total of 78.0% of patients receiving iclaprim and 77.7% of patients receiving vancomycin demonstrating clinical cure (treatment difference, 0.26%; 95% CI, -6.39%, 6.91%).

In an analysis of a pre-specified secondary endpoint, resolution or near resolution at end of therapy was observed in 54.6% of patients receiving iclaprim and 55.4% of patients receiving vancomycin (treatment difference, −0.83%; 95% CI, −8.80% to 7.13%). In another pre-specified secondary endpoint analysis, using a modified clinical cure test of cure endpoint which was defined as a greater than or equal to 90% reduction in lesion size at the test of cure time point, having a lesion that did not increase in size since the early time point and not requiring additional antibiotics, clinical cure was seen in 71.9% of patients receiving iclaprim and 70.5% of patients receiving vancomycin (treatment difference, 1.37%, 95% CI -5.88% to 8.62%). In addition, iclaprim was well-tolerated and adverse events were mostly mild.

“Iclaprim is a special drug with unique attributes,” Corey, who was also principal investigator of REVIVE-2, told Healio Internal Medicine. “It has a fixed dose, so the same dose can be given when dealing with smaller or bigger people, which makes it much easier for the clinician. Iclaprim has no renal toxicity, so clinicians can give it to patients with mild renal dysfunction without worrying that they are going to make that worse, as opposed to vancomycin where we have problems with its nephrotoxicity, especially in patients who already have mild renal dysfunction. Furthermore, iclaprim is the not like Bactrim/Septra, which can cause both renal toxicity and a significant incidence of allergic reactions to the drug. This drug is easy to use for clinicians, is very effective and would fit well in our armamentarium.” – by Alaina Tedesco

Disclosure: Corey is the principal investigator of REVIVE-2.