Uses and advantages of Rezafungin

Rezafungin is a novel, once-weekly antifungal being developed for the treatment and prevention of serious fungal infections.Rezafungin is a member of the echinocandin class of drugs. Echinocandins are considered the safest antifungal drugs available and are suggested by the Infectious Disease Society of America (IDSA) as first-line treatment for fungal infections. Rezafungin’s structure and properties have been precisely refined to retain the safety benefits of echinocandin drugs while enhancing its pharmacokinetic and pharmacodynamic properties to create a longer-lasting, next-generation treatment and preventative, capable of addressing even drug-resistant species.

Uses

Rezafungin (CD-101) is a second generation echinocandin with a similar spectrum and mechanism of action. Along with fosmanogepix, ibrexafungerp, olorofim, and opelconazole, rezafungin heralds a new era in the treatment of fungal infections. 

Related research

Rezafungin is a structural analogue of anidulafungin. It is a cyclic hexapeptide with a lipophilic tail and a choline moiety at the C-5 ornithine position which enhances its stability. The changes in the structure influence increased chemical stability in plasma, aqueous solution, and at elevated temperature. The pharmacokinetic profile enables once-weekly intravenous formulation for the treatment and prophylaxis of systemic fungal infections. 

Rezafungin was compared to caspofungin in the STRIVE study, which was a double-blind phase-2 trial. Adult patients with candidaemia or invasive candidiasis were randomized to receive caspofungin (70 mg loading dose, then 50 mg) or rezafungin (400 mg per week, or 400 mg for the first week, then 200 mg per week) for a total duration of therapy of up to 4 weeks. Clinical cure, investigator-assessed clinical response, and survival were the endpoints of the trial. The cure rates were 67.2% for caspofungin, 60.5% for rezafungin 400 mg, and 76.1% (35/46) for rezafungin 400/200 mg. The 30-day all-cause mortality was 15.8% in patients on rezafungin 400 mg, 4.4% in patients on rezafungin 400/200 mg, and 13.1% in the caspofungin group. 

Clearance of candidaemia was achieved in 19.5 h in the rezafungin group and 22.8 h in caspofungin group.There were no safety issues identified during the conduct of the trial. The reason for the difference between the cure rates in the two rezafungin groups has no obvious explanation but it may be related to the structure of the trial e.g., the cure assessment category of ‘indeterminate’ when evaluating the outcome. Rezafungin has been investigated in murine models of Pneumocystis murina. Four weeks of rezafungin prevented the development of P. murina pneumonia in mice. Eight weeks of treatment led to abolition of established infection. Thus, rezafungin may hold promise for human infections with P. jirovecii. 

Advantages

Rezafungin may have advantages other than the favorable pharmacokinetic profile. Data suggest that the development of resistance is less likely with rezafungin, with a mutant prevention concentration of 16 mg/L i.e., at and above this level, selection of mutants is unlikely, a property it shares with other echinocandins. However, it might attain this concentration in tissues more readily and predictably which reduces the chances of selection of resistant fungal cells (Garcia-Effron, 2020). In a murine model of intra-abdominal candidiasis, rezafungin was shown to have superior penetration into tissue as compared to micafungin.