| Description: |
Background STRIVE was conducted to assess the safety and efficacy of rezafungin (RZF), a novel echinocandin with pharmacokinetics allowing once weekly dosing and high, front-loaded plasma drug exposure, and to help determine dosing for a Phase 3 study. Methods Adults (≥18 years) with mycologically confirmed candidemia and/or invasive candidiasis (IC) were randomized (1:1:1) to receive RZF IV for up to 4 weeks dosed at either 400 mg weekly (Group 1) or 400 mg on week 1 and 200 mg weekly thereafter (Group 2), or standard of care (SOC; daily caspofungin [CSP] with optional criteria-defined oral stepdown after ≥3 days of IV therapy; Group 3). Safety and efficacy were evaluated by treatment-emergent adverse events (TEAEs) and overall success at day 14 (1° endpoint; clinical cure + mycological success), investigator assessment of clinical cure, mycological success (in subjects with candidemia only), overall success in IC subjects only, and mortality. Outcomes at day 5 were also assessed. Results The rate of TEAEs was 88.6% in Group 1, 94.4% in Group 2, and 81.8% in Group 3. Severe AEs occurred in 37.1%, 27.8%, and 39.4% of the groups, respectively. There were no concerning trends in System Organ Class groups, specific AEs, or laboratory abnormalities. The most common Candida species isolated was C. albicans (n = 45), followed by C. glabrata (n = 17), C. tropicalis (n = 15), and C. parapsilosis (n = 13). A high number of indeterminate responses due to missing data points in Group 1 led to analyses including and excluding the indeterminate responses. Overall, clinical, and mycological response rates at day 14 are shown in Table 1. Overall response at day 5 (Table 2) was highest in the RZF 400 mg/200 mg group, followed by the RZF 400 mg/400 mg and SOC groups. The overall mortality rate was 15.2% in Group 1, 9.7% in Group 2, and 17.9% in Group 3. Conclusion RZF demonstrated safety and efficacy comparable to CSP in the treatment of candidemia/IC. There were no concerning trends in AEs. The efficacy rates were ... |