Treatment outcomes with rezafungin and caspofungin in people aged 65 years and above with candidaemia and/or invasive candidiasis: integrated analysis of pooled Phase 2 and Phase 3 data

Abstract Background Factors including frailty and multimorbidity can affect candidaemia and/or invasive candidiasis (C/IC) treatment in older people.1 The current analysis explored data from C/IC patients aged ≥65 years who were treated with rezafungin or caspofungin in the STRIVE (Phase 2: NCT02734862) and ReSTORE (Phase 3: NCT03667690) clinical trials.2,3 Methods STRIVE and ReSTORE were double-blind, randomized studies. Adults with C/IC, diagnosed by systemic signs and mycological confirmation, received rezafungin once-weekly (Week 1: 400 mg; Weeks 2–4: 200 mg) or once-daily caspofungin (Day 1: 70 mg; Days 2–28: 50 mg) by IV injection for ≥14 days (≤4 weeks). Post hoc analysis examined pooled STRIVE/ReSTORE data for subjects aged ≥65 years. Safety outcomes included treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) in subjects who received ≥1 dose of study drug (safety population). Day 30 all-cause mortality (ACM) and mycological response at Days 5 and 14 were examined for the modified intention-to-treat (mITT) population (subjects with mycological C/IC diagnosis within 96 h of randomization who received ≥1 study drug dose). Results The safety population included 132 subjects (rezafungin arm: 64; caspofungin arm: 68). The mITT population included 120 subjects (rezafungin arm: 57; caspofungin arm: 63). The most common TEAEs with rezafungin were hypokalaemia, diarrhoea, vomiting and anaemia (Table 1). Eight subjects reported rezafungin-related TEAEs and seven had caspofungin-related TEAEs. SAEs comprised one case each of first degree atrioventricular block (rezafungin arm) and acute liver injury (caspofungin arm). Day 30 ACM rate was 14.0% (rezafungin arm) and 31.7% (caspofungin arm). The between-group difference (95% CI) was -17.6 (−32.5, −2.8). Day 5 mycological response was 78.9% (rezafungin arm) and 58.7% (caspofungin arm; difference [95% CI]: 19.3 [3.3, 35.2]; Figure 1). Conclusions Integrated analysis of pooled STRIVE/ReSTORE study data revealed similar incidence of drug-related TEAEs and SAEs in patients aged ≥65 years treated with rezafungin or caspofungin. Further analyses are required to understand underlying factors influencing between-group differences regarding treatment outcomes.