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Rezafungin (Rezzayo)
Rezafungin is a real, FDA-approved fourth echinocandin, joining this site's caspofungin/micafungin/anidulafungin page with the same fungal-only glucan-synthase mechanism — but chemically modified to resist breakdown, allowing once-weekly IV dosing instead of daily. Its March 2023 approval is a genuinely narrower one than its three older siblings: a single pivotal trial rather than the customary two, and a restricted "limited or no alternative treatment options" label, after the FDA flagged a nonclinical neurotoxicity signal and required a larger pooled safety database before clearing it.
On this page
In brief
Should you care? Relevant only in the context of serious invasive Candida infections — a hospital-only antifungal with no wellness or grey-market presence, but a genuinely interesting case of a narrower FDA approval than its own drug class predecessors.The short version
- FDA-approved 22 March 2023 (Rezzayo, Cidara Therapeutics/Melinta Therapeutics) for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.
- The ReSTORE trial (Thompson et al., 2023) found once-weekly rezafungin noninferior to daily caspofungin on Day 30 all-cause mortality: 25.2% vs. 24.8% (treatment difference 0.4%, 95% CI -10.8 to 11.6).
- Approved on a single pivotal trial, after the FDA required a larger pooled safety database over a nonclinical neurotoxicity signal flagged in 2021.
A fourth echinocandin, engineered for once-weekly dosing
Rezafungin is a semisynthetic derivative of anidulafungin, one of the three echinocandins this site's echinocandins page already covers, and it works the same way: blocking 1,3-β-D-glucan synthase, the enzyme fungi use to build their cell walls, a target human cells simply don't have. What's different is a structural modification to the molecule's tail that dramatically slows its breakdown, extending its half-life to roughly 80 hours versus 24-27 hours for caspofungin, micafungin and anidulafungin. That change is what allows rezafungin to be dosed once a week (a 400mg loading dose in week one, then 200mg weekly) instead of once a day — potentially avoiding a permanent central venous catheter for some outpatients, since a once-weekly infusion is far more compatible with peripheral-line or outpatient parenteral therapy than a daily one.
ReSTORE: noninferior to caspofungin on 30-day mortality
Rezafungin's approval rested primarily on ReSTORE (Thompson GR 3rd, Soriano A, Skoutelis A, et al., Lancet 2023;401(10370):49-59, PMID 36442484, DOI: 10.1016/S0140-6736(22)02324-8), a global, double-blind, double-dummy Phase 3 trial across 66 centers in 15 countries. Adults with candidemia or invasive candidiasis were randomized to once-weekly IV rezafungin or once-daily IV caspofungin for up to 4 weeks. On the primary endpoint, Day 30 all-cause mortality, rezafungin was noninferior to caspofungin: 25.2% versus 24.8% (treatment difference 0.4%, 95% CI -10.8 to 11.6), comfortably inside the trial's predefined 20-percentage-point noninferiority margin. A supporting Phase 2 trial, STRIVE, had shown a similar pattern on a smaller scale.
Why the FDA narrowed the label
Caspofungin, micafungin and anidulafungin each carry a standard candidemia/invasive-candidiasis indication, typically supported by more than one dedicated trial. Rezafungin's FDA approval on 22 March 2023 rested on a single adequate and well-controlled Phase 3 study, and it carries a narrower "limited or no alternative treatment options" indication rather than the broader label its predecessors hold. That narrower framing traces to a real regulatory concern, not just trial-count arithmetic: FDA briefing documents show the agency, in a 2021 meeting with the sponsor, flagged a nonclinical neurotoxicity signal and asked for a larger pooled safety database — at least 300 candidemia/invasive-candidiasis patients exposed to rezafungin at the proposed dose — before it would proceed. Meeting that bar was complicated by real enrollment shortfalls: Phase 3 enrollment ran at roughly half the Phase 2 rate, worsened by COVID-19-era trial disruption. The eventual approval pooled ReSTORE and STRIVE safety data to clear the FDA's requested threshold.
Not the same review path as its class predecessors
A single-trial approval with a restricted "limited population" indication is a real, meaningfully narrower regulatory outcome than caspofungin, micafungin or anidulafungin received — worth knowing if you see rezafungin's label described as equivalent to the rest of its drug class.
Current status
Rezafungin has been commercially available in the US since its 2023 approval. Cidara Therapeutics, which developed it, licensed US commercial rights to Melinta Therapeutics in July 2022 (up to $460 million in potential payments) while retaining rights in Japan; Mundipharma holds commercial rights in the rest of the world, taking over that role in April 2024. CorMedix Inc. completed its acquisition of Melinta Therapeutics on 2 September 2025, making Rezzayo's US rights a CorMedix asset. A further Phase 3 trial testing rezafungin as antifungal prophylaxis in adult allogeneic stem-cell transplant recipients — a broader, non-restricted use — is expected to complete in the first half of 2026.
References
- Thompson GR 3rd, Soriano A, Skoutelis A, et al., "Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial," Lancet 2023;401(10370):49-59, PMID 36442484, DOI: 10.1016/S0140-6736(22)02324-8.
- FDA approval of Rezzayo (rezafungin for injection), 22 March 2023, for candidemia and invasive candidiasis in adults with limited or no alternative treatment options; FDA briefing document, NDA 217417.
- Cidara Therapeutics / Melinta Therapeutics license agreement, 26 July 2022 (SEC filings); CorMedix Inc. completed acquisition of Melinta Therapeutics, 2 September 2025 (SEC filing/press release).