Rezafungin is noninferior to caspofungin for the treatment of candidemia and invasive candidiasis, according to study results published in The Lancet.
This double-blinded, double-dummy, randomized phase 3 trial was conducted at 66 tertiary care centers across 15 countries between October 2018 and August 2021. Adults with mycologic-confirmed invasive candidiasis or candidemia were randomly assigned in a 1:1 fashion to receive either intravenous (IV) rezafungin once weekly or IV caspofungin once daily. The primary endpoints were global cure at day 14 and all-cause mortality at 30 days, both of which had a noninferiority margin of 20%. The sample size was based on a continuity-corrected Z-statistic. An unweighted Miettinem-Nurmien methodology was used to calculate a 2-sided 95% CI for differences in 30-day all-cause mortality rates between the treatments.
The intention-to-treat population included 199 patients, of whom 100 were in the rezafungin cohort and 99 were in the caspofungin cohort. Among patients in the rezafungin and capsofungin cohorts, 67% and 57% were men, 61% and 61% were White, 60% and 59% were younger than 65 years, 70% and 69% had candidemia, and 30% and 31% had invasive candidiasis, respectively.
At day 14, global cure was observed among 55 (57%) patients in the rezafungin cohort and 57 (61%) in the caspofungin cohort (weighted treatment difference, -1; 95% CI, -14.9 to 12.7). The rate of 30-day all-cause mortality was 24% and 21% among patients in the rezafungin and caspofungin cohorts, respectively (treatment difference, 2.4%; 95% CI, -9.7% to 14.4%).
In the safety analysis, 91% of patients in the rezafungin cohort and 85% of those in the caspafungin cohort experienced at least 1 treatment-emergent adverse event. The most common events were pyrexia, hypokalemia, pneumonia, septic shock, and anemia.
Limitations of this study were the exclusion of pediatric patients and those with certain forms of invasive candidiasis.
According to the researchers, “Future research of rezafungin treatment might investigate the clinical implications of early efficacy…”
Disclosure: This research was supported by Amplyx, Astellas, Cidra, F2G, and Manye.
Please see the original reference for a full list of disclosures.
Thompson GR, Soriano A, Cornely OA, et al; on behalf of the ReSTORE trial investigators. Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial. Lancet. Published online, November 25, 2022. doi:10.1016/s0140-6736(22)02324-8