CD101, a novel echinocandin with long-acting pharmacokinetics and chemical stability, is being developed as an IV, once-weekly administered antifungal for serious fungal infections. CD101 IV is currently in clinical development for the treatment of candidemia. Given the potent in vitro activity of CD101 against A. fumigatus, this study was conducted to evaluate the in vivo efficacy of CD101 IV for treatment of aspergillosis using a disseminated infection model in neutropenic mice.
The susceptibility of the A. fumigatus test strainATCC 13073 was evaluated by measuring the minimal effective concentration (MEC) for changes in the hyphal morphology (CLSI protocol M38-A2). The in vivo efficacy was assessed using a mouse model of disseminated aspergillosis in which neutropenic animals were infected by injecting a suspension of A. fumigatus strain ATCC 13073 into the tail vein with an inoculum size of 104 CFU/mouse. Test article and vehicle were administered to groups of 10 mice twice daily by IV injection starting 2 h after infection for five days (BID×5). Survival was monitored for 10 days after infection. The Fisher’s exact test was performed to assess the significance of the differences between the test article and vehicle treatment groups.
CD101 demonstrated potent in vitro activity against A. fumigatus strain ATCC 13073 with an MEC value of 0.0078 μg/ml. CD101 administered IV to infected neutropenic mice at 0.2, 1 and 5 mg/kg BID for 5 days was associated with a significant increase in 10-day survival compared to vehicle group (p < 0.05; Figure). Amphotericin B was used as the positive control treatment at 0.3 mg/kg BID for 5 days. Animal survival rate of CD101 at the lowest dose tested, 0.2 mg/kg, was comparable to amphotericin B at 0.3 mg/kg.
CD101 IV was shown to be effective when administered by the IV route, using a mouse model of disseminated A. fumigatus infection. The efficacy supports the utility of CD101 IV for the treatment of aspergillosis.