Overcoming the Resistance Hurdle: PK-PD Target Attainment Analyses of Rezafungin (CD101) for Candida albicans and Candida glabrata [PublishAheadOfPrint]

Rezafungin (CD101) is a novel echinocandin antifungal agent with activity against Aspergillus and Candida species, including azole- and echinocandin-resistant isolates. The objective of these analyses was to conduct pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses to evaluate single and once-weekly rezafungin dosing to provide dose selection support for future clinical studies. Using a previously developed rezafungin population PK model, Monte Carlo simulations were conducted utilizing the following three IV rezafungin dosing regimens: (i) single 400-mg dose, (ii) 400 mg for Week 1 followed by 200 mg weekly for 5 weeks, and (iii) 400 mg weekly for 6 weeks. Percent probabilities of achieving the non-clinical PK-PD targets associated with net fungal stasis and 1-log₁₀ CFU reductions from baseline for Candida albicans and Candida glabrata were calculated for each rezafungin dosing regimen. At the MIC₉₀ for C. albicans and C. glabrata, single dose rezafungin 400 mg achieved probabilities of PK-PD target attainment ≥90% through Week 3 of therapy for all PK-PD targets evaluated. When evaluating the multiple dose (i.e., weekly) regimens under these conditions, percent probabilities of PK-PD target attainment of 100% were achieved through Week 6. Moreover, high (>90%) probabilities of PK-PD target attainment were achieved through Week 6 following administration of the weekly dosing regimens at or above the MIC₁₀₀ values for C. albicans and C. glabrata based on contemporary in vitro surveillance data. These analyses support the use of single and once-weekly rezafungin dosing regimens for the treatment of patients with candidemia and/or candidiasis due to C. albicans or C. glabrata.

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