Identification
- Summary
Rezafungin is an echinocandin antifungal indicated in patients over 18 years old who have limited or no alternative options for the treatment of candidemia and invasive candidiasis.
- Brand Names
- Rezzayo
- Generic Name
- Rezafungin
- DrugBank Accession Number
- DB16310
- Background
Rezafungin is an echinocandin antifungal drug.1,5 Unlike other echinocandins such as caspofungin and micafungin, rezafungin has long‐acting pharmacokinetics and a high stability that allows for it to have long dosing intervals maintaining high plasma exposure. Rezafungin has a half-life higher than 130 hours and can be administered once a week instead of daily. It can only be administered intravenously but does not reach therapeutic concentrations in the central nervous system, eye and urine.1,2 Rezafungin is active against Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis, as well as other Candida and Aspergillus spp.2,5
Clinical studies have shown that rezafungin is non-inferior to caspofungin for the treatment of candidaemia and invasive candidiasis.3 In March 2023, the FDA approved rezafungin for injection for the treatment of candidemia and invasive candidiasis in adults with limited or no alternative treatment options.5,6
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Rezafungin (DB16310)
- Weight
- Average: 1226.411
Monoisotopic: 1225.602719729 - Chemical Formula
- C63H85N8O17
- Synonyms
- Biafungin
- Echinocandin B, 1-((4R,5R)-4-hydroxy-N2-((4''-(pentyloxy)(1,1':4',1''-terphenyl)-4-yl)carbonyl)-5-(2-(trimethylammonio)ethoxy)-l-ornithine)-4-((4S)-4-hydroxy-4-(4-hydroxyphenyl)-l-allothreonine)-
- Rezafungin
- Rezafungin cation
- Rezafungin ion
- External IDs
- CD-101
- CD101
- SP-3025
Pharmacology
- Indication
Rezafungin is indicated in patients 18 years of age or older who have limited or no alternative options for the treatment of candidemia and invasive candidiasis.5
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Candidemia •••••••••••• ••••••• •• •• ••••••••••• ••••••••• ••••••• ••••••••• Treatment of Candidiasis, invasive •••••••••••• ••••••• •• •• ••••••••••• ••••••••• ••••••• ••••••••• - Contraindications & Blackbox Warnings
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Clinical studies showed that with the recommended dosage regimen, rezafungin exposure is on the plateau of the exposure-efficacy response curve. At a dose 3.5 times the maximum approved recommended loading dose, rezafungin did not lead to a clinically relevant QTc interval prolongation.5 The use of rezafungin is associated with infusion-related reactions, photosensitivity and hepatic adverse reactions.5
- Mechanism of action
Rezafungin is an echinocandin antifungal drug. It inhibits the 1,3-β-D-glucan synthase enzyme complex present in the cell walls of fungi, responsible for the formation of 1,3-β-D-glucan. Since 1,3-β-D-glucan is an essential component of fungal cell walls, rezafungin disrupts the cell wall of fungal species, including Candida spp., and acts as a concentration-dependent in vitro fungicidal. Mammalian cells do not express β-1-3-glucan synthase; therefore, the action of rezafungin is specific to fungi.5
Target Actions Organism A1,3-beta-glucan synthase component FKS1 inhibitorAspergillus niger (strain CBS 513.88 / FGSC A1513) A1,3-beta-glucan synthase component GSC2 inhibitorBaker's yeast - Absorption
Between 50 mg (0.125 times the approved maximum recommended loading dose) and 400 mg and with single or multiple doses, the Cmax and AUC of rezafungin increase in a dose-proportional manner. In patients with candidemia and invasive candidias given an initial 400 mg loading dose of rezafungin, followed by a 200 mg dose once weekly, the Cmax, AUC from time zero to 168 hours post-dose (AUC0-168) and Cmin on day 1 were 19.2 mcg/mL, 827 mcg⋅h/mL and 2.4 mcg/mL, respectively. In the same group of patients, the Cmax, AUC0-168 and Cmin on day 15 were 11.8 mcg/mL, 667 mcg⋅h/mL and 2.2 mcg/mL, respectively. Compared to healthy subjects, the AUC0-168 and Cmax were 30% and 19% lower in patients with candidemia. Age, sex, race, weight and hepatic impairment did not have a clinically significant effect on rezafungin pharmacokinetics.5
- Volume of distribution
Rezafungin has a volume of distribution of 67 L.5
- Protein binding
Rezafungin is highly protein bound. Protein binding goes from 87.5% to 93.6% in patients, and from 95.6% to >98.6% in healthy adults.5
- Metabolism
Rezafungin is metabolized by hydroxylation of the terphenyl, pentyl ether side chain, to form three hydroxylated metabolite isomers: 2’-, 3′-, or 4’-hydroxylpentyl rezafungin. Rezafungin can also be metabolized through a reaction that involves the loss of the pentyl group via O-dealkylation, forming despentyl-rezafungin. There is minimal subsequent conjugation (sulfation) of the hydroxyl metabolites.4 Rezafungin is not metabolized in the liver and is not expected to be a clinically relevant substrate of CYP450 enzymes.5
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- Route of elimination
Rezafungin is mainly eliminated through fecal excretion. In healthy subjects, 74.3% was recovered in feces primarily as rezafungin, while 25.7% was recovered in urine primarily as inactive metabolites of rezafungin.5
- Half-life
Rezafungin has a terminal half-life of 152 hours.5
- Clearance
Rezafungin has an elimination clearance of 0.35 L/hr.5
- Adverse Effects
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During clinical studies, no cases of rezafungin overdose were reported. Since rezafungin is highly protein bound, it is not anticipated to be dialyzable. In non-clinical studies, rezafungin did not show evidence of mutagenicity in a standard battery of assays, and did not affect mating or fertility in male or female rats given up to 45 mg/kg of rezafungin intravenously (6 times the clinical exposure) every 3 days. At doses greater or equal than 30 mg/kg of rezafungin, male mice presented lower sperm motility, and at 45 mg/kg, they had mild/moderate hypospermia and no detectable motile sperm. In rats given 45 mg/kg of rezafungin intravenously every 3 days for 3 months, males showed minimal tubular degeneration/atrophy in the testes and cellular debris in the epididymides at the end of the study. The carcinogenicity of rezafungin has not been evaluated in non-clinical studies.5
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Rezzayo Injection, powder, lyophilized, for solution 200 mg/1 Intravenous Melinta Therapeutics, LLC 2023-06-09 Not applicable US 
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Candida albicans and other yeasts
Chemical Identifiers
- UNII
- G013B5478J
- CAS number
- 1396640-59-7
- InChI Key
- LNFCWEXGZIEGJW-TXSVMFMRSA-O
- InChI
- InChI=1S/C63H84N8O17/c1-8-9-10-28-87-45-25-21-40(22-26-45)38-13-11-37(12-14-38)39-15-17-42(18-16-39)56(80)64-46-31-48(76)61(88-29-27-71(5,6)7)68-60(84)52-53(77)34(2)32-70(52)63(86)50(36(4)73)66-59(83)51(55(79)54(78)41-19-23-43(74)24-20-41)67-58(82)47-30-44(75)33-69(47)62(85)49(35(3)72)65-57(46)81/h11-26,34-36,44,46-55,61,72-73,75-79H,8-10,27-33H2,1-7H3,(H5-,64,65,66,67,68,74,80,81,82,83,84)/p+1/t34-,35+,36+,44+,46-,47-,48+,49-,50-,51-,52-,53-,54-,55-,61+/m0/s1
- IUPAC Name
- (2-{[(3S,4E,6S,7E,9S,11R,15S,16E,18S,20R,21R,22E,24S,25S,26S)-6-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-5,8,11,17,20,23,25-heptahydroxy-18-[(Z)-[hydroxy({4-[4'-(pentyloxy)-[1,1'-biphenyl]-4-yl]phenyl})methylidene]amino]-3,15-bis[(1R)-1-hydroxyethyl]-26-methyl-2,14-dioxo-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0^{9,13}]heptacosa-4,7,16,22-tetraen-21-yl]oxy}ethyl)trimethylazanium
- SMILES
- [H][C@](C)(O)[C@]1([H])\N=C(O)/[C@]([H])(C[C@@]([H])(O)[C@@]([H])(OCC[N+](C)(C)C)\N=C(O)/[C@@]2([H])N(C[C@]([H])(C)[C@]2([H])O)C(=O)[C@@]([H])(\N=C(O)/[C@@]([H])(\N=C(O)/[C@]2([H])C[C@@]([H])(O)CN2C1=O)[C@]([H])(O)[C@@]([H])(O)C1=CC=C(O)C=C1)[C@@]([H])(C)O)\N=C(/O)C1=CC=C(C=C1)C1=CC=C(C=C1)C1=CC=C(OCCCCC)C=C1
References
- Synthesis Reference
Hughes, D., et al. (2022). Synthesis of echinocandin antifungal agent. (U.S. Patent No. 11,524,980 B2). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/34/d5/c2/1a8cdcfb3fe3db/US11524980.pdf
- General References
- Lamoth F: Novel Therapeutic Approaches to Invasive Candidiasis: Considerations for the Clinician. Infect Drug Resist. 2023 Feb 22;16:1087-1097. doi: 10.2147/IDR.S375625. eCollection 2023. [Article]
- Miesel L, Lin KY, Ong V: Rezafungin treatment in mouse models of invasive candidiasis and aspergillosis: Insights on the PK/PD pharmacometrics of rezafungin efficacy. Pharmacol Res Perspect. 2019 Nov 20;7(6):e00546. doi: 10.1002/prp2.546. eCollection 2019 Dec. [Article]
- Thompson GR 3rd, Soriano A, Cornely OA, Kullberg BJ, Kollef M, Vazquez J, Honore PM, Bassetti M, Pullman J, Chayakulkeeree M, Poromanski I, Dignani C, Das AF, Sandison T, Pappas PG: Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial. Lancet. 2023 Jan 7;401(10370):49-59. doi: 10.1016/S0140-6736(22)02324-8. Epub 2022 Nov 25. [Article]
- Ong V, Wills S, Watson D, Sandison T, Flanagan S: Metabolism, Excretion, and Mass Balance of [(14)C]-Rezafungin in Animals and Humans. Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0139021. doi: 10.1128/AAC.01390-21. Epub 2021 Oct 18. [Article]
- FDA Approved Drug Products: REZZAYO (rezafungin) injection for intravenous use (March 2023) [Link]
- Globe News Wire: Cidara Therapeutics and Melinta Therapeutics Announce FDA Approval of REZZAYO (rezafungin for injection) for the Treatment of Candidemia and Invasive Candidiasis [Link]
- External Links
- ChemSpider
- 76713472
- 2639155
- ChEMBL
- CHEMBL3989945
- Wikipedia
- Rezafungin
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Candidemia / Fungal Infections / Invasive Candidiasis 1 3 Recruiting Prevention Aspergillus / Candidemia / Fungaemia / Fungal Infections / Invasive Candidiasis / Invasive Fungal Infections / Mold Infection / Pneumocystis / Prophylaxis Of Invasive Fungal Infections 1 2 Completed Treatment Candidemia / Fungaemia / Fungal Infections / Invasive Candidiasis 1 2 Completed Treatment Fungal Infections / Moniliasis, Vulvovaginal / Vaginitis, Monilial / Vulvovaginal Candidiasis / Yeast Infections 1 1 Completed Treatment Healthy Volunteers (HV) 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Intravenous 200 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US10702573 No 2020-07-07 2033-03-14 US US9526835 No 2016-12-27 2033-03-14 US US8722619 No 2014-05-13 2032-03-02 US US11197909 No 2021-12-14 2038-07-14 US US11654196 No 2012-03-02 2032-03-02 US US11712459 No 2017-03-15 2037-03-15 US US11819533 No 2018-07-11 2038-07-11 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Freely soluble FDA label - Predicted Properties
Property Value Source logP -1 Chemaxon pKa (Strongest Acidic) 2.86 Chemaxon pKa (Strongest Basic) 2.1 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 22 Chemaxon Hydrogen Donor Count 13 Chemaxon Polar Surface Area 383.87 Å2 Chemaxon Rotatable Bond Count 18 Chemaxon Refractivity 333.59 m3·mol-1 Chemaxon Polarizability 132.32 Å3 Chemaxon Number of Rings 7 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Aspergillus niger (strain CBS 513.88 / FGSC A1513)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- Rezafungin inhibits 1,3-beta-D-glucan synthase in many fungi, including Candida spp.
- General Function
- 1,3-beta-d-glucan synthase activity
- Specific Function
- Catalytic subunit of the 1,3-beta-glucan synthase. Synthesizes 1,3-beta-glucan, a major structural component of the cell wall. Involved in cell wall synthesis, maintenance and cell wall remodeling ...
- Gene Name
- fksA
- Uniprot ID
- A2QLK4
- Uniprot Name
- 1,3-beta-glucan synthase component FKS1
- Molecular Weight
- 216972.8 Da
References
- Kind
- Protein
- Organism
- Baker's yeast
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- Rezafungin inhibits 1,3-beta-D-glucan synthase in many fungi, including Candida spp.
- General Function
- Alternate catalytic subunit of the 1,3-beta-glucan synthase (GS). Synthesizes 1,3-beta-glucan, a major structural component of the yeast cell wall. Required for spore wall assembly. Negative regulation of activity by SMK1 is important for spore wall deposition. Activity is positively regulated by RHO1.
- Specific Function
- 1,3-beta-d-glucan synthase activity
- Gene Name
- GSC2
- Uniprot ID
- P40989
- Uniprot Name
- 1,3-beta-glucan synthase component GSC2
- Molecular Weight
- 216987.85 Da
References
Drug created at December 15, 2020 20:02 / Updated at April 04, 2023 03:32