Rezafungin

Summary

Rezafungin (CD101, Rezzayo) is a next‑generation echinocandin antifungal approved for prescription use. Administered intravenously, it is designed for once‑weekly dosing and targets invasive Candida infections such as candidaemia and invasive candidiasis. Its lipopeptide structure confers a long plasma half‑life, allowing a simplified regimen compared with daily echinocandins.

Mechanism of Action

Rezafungin is a semi‑synthetic cyclic lipopeptide that inhibits the fungal β‑(1,3)‑d‑glucan synthase enzyme. By blocking synthesis of β‑(1,3)‑d‑glucan, an essential cell‑wall polysaccharide, the drug weakens the cell wall and leads to osmotic instability and fungal cell death. This mechanism is shared with other echinocandins but rezafungin’s chemical modifications give it a prolonged half‑life.

What the Research Shows

The pivotal ReSTORE phase‑3 trial compared intravenous rezafungin (400 mg loading, then 200 mg weekly) with daily caspofungin in 199 adults with candidaemia or invasive candidiasis. Rezafungin achieved a global cure rate of 59% at day 14, non‑inferior to caspofungin’s 61%, and 30‑day all‑cause mortality of 24% versus 21%, meeting predefined non‑inferiority margins. Safety profiles were comparable; 91% of rezafungin recipients experienced at least one adverse event versus 85% with caspofungin, and serious events occurred in 56% versus 53%. Review articles highlight rezafungin’s once‑weekly dosing, broad activity against Candida and Aspergillus, and its recent FDA approval (March 2023) and EMA orphan‑drug status (2024).

Reported Benefits

Clinical data show rezafungin is non‑inferior to caspofungin for cure and mortality in invasive candidiasis, offering a comparable efficacy with a more convenient weekly infusion schedule. The extended half‑life reduces hospital visits and may facilitate outpatient therapy. Its activity against Candida spp and Aspergillus spp expands therapeutic options for infections where resistance to other agents is emerging.

Limitations of the Evidence

Evidence is currently limited to candidaemia and invasive candidiasis; data on other invasive mould infections are sparse. The ReSTORE trial noted the need for further evaluation of early‑treatment efficacy. Long‑term safety and real‑world effectiveness remain to be fully characterized, and head‑to‑head comparisons with agents beyond caspofungin are lacking.

Safety Considerations

Adverse events with rezafungin were similar to those seen with caspofungin. The most frequently reported events (≥5% of patients) included pyrexia, hypokalaemia, pneumonia, septic shock, and anaemia. Serious adverse events occurred in about 56% of participants, but no new safety signals emerged. Overall, the safety profile was considered acceptable, though clinicians should monitor for typical echinocandin‑related toxicities and laboratory abnormalities.

How It Is Administered

Rezafungin is supplied as an acetate formulation for intravenous infusion. The approved regimen involves a 400 mg loading dose followed by 200 mg administered once weekly, typically over a short infusion period. No oral formulation is available.

Routes of Administration

Goals & Uses

• Activity against echinocandin-resistant CandidaResistant Organism CoverageLow
• Invasive candidiasis treatmentAntifungalHigh
• Treatment of invasive candidiasisAntifungalHigh
• Candidemia treatmentInfectious DiseaseHigh
• Prophylaxis in neutropenic patientsPreventionModerate
• Treatment of candidemiaAntifungal TherapyHigh
• Antifungal prophylaxis in hematopoietic stem cell transplant recipientsProphylaxisModerate

Contraindications

• Severe hepatic impairment (Child‑Pugh C)Liver DiseaseModerate
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Known hypersensitivity to rezafungin or other echinocandinsAllergyHigh

Adverse Effects

• HypokalemiaElectrolyteCommon
• AnemiaHematologicCommonLow red blood cell count or hemoglobin
• Elevated liver enzymes (ALT/AST)HepaticUncommon
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• VomitingGastrointestinalCommonForceful expulsion of stomach contents
• Elevated liver enzymes (ALT, AST)HepaticUncommon
• Infusion‑related reactions (e.g., flushing, rash)GeneralCommon
• Infusion-related reactionsHypersensitivityUncommon

Drug Interactions

• CyclosporineLow
• Strong CYP3A4 inducers (e.g., rifampin)Moderate
• TacrolimusLow
• Azoles (e.g., fluconazole)Low

Population Constraints

• Pediatric patients (<18 years)AgeAbsolute
• Pediatric patientsAgeRelative
• Breastfeeding womenReproductiveRelative
• Pregnant or breastfeeding womenReproductiveRelative
• Pregnant womenReproductiveRelative
• Severe hepatic impairmentOrgan ImpairmentRelative

Regulatory Status

• European UnionInvestigationalEMA review ongoing; clinical trials completed.
• United StatesApprovedApproved: candidemia, invasive candidiasisFDA approval 2023; once‑weekly IV dosing.
• United KingdomUnknownPost-Brexit regulatory status not confirmed at time of knowledge cutoff

Approved by the FDA (2023) for invasive candidiasis and candidemia; under review in the EU.

Evidence & Sources

• An update on newer antifungals
  Journal ArticleModerateAkinosoglou K, et al.2025-01-01T00:00:00.000000Z
• Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial
  Journal ArticleModerateThompson GR 3rd, et al.2023-01-01T00:00:00.000000Z
• The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin
  Journal ArticleModerateHoenigl M, et al.2021-01-01T00:00:00.000000Z
• New treatment options for critically important WHO fungal priority pathogens
  Journal ArticleModerateKriegl L, et al.2025-01-01T00:00:00.000000Z
• Echinocandins - structure, mechanism of action and use in antifungal therapy
  Journal ArticleModerateSzymański M, et al.2022-01-01T00:00:00.000000Z

Frequently Asked Questions