Drug Update · Infectious Disease

FDA Approves Rezafungin for Candidemia/IC: Day 30 Mortality 23.7% vs 21.3%

September 11, 2026

Day 30 all-cause mortality (mITT)

REZZAYO 23.7% vs caspofungin 21.3% (difference 2.4%; 95% CI -9.7, 14.4)

Recommended dosing

400 mg IV loading dose on Day 1, then 200 mg IV once weekly

Label effective date

2026-07-01

Original FDA approval date

2023-03-22

Clinical Perspective

Infectious disease specialists, hospitalists, pharmacists, and outpatient parenteral antimicrobial therapy programs treating adults and pediatric patients 12 years and older with candidemia and invasive candidiasis who have limited or no alternative options are the primary audience for this label update ^[2]^[6]. The FDA approval is supported by the ReSTORE randomized noninferiority trial showing Day 30 all-cause mortality of 23.7% with REZZAYO versus 21.3% with caspofungin, and the labeling specifies a once-weekly IV regimen (400 mg loading, then 200 mg weekly) with safety not established beyond four weekly doses ^[6]^[4]. An open clinical question remains: what are the safety and efficacy outcomes with REZZAYO when treatment extends beyond four weekly doses in real-world practice?

Dr. Simran Kohli, MBBS, MD (General Medicine), DM (Infectious Diseases) · Infectious Diseases

The FDA has approved rezafungin (REZZAYO) for the treatment of candidemia and invasive candidiasis, with updated labeling effective July 1, 2026 and a most recent supplemental approval date of July 16, 2026 ^[6]^[2]. The approval covers patients 12 years of age and older who have limited or no alternative options and is supported by the phase 3 ReSTORE trial, in which Day 30 all-cause mortality was 23.7% with REZZAYO versus 21.3% with caspofungin (difference 2.4%; 95% CI -9.7, 14.4) ^[6]^[4].

Clinical Context

Rezafungin (REZZAYO) is an echinocandin antifungal agent developed for intravenous use and manufactured by Melinta Therapeutics / Cidara/Melinta-associated sponsors as reflected in the prescribing information and regulatory summaries ^[1]^[3]^[6]. The agent supports once-weekly intravenous dosing via an initial 400 mg loading dose followed by 200 mg once weekly thereafter, and the safety of dosing beyond four weekly doses has not been established in the provided excerpts ^[1]^[6]. Clinicians should consult current prescribing information for full dosing guidance. The FDA approval was based on limited clinical safety and efficacy data in patients with candidemia and invasive candidiasis and excludes evaluation for endocarditis, osteomyelitis, and meningitis due to Candida in the available labeling ^[1]^[6]. Regulatory reviewers noted that weekly dosing enables outpatient parenteral treatment that potentially avoids the need for a central venous catheter, a point discussed in postapproval regulatory commentary ^[5].

Key Findings

The ReSTORE phase 3 randomized, double-blind, active-controlled noninferiority trial showed Day 30 all-cause mortality of 23.7% with REZZAYO 400 mg/200 mg versus 21.3% with caspofungin 70 mg/50 mg (difference 2.4%; 95% CI -9.7, 14.4) in the modified intent-to-treat population, which supported noninferiority and the FDA approval ^[6]^[4].
Clinicians should consult current prescribing information for full dosing guidance.
Global cure (mycological eradication/presumed eradication, clinical cure, and radiologic cure for IC) at Day 14 was 59.1% with REZZAYO versus 60.6% with caspofungin (difference -1.5%; 95% CI -15.4, 12.5) in Trial 1 ^[6].
Day 5 mycological eradication in Trial 1 was 68.8% with REZZAYO versus 61.7% with caspofungin (difference 7.1%; 95% CI -6.6, 20.6) as reported in the prescribing information ^[6].
The FDA Drug Trials Snapshot and the prescribing information report 199 patients randomized in Trial 1 with the mITT population comprising 187 culture-positive patients who received at least one dose of study drug; a pooled safety database incorporated results from Trial 2 for supportive safety assessment ^[4]^[6].

Safety & Tolerability

Most common adverse reactions (incidence ≥ 5%) listed in the REZZAYO labeling include hypokalemia, pyrexia, diarrhea, anemia, vomiting, nausea, hypomagnesemia, abdominal pain, constipation, and hypophosphatemia ^[1]^[6].
Infusion-related reactions including flushing, sensation of warmth, urticaria, nausea, and chest tightness have been observed; if these occur, the infusion may be slowed or paused ^[1]^[6].
Cases of hypersensitivity reactions, including anaphylaxis, have been reported in postmarketing experience ^[2]^[3].
Hepatic adverse reactions and abnormalities in liver tests have been seen in clinical trial patients treated with REZZAYO; clinicians are advised that abnormalities in liver tests have occurred and to evaluate risk/benefit of continuing therapy in such cases ^[1]^[6].

Study Design

The efficacy claim supporting approval came from Trial 1 (ReSTORE; NCT03667690), a multicenter, randomized, double-blind, active-controlled noninferiority trial that randomized 199 patients 1:1 to REZZAYO or caspofungin with randomization stratified by diagnosis and APACHE II/ANC at screening; the primary efficacy endpoint was Day 30 all-cause mortality in the mITT population ^[6]^[4]. Patients in the REZZAYO arm received a single 400 mg loading dose on Day 1 followed by 200 mg once weekly for a total of two to four doses; patients in the caspofungin arm received a 70 mg loading dose followed by 50 mg once daily for 2 to 4 weeks, with the option after ≥3 days to step down to oral fluconazole when criteria for cure and discharge planning were met ^[6]. Clinicians should consult current prescribing information for full dosing guidance. Trial 2 was a supportive exploratory study used mainly for safety; pooled safety data were used to characterize adverse reactions ^[6].

FAQ

Q1 What is rezafungin (REZZAYO) approved for?

REZZAYO is indicated for the treatment of candidemia and invasive candidiasis in adults and pediatric patients 12 years of age or older who have limited or no alternative options. The approval is based on limited clinical safety and efficacy data from randomized trials including the phase 3 ReSTORE trial. The label notes that REZZAYO has not been studied for Candida endocarditis, osteomyelitis, or meningitis in the provided excerpts.

Q2 How does rezafungin work?

Rezafungin is an echinocandin antifungal agent. The prescribing information describes rezafungin as an echinocandin with antifungal activity against Candida species; mechanistic and microbiology sections are included in the full labeling but mechanistic detail beyond class identification was not excerpted in the provided summaries.

Q3 What is the recommended dose of rezafungin (REZZAYO)?

The recommended intravenous dosing regimen in the labeling is a single 400 mg loading dose on Day 1 followed by 200 mg administered once weekly thereafter. The safety of REZZAYO has not been established beyond four weekly doses in the provided excerpts. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of rezafungin?

Most common adverse reactions reported at an incidence ≥ 5% include hypokalemia, pyrexia, diarrhea, anemia, vomiting, nausea, hypomagnesemia, abdominal pain, constipation, and hypophosphatemia. Infusion-related reactions and abnormalities in liver tests were observed in clinical trials, and serious hypersensitivity including anaphylaxis has been reported postmarketing. For full safety information, consult the complete prescribing information.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves Rezafungin for Candidemia/IC: Day 30 Mortality 23.7% vs 21.3%

Direct Clinical Takeaway & Evidence Summary

FDA Approves Rezafungin for Candidemia/IC: Day 30 Mortality 23.7% vs 21.3%

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

Cite & Reference This Monograph

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