Articles

Efficacy and safety of rezafungin and caspofungin in

candidaemia and invasive candidiasis: pooled data from two
prospective randomised controlled trials
George R Thompson III, Alex Soriano, Patrick M Honore, Matteo Bassetti, Oliver A Cornely, Marin Kollef, Bart Jan Kullberg, John Pullman,
Maya Hites, Jesús Fortún, Juan P Horcajada, Anastasia Kotanidou, Anita F Das, Taylor Sandison, Jalal A Aram, Jose A Vazquez, Peter G Pappas

Summary
Background Rezafungin, a new US Food and Drug Administration-approved, long-acting echinocandin to treat Lancet Infect Dis 2023
candidaemia and invasive candidiasis, was efficacious with a similar safety profile to caspofungin in clinical trials. We Published Online
conducted pooled analyses of the phase 2 STRIVE and phase 3 ReSTORE rezafungin trials. November 23, 2023
https://doi.org/10.1016/
S1473-3099(23)00551-0
Methods ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial conducted at 66 tertiary
See Online/Comment
care centres in 15 countries. STRIVE was a multicentre, double-blind, double-dummy, randomised phase 2 trial https://doi.org/10.1016/
conducted at 44 centres in 10 countries. Adults (≥18 years) with candidaemia or invasive candidiasis were treated with S1473-3099(23)00627-8
once-a-week intravenous rezafungin (400 mg and 200 mg) or once-a-day intravenous caspofungin (70 mg and 50 mg). Division of Infectious Diseases,
Efficacy was evaluated in a pooled modified intent-to-treat (mITT) population. Primary efficacy endpoint was day 30 Department of Internal
all-cause mortality (tested for non-inferiority with a pre-specified margin of 20%). Secondary efficacy endpoint was Medicine, and Department of
Medical Microbiology and
mycological response. Safety was also evaluated. The STRIVE and ReSTORE trials are registered with ClinicalTrials. Immunology, University of
gov, NCT02734862 and NCT03667690, and both studies are complete. California Davis Medical Center,
Sacramento, CA, USA
Findings ReSTORE was conducted from Oct 12, 2018, to Oct 11, 2021, and STRIVE from July 26, 2016, to April 18, 2019. (G R Thompson III MD); Hospital
Clínic de Barcelona, IDIBAPS,
The mITT population, pooling the data from the two trials, comprised 139 patients for rezafungin and 155 patients University of Barcelona,
for caspofungin. Day 30 all-cause mortality rates were comparable between groups (19% [26 of 139] for the rezafungin CIBERINFEC, Barcelona, Spain
group and 19% [30 of 155] for the caspofungin group) and the upper bound of the 95% CI for the weighted treatment (A Soriano PhD); Intensive Care
difference was below 10% ( −1·5% [95% CI −10·7 to 7·7]). Mycological eradication occurred by day 5 in 102 (73%) of Department, CHU UCL Namur
Godinne, UCL Louvain Medical
139 rezafungin patients and 100 (65%) of 155 caspofungin patients (weighted treatment difference 10·0% [95% CI School, Belgium
−0·3 to 20·4]). Safety profiles were similar across groups. (P M Honore PhD); Department
of Health Sciences, University
Interpretation Rezafungin was non-inferior to caspofungin for all-cause mortality, with a potential early treatment of Genoa, and Istituto di
Ricovero e Cura a Carattere,
benefit, possibly reflecting rezafungin’s front-loaded dosing regimen. These findings are of clinical importance in Ospedale Policlinico San
fighting active and aggressive infections and reducing the morbidity and mortality caused by candidaemia and Martino, Genoa, Italy
invasive candidiasis. (M Bassetti MD); Institute for
Translational Research, CECAD
Cluster of Excellence,
Funding Melinta Therapeutics and Cidara Therapeutics. University of Cologne, Cologne,
Germany (O A Cornely MD);
Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY Department I of Internal
Medicine, ECMM Excellence
4.0 license.
Center of Medical Mycology,
University Hospital Cologne,
Introduction are steadily increasing in prevalence.2 Resistance is a Cologne, Germany
Candidaemia and invasive candidiasis are important particular problem in the case of C glabrata, C parapsilosis, (O A Cornely); German Centre
for Infection Research, Bonn–
causes of morbidity and mortality in the health-care and the emerging species C auris, making them difficult
Cologne partner site, Cologne,
environment.1-5 They are also associated with a to treat.1,2 Echinocandins are first-line treatment in Germany (O A Cornely); Division
substantial economic burden, with per-patient direct Europe and the USA;7,8 however, the emergence of of Pulmonary and Critical Care
costs of US$48 487–157 574 in high-income countries in treatment-resistant Candida strains means that there is a Medicine, Washington
University, St Louis, MO, USA
2018.6 Guidelines recommend early treatment with the need to expand the armamentarium of available (M Kollef MD); Radboudumc
intent of mycological eradication,7 with earlier therapy antifungals.1,2 Center of Infectious Diseases
being associated with better overall outcomes (reduced Rezafungin is a new US Food and Drug Administration- and Radboud University
morbidity and mortality rates).8 approved echinocandin, which is struc­turally similar to the Medical Center, Nijmegen, The
Netherlands (B J Kullberg MD);
Despite considerable geographical variation in other three approved echinocandins with an established Clinical Research, Mercury
causative pathogen, the most common Candida species mechanism of action, but with stability and pharmaco­ Street Medical, Butte, MT, USA
implicated in candidaemia and invasive candidiasis in kinetics that allow once-weekly intra­venous administra­ (J Pullman MD); Hôpital
most clinical settings is Candida albicans, although non- tion and front-loaded dosing.9-12 Pharma­co­kinetic studies Universitaire de Bruxelles
Erasme, Brussels, Belgium
albicans species (Candida glabrata, Candida tropicalis, showed that rezafungin reaches a maximum plasma (M Hites PhD); Ramón y Cajal
Candida parapsilosis, Candida krusei, and Candida auris) concentration at approximately 1 h13 and that it has a University Hospital,

www.thelancet.com/infection Published online November 23, 2023 https://doi.org/10.1016/S1473-3099(23)00551-0 1

 Articles
CIBERINFEC, IRYCIS, Madrid,
Spain (J Fortún MD); Hospital
del Mar-IMIM, Universitat
Pompeu Fabra, Barcelona,
Spain (J P Horcajada MD); and
Centro de Investigación
Biomédica en Red de
Enfermedades Infecciosas,
Instituto de Salud Carlos III,
CIBERINFEC, Madrid, Spain
(J P Horcajada); University of
Athens Medical School,
National and Kapodistrian
University of Athens, Athens,
Greece (A Kotanidou MD);
Clinical Development, Cidara
Therapeutics, San Diego, CA,
USA (A F Das PhD,
T Sandison MD); Medical
Affairs, Melinta Therapeutics,
Parsippany, NJ, USA
(J A Aram MD); Department of
Medicine, Medical College of
Georgia, Augusta University
Medical Centre, Augusta, GA,
USA (J A Vazquez MD); Division
of Infectious Diseases,
Department of Internal
Medicine, University of
Alabama at Birmingham,
Birmingham, AL, USA
(P G Pappas MD)
Correspondence to:
Dr George R Thompson III,
Division of Infectious Diseases,
Department of Internal
Medicine, and Department of
Medical Microbiology and
Immunology, University of
California Davis Medical Center,
Sacramento, CA 95817, USA
grthompson@ucdavis.edu
2 www.thelancet.com/infection Published online November 23, 2023 https://doi.org/10.1016/S1473-3099(23)00551-0
Research in context
Evidence before this study
Candidaemia and invasive candidiasis are serious fungal
infections associated with high morbidity, mortality, and costs.
We searched PubMed for publications on echinocandins for the
treatment of candidaemia or invasive candidiasis, or both,
published between Jan 1, 2012, and May 17, 2023, with no
language restrictions, using the search terms ([echinocandin]
AND [candidaemia OR candidemia OR invasive candidiasis])
AND (treatment OR diagnosis OR management). Early
treatment initiation and mycological eradication are key to
reducing morbidity and mortality. The recommended first-line
treatment in Europe and the USA is echinocandins, but
treatment resistance presents an increasing challenge.
Rezafungin is an echinocandin with a similar structure to the
three other approved agents in the same class, but with
increased stability and a longer half-life that allow front-loaded,
once-weekly dosing. The phase 2 STRIVE and phase 3 ReSTORE
trials showed the clinical efficacy and safety of rezafungin versus
caspofungin in patients with candidaemia or invasive
candidiasis.
Added value of this study
The pooling of data from the STRIVE and ReSTORE clinical trials
provided a larger and more robust dataset for the analysis of
plasma half-life in healthy volunteers of more than 80 h
after the first dose, increasing to approximately 150 h after
the second or third dose.12 A population pharmacokinetic
study of rezafungin in patients with fungal infections
found that although relationships exist between rezafungin
pharmacokinetics and body surface area, infection status,
serum albumin, hepatic function, and sex, this inter-
individual variability is unlikely to be meaningful
clinically.14,15
Rezafungin has been evaluated in two similarly
designed, prospective, randomised clinical trials of
candidaemia and invasive candidiasis: the phase 2
STRIVE trial (NCT02734862) and the phase 3 ReSTORE
trial (NCT03667690). In STRIVE, rezafungin was found
to be efficacious with a similar safety and tolerability
profile to that of caspofungin.16 In ReSTORE, once-
weekly rezafungin (using a dosing regimen of 400 mg
and 200 mg) was non-inferior for 30-day all-cause
mortality to once-daily caspofungin (70 mg and 50 mg),
with a similar safety profile.17 Data from both trials
suggested potential early treatment benefits versus
caspofungin,16,17 probably due to the high plasma
concentrations of rezafungin achieved early in therapy as
a result of its front-loaded dosing.16,17
The similar designs of these two clinical trials allow
data to be pooled to provide a robust dataset for
further analysis. Here we report findings from pooled
efficacy and safety analyses of the STRIVE and ReSTORE
trials.
efficacy and safety outcomes for rezafungin and caspofungin.
Differences in trial design and outcome definitions between the
two trials were addressed by the statistical methodologies used
to conduct the pooled analyses. The analyses supported the
non-inferiority of rezafungin versus caspofungin for all-cause
mortality and provided additional evidence for potential early
treatment benefits of rezafungin, as well as confirming the
similarity of its safety profile to that of caspofungin.
Mycological eradication rates and negative blood culture results
suggest that rezafungin treatment could achieve rapid infection
clearance.
Implications of all the available evidence
The results of the pooled analysis underscore the efficacy and
safety findings reported in the individual clinical trials. The early
treatment benefits (rapid eradication) seen in the rezafungin
group support the importance of prompt antifungal therapy to
reduce the morbidity and mortality caused by candidaemia and
invasive candidiasis. The high rate of early mycological
eradication with front-loaded dosing of rezafungin is an
important clinical consideration in fighting active and
aggressive infections.
Methods
Study design and participants
Full methodological details of the STRIVE and ReSTORE
trials, including ethical approvals, have been described
previously. In brief, both trials were international,
multicentre, double-blind, randomised controlled trials
and were conducted in adults with candidaemia or
invasive candidiasis, or both. Eligible patients had
systemic signs of candidaemia or invasive candidiasis, or
both, plus mycological evidence obtained from blood or a
normally sterile sampling site within 96 h before
randomisation.16,17
This analysis pooled data from groups in the STRIVE
and ReSTORE trials that received similar dosing
regimens. In the case of rezafungin, this comprised
patients who received once-weekly intravenous
rezafungin via a front-loaded regimen of 400 mg on
day 1, then 200 mg on day 8 (plus optional 200-mg doses
on day 15 and, in ReSTORE and in patients with invasive
candidiasis in STRIVE, day 22). For caspofungin, data
were pooled from groups that received once-daily
intravenous caspofungin at 70 mg on day 1, followed by
50 mg per day for at least 3 and up to 21 days (28 days in
ReSTORE and in patients with invasive candidiasis with
or without candidaemia in STRIVE). Stable participants
who met relevant criteria could step down to oral therapy
after 3 or more days of intravenous therapy. For
rezafungin groups, this was to a placebo. For caspofungin
groups, stepdown was to fluconazole.

Outcomes
The primary pooled efficacy endpoint was all-cause
mortality at day 30. This endpoint comprised patients
who died on or before day 30 or those with unknown
survival status; patients who were alive at day 28 or day 29
but had an unknown survival status at day 30 were
considered to be alive for the purposes of this calculation.
Secondary pooled efficacy endpoints included the
proportion of patients with mycological eradication at
day 5 and day 14. Mycological eradication was defined,
for patients with a positive blood culture at baseline, as a
negative blood culture on or before the day of assessment
(ie, day 5 or day 14) with no subsequent positive culture.
For patients with a positive culture at baseline from a
normally sterile site other than blood, mycological
eradication was either documented (a negative culture
from the same normally sterile site on or prior to the day
of assessment [ie, day 5 or day 14]) or presumed
(assessment of clinical and radiological cure [ for those
with evidence of disease on imaging at baseline] if a
specimen from the infected site was not available). The
mycological eradication definition also required patients
to be alive, have had no change in antifungal therapy for
the treatment of candidaemia or invasive candidiasis, or
both, nor to have been lost to follow-up on the day of
assessment.
Subgroup analyses were conducted for the primary
endpoint and for mycological response, comprising
analysis by age, race, gender, geographical region, BMI,
absolute neutrophil count, renal impairment, Acute
Physiology and Chronic Health Evaluation (APACHE) II
score, diagnosis, and timing of positive culture. In the
renal impairment subanalysis, normal function to mild
impairment was classed as creatinine clearance of at
least 60 mL/min; clearance of less than 60 mL/min was
classed as moderate to severe impairment.
Exploratory pooled efficacy endpoints included:
mycological eradication in a subset of patients with a
positive blood culture proximal to randomisation (ie,
taken from blood sampled within 12 h before or 72 h after
randomisation or, if obtained from another normally
sterile site, within 48 h before or 72 h after randomisation);
the proportion of patients with a negative blood culture
at 24 h and 48 h (of those with a positive culture at
baseline); and time to first negative blood culture in the
subsets of patients with a positive blood culture at
baseline and in those with a positive blood culture
proximal to randomisation (as defined here). Time to
negative culture was calculated as the time from first
dose of study drug to the time of the first negative culture
without subsequent positive cultures. Pooled global
response at day 14 was also analysed as an exploratory,
post-hoc endpoint. For STRIVE, this was determined
based on investigator assessment of clinical response
and mycological eradication. For ReSTORE, this was
based on clinical response, mycological eradication, and
radiological response (for patients with evidence of
www.thelancet.com/infection Published online November 23, 2023 https://doi.org/10.1016/S1473-3099(23)00551-0
Articles
disease on imaging at baseline), as determined by a
blinded, independent data review committee. In an
additional exploratory, post-hoc analysis, rates of
mycological eradication and relapse or reinfection
(documented by subsequent positive cultures) were
documented at follow-up (day 45–52 for patients with
candidaemia or day 52–59 for those with invasive
candidiasis in STRIVE; and day 52–59 for all patients in
ReSTORE). Other efficacy endpoints reported in the two
trials could not be pooled owing to the use of different
definitions and measures of outcomes.
Pooled safety endpoints included treatment-emergent
adverse events, study drug-related treatment-emergent
adverse events, treatment-emergent adverse events that
led to study drug discontinuation, serious adverse events,
study drug-related serious adverse events, and adverse
events of special interest. Adverse events were coded
using Medical Dictionary for Regulatory Activities
(MedDRA; version 23.0). In STRIVE, adverse events
were graded as mild, moderate, or severe. In ReSTORE,
severity grading was per the National Cancer Institute
Common Terminology Criteria for Adverse Events
(NCI-CTCAE; version 5.0). In this pooled analysis,
severity was defined as mild (encompassing mild or
grade 1), moderate (moderate or grade 2), or severe
(severe or grade ≥3). Pooled data were also analysed for
clinical laboratory evaluations (haematology and
chemistry) and vital signs (temperature, heart rate, blood
pressure, and respiratory rate).
Statistical analysis
Efficacy endpoints were analysed in the modified intent-
to-treat (mITT) population, which included all patients
with a documented Candida infection within 96 h before
randomisation who received at least one dose of study
drug. A post-hoc analysis of all-cause mortality at day 30
was conducted in a clinically evaluable population, which
is similar to a per-protocol population. The clinically
evaluable population included all patients in the mITT
population who met inclusion criteria, did not meet
exclusion criteria that could affect efficacy, received the
correct study drug, had not received a non-study
antifungal agent (except to treat the underlying
candidaemia or invasive candidiasis from the first dose
of study drug through day 30), and had a known survival
status.
For some secondary and exploratory efficacy analyses,
subsets of the mITT population were analysed, as
described. Safety endpoints were assessed in the safety
population, defined as all participants who received study
drug.
Non-inferiority for the pooled primary efficacy
outcome, all-cause mortality at day 30, was evaluated in
the mITT population using a two-sided 95% CI for the
weighted (by study and study part [ for the two-part
STRIVE study]) treatment difference, calculated using
the Miettinen and Nurminen stratified method. Inverse
3
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Secondary efficacy outcomes and subgroup analyses

Rezafungin (n=139) Caspofungin (n=155)
were also analysed by calculating weighted treatment
Age, years 60 (49–71) 62 (52–71) difference and corresponding 95% CIs, using the
Gender stratified Miettinen and Nurminen methodology.
Male 90 (65%) 90 (58%) However, the CIs are provided for exploratory and not
Female 49 (35%) 65 (42%) confirmatory purposes.
Race For the exploratory outcome of time to first negative
White 95 (68%) 106 (68%) culture, Kaplan–Meier methods were used for analysis. A
Asian 24 (17%) 34 (22%) p value was determined using a stratified log-rank test.
Black or African American 11 (8%) 8 (5%) Patients were censored if they received an alternative
American Indian or Alaska Native 1 (<1%) 1 (<1%) antifungal (ie, other than study drug), died, or were lost
Native Hawaiian or other Pacific Islander 0 0 to follow-up before having a negative blood culture.
Other 3 (2%) 2 (1%) Safety endpoints were summarised using descriptive
Not reported 5 (4%) 4 (3%) statistics. Ad-hoc p-values were calculated using Fisher’s
Ethnicity exact test and are provided for exploratory and not
Not-Hispanic or not-Latino 121 (87%) 141 (91%) confirmatory purposes.
Hispanic or Latino 13 (9%) 10 (7%)
Not reported 5 (4%) 4 (3%) Role of the funding source
BMI, kg/m² 24·10 (20·76–28·69) 24·34 (21·12–27·65) Employees of the funding sources were involved in the
Final diagnosis* study design; the collection, analysis, and interpretation
Candidaemia only 100 (72%) 115 (74%) of data; and in the writing of the report.
Invasive candidiasis 39 (28%) 40 (26%)
Positive Candida culture proximal to randomisation† 53 (38%) 71 (46%) Results
Catheter placement‡ Patient disposition is reported in appendix 1 (pp 2–3).
Yes 91/115 (79%) 107/130 (82%) The mITT population comprised 294 patients (139 in the
Removed within 48 h of diagnosis 24/115 (21%) 33/130 (25%) rezafungin group and 155 in the caspofungin group)
Modified APACHE II score
across the STRIVE and ReSTORE trials. In this
≥20 21/137 (15%) 26/152 (17%)
population, 44 (32%) patients in the rezafungin group
<20 116/137 (84%) 126/152 (81%)
and 50 (32%) in the caspofungin group discontinued the
study early. Of these, 24 (17%) of 139 cases in rezafungin
Absolute neutrophil count at randomisation
group and 30 (19%) of 155 cases in caspofungin group
<500 cells per µL 7/135 (5%) 5/151 (3%)
were due to patient death.
≥500 cells per µL 128/135 (92%) 146/151 (94%)
Groups were generally well balanced with respect to
Renal impairment category based on creatinine clearance, n (%)
demographics and baseline characteristics (table 1). Most
≥60 mL/min (normal to mild) 75 (54%) 83 (54%)
participants (116 [84%] of 139 for rezafungin and
<60 mL/min (moderate to severe) 54 (39%) 59 (38%)
126 [81%] of 155 for caspofungin) had a modified
Child-Pugh score category
APACHE II score lower than 20 and approximately half
<7 0 1 (<1%)
of patients in both groups had normal renal function to
≥7 3 (2%) 9 (6%)
mild impairment (75 [54%] of 139 for rezafungin and
No history of liver disease or not calculated 136 (98%) 145 (94%)
83 [54%] of 155 for caspofungin). Similar proportions of
Data are n (%), median (IQR). APACHE=Acute Physiology and Chronic Health Evaluation. mITT=modified intent-to- patients had intravascular catheter placement at baseline
treat. Where the number of evaluable patients in each group did not correspond to the total number of patients, (91 [79%] of 115 for rezafungin and 107 [82%] of 130 for
numbers are specified. *For ReSTORE, determined based on the radiological or tissue culture assessment, or both,
caspofungin). Most participants had an absolute
through day 14; for STRIVE, the same as the baseline diagnosis. †Defined as a culture from blood drawn within 12 h
before randomisation or within 72 h after randomisation, or a culture from another normally sterile site obtained neutrophil count of at least 500 cells per µL at
within 48 h prior to randomisation or within 72 h after randomisation. ‡For ReSTORE, the population is mITT with a randomisation (128 [92%] of 139 for rezafungin and
positive blood culture at baseline. 146 [94%] of 155 for caspofungin). Candida spp were
Table 1: Demographics and baseline characteristics (mITT population) similarly distributed across the two treatment groups
(appendix 1 p 4). Overall, of 294 patients, 127 (43%) had
infections caused by C albicans, 73 (25%) by C glabrata,
See Online for appendix 1 variance of the effect size was used for the stratum 49 (17%) by C tropicalis, and 41 (14%) by C parapsilosis.
weights. To show non-inferiority of rezafungin to Most patients (>70%) in both treatment groups had
caspofungin, the upper limit of the 95% CI was required candidaemia only. The distribution of infection sites
to be below 20% (ie, a 20% non-inferiority margin). A among patients with invasive candidiasis was comparable
sensitivity analysis of the primary efficacy outcome, between the two groups (appendix 1 p 5). The most
excluding participants with an unknown survival status, common infection site was the intraabdominal or
and an analysis in the clinically evaluable population peritoneal space, as observed in 26 (67%) of 39 patients
were conducted using the same methodology. with invasive candidiasis in rezafungin and 28 (70%) of

4 www.thelancet.com/infection Published online November 23, 2023 https://doi.org/10.1016/S1473-3099(23)00551-0

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40 patients with invasive candidiasis in caspofungin

Rezafungin Caspofungin Treatment difference
groups. (n=139) (n=155) (95% CI)
In the mITT population, median duration of study
Primary pooled efficacy endpoint: day 30 all-cause mortality
drug exposure for patients who received intravenous
Deceased or unknown survival status 26 (19%) 30 (19%) ∙∙
therapy only was 14·0 days (IQR 8·0–14·0) in the
Known deceased 21 (15%) 25 (16%) ∙∙
rezafungin group and 14·0 days (8·0–15·0) in the
Unknown survival status 5 (4%) 5 (3%) ∙∙
caspofungin group. Following intravenous therapy,
Alive 113 (81%) 125 (81%) ∙∙
39 (28%) of 139 patients in the rezafungin group and
Death rate* ∙∙ ∙∙ −1·5% (−10·7 to 7·7)
56 (36%) of 155 patients in the caspofungin group
Secondary efficacy endpoints
switched to oral stepdown therapy. Switching most
Day 5 mycological response
commonly occurred on days 4–6, as noted in 22 (56%) of
39 patients treated with rezafungin and 26 (46%) of Eradication 102 (73%) 100 (65%) ∙∙

56 patients treated with caspofungin. Median study drug Failure or indeterminate 37 (27%) 55 (35%) ∙∙

exposure for intravenous and oral therapy combined Eradication rate* ∙∙ ∙∙ 10·0% (−0·3 to 20·4)
was similar for both treatment groups: 14·0 days Day 14 mycological response
(IQR 10·0–14·0) for rezafungin and 14·0 days (13·0–15·0) Eradication 100 (72%) 106 (68%) ∙∙
for caspofungin treatment. Failure or indeterminate 39 (28%) 49 (32%) ∙∙
Rates of all-cause mortality at day 30 were 19% Eradication rate* ∙∙ ∙∙ 4·3% (−6·2 to 14·7)
(26 of 139) for the rezafungin group and 19% (30 of 155) Exploratory efficacy endpoints
for the caspofungin group (weighted treatment difference Patients with negative blood culture†‡
−1·5% [95% CI −10·7 to 7·7]; table 2). Rezafungin At 24 h 63/105 (60%) 57/116 (49%) ∙∙
therefore met the prespecified criteria for non-inferiority At 48 h 80/103 (78%) 73/115 (64%) ∙∙
to caspofungin, as the upper limit of the 95% CI for the Day 14 global response§
treatment difference was within a 10% non-inferiority Cure 90 (65%) 97 (63%) ∙∙
margin and thus met the prespecified non-inferiority Failure 36 (26%) 48 (31%) ∙∙
margin of 20%. A small proportion of patients (five [4%] Indeterminate 13 (9%) 10 (6%) ∙∙
of 139 in the rezafungin group and five [3%] of 155 in the Cure rate* ∙∙ ∙∙ 2·3% (−8·2 to 13·9)
caspofungin group) had an unknown survival status at
mITT=modified intent-to-treat. *95% CI calculated using stratified (by study and, where applicable, study part)
day 30. A sensitivity analysis in which these patients were Miettinen and Nurminen methodology. †Denominator is patients in the mITT population with a positive blood culture
excluded produced similar results to the primary at baseline. ‡Patients who received an alternative antifungal, died, or were lost to follow-up prior to 24 h and 48 h
analysis (weighted treatment difference −2·0% [95% CI were censored and excluded from the denominator. §In STRIVE, global response was determined based on the
investigator’s assessment of clinical response and mycological response; in ReSTORE, global response was determined
−10·8 to 6·8]), as did an analysis in the clinically evaluable
based on clinical response, mycological response, and radiological response, and confirmed by an independent data
population (−3·0% [−11·5 to 6·4]; appendix 1 p 6). review committee.
Subgroup analyses for all-cause mortality at day 30 are
Table 2: Summary of efficacy data (mITT population, unless otherwise stated)
summarised in figure 1. In patients younger than
65 years, the treatment difference between rezafungin
(18 [22%] of 82) and caspofungin (ten [11%] of 92) was Results of the secondary outcome of mycological
10·9% (95% CI −1·0 to 22·8), favouring caspofungin. In eradication at day 5 and day 14 are summarised in table 2.
those aged 65 years or older, the treatment difference At day 5, the proportion of patients in the mITT
was −17·6% (−32·5 to −2·8), favouring rezafungin population with mycological eradication was 73%
(eight [14%] of 57) over caspofungin (20 [32%] of 63). In (102 of 139) in the rezafungin group and 65% (100 of 155)
the subgroup of patients with normal renal function in the caspofungin groups (weighted treatment
to mild renal impairment (creatinine clearance difference 10·0% [95% CI −0·3 to 20·4]). In subgroup
≥60 mL/min), the treatment difference was 11·3% analyses, a larger treatment difference was noted in
(95% CI −1·1 to 23·7), favouring caspofungin. In those patients with candidaemia only (weighted treatment
with moderate to severe renal impairment (creatinine difference 12·9% [95% CI 1·5 to 24·3]), and in those with
clearance <60 mL/min), the treatment difference was a positive blood culture proximal to randomisation (from
−18·2% (−33·1 to −3·2), favouring rezafungin. No a blood sample obtained within 12 h before or 72 h after
apparent treatment difference between rezafungin and randomisation or a sample from a normally sterile site
caspofungin groups was observed for the subgroup of obtained within 48 h before or 72 h after randomisation),
patients with candidaemia only as diagnosis (−0·9% weighted treatment difference 19·2% [95% CI
[−12·2 to 10·4]). There was also no apparent treatment 3·0 to 35·5]). Mycological eradication rates were similar
difference between rezafungin and caspofungin groups at day 14 and comparable across treatment groups. At
for all-cause mortality at day 30 according to Candida day 14, rates in the mITT population were 72% (100 of 139)
species (appendix 1 p 7). Mycological response at day 5 and 68% (106 of 155) in the rezafungin and caspofungin
and day 14 by Candida species is shown in the appendix 1 groups, respectively (weighted treatment difference
(pp 8–9). 4·3% [95% CI −6·2 to 14·7]). A larger treatment

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Participants who died or with unknown survival status Difference (95% CI)

Rezafungin, n/N (%) Caspofungin, n/N (%)

Overall 26/139 (18·7) 30/155 (19·4) –1·5 (–10·7 to 7·7)

Age
18 to <65 years 18/82 (22·0) 10/92 (10·9) 10·9 (–1·0 to 22·8)
≥65 years 8/57 (14·0) 20/63 (31·7) –17·6 (–32·5 to –2·8)
65 to <75 years 5/32 (15·6) 8/32 (25·0) –8·6 (–29·3 to 12·0)
≥75 years 3/25 (12·0) 12/31 (38·7) –22·4 (–43·6 to –1·1)
Race
White 14/95 (14·7) 17/106 (16·0) –2·8 (–13·3 to 7·6)
Non-White 11/39 (28·2) 13/45 (28·9) –0·4 (–19·3 to 18·6)
Gender
Male 20/90 (22·2) 17/90 (18·9) 1·1 (–10·8 to 13·1)
Female 6/49 (12·2) 13/65 (20·0) –6·7 (–21·4 to 7·9)
Geographic region
North and South America 6/43 (14·0) 4/46 (8·7) 4·1 (–11·5 to 19·8)
Europe, Israel, and Turkey 10/67 (14·9) 15/76 (19·7) –6·6 (–19·2 to 6·1)
Asia-Pacific (excluding China and Taiwan) 8/21 (38·1) 10/27 (37·0) 1·4 (–25·7 to 28·4)
China and Taiwan 2/8 (25·0) 1/6 (16·7) 4·9 (–39·6 to 49·5)
BMI
<25 kg/m2 (underweight or normal) 12/75 (16·0) 16/75 (21·3) –4·1 (–16·9 to 8·6)
25–30 kg/m2 (overweight) 6/28 (21·4) 8/48 (16·7) 7·6 (–11·3 to 26·4)
>30 kg/m2 (obese) 7/30 (23·3) 3/21 (14·3) 3·9 (–19·5 to 27·4)
ANC count
ANC <500 cells/µL 4/7 (57·1) 1/5 (20·0) 26·8 (–21·3 to 74·8)
ANC ≥500 cells/µL 22/128 (17·2) 28/146 (19·2) –2·5 (–11·9 to 7·0)
Renal impairment
≥60 mL/min (normal or mild) 17/75 (22·7) 9/83 (10·8) 11·3 (–1·1 to 23·7)
<60 mL/min (moderate or severe) 7/54 (13·0) 18/59 (30·5) –18·2 (–33·1 to –3·2)
APACHE II
APACHE <10 5/51 (9·8) 6/53 (11·3) –2·2 (–15·8 to 11·5)
APACHE 10–19 14/65 (21·5) 14/73 (19·2) 0·0 (–13·6 to 13·6)
APACHE <20 19/116 (16·4) 20/126 (15·9) 0·1 (–9·6 to 9·9)
APACHE ≥20 5/21 (23·8) 10/26 (38·5) –11·6 (–36·6 to 13·5)
Final diagnosis*
Candidaemia only 22/100 (22·0) 26/115 (22·6) –0·9 (–12·2 to 10·4)
Invasive candidiasis 4/39 (10·3) 4/40 (10·0) 0·6 (–15·6 to 16·8)
Positive culture within window
Yes 11/53 (20·8) 15/71 (21·1) –0·3 (–15·5 to 14·8)
No 15/86 (17·4) 15/84 (17·9) –1·0 (–13·0 to 11·1)

–100 –60 –20 0 20 60 100

Favours rezafungin Favours caspofungin

Figure 1: Subgroup analyses of 30-day all-cause mortality rate (primary efficacy endpoint; mITT population)
ANC=absolute neutrophil count. APACHE=Acute Physiology and Chronic Health Evaluation. mITT=modified intent-to-treat. Two-sided 95% CI were calculated using
the Miettinen and Nurminen stratified (by study and part) method. *For ReSTORE, determined based on the radiological or tissue culture assessment, or both,
through day 14; for STRIVE, the same as the baseline diagnosis.

difference was reported in the subgroup of patients with
a positive blood culture proximal to randomisation
(treatment difference 13·4% [95% CI −2·8 to 29·5]).
Rates of mycological eradication and relapse or rein­
fection at follow-up were comparable across treatment
groups (appendix 1 p 10).
At 24 h, 63 (60%) of 105 patients in the rezafungin
group and 57 (49%) of 116 in the caspofungin group had
a negative blood culture (table 2). At 48 h, 80 (78%) of
103 patients in the rezafungin group and 73 (64%) of
115 in the caspofungin group had a negative blood
culture. An exploratory Kaplan–Meier analysis of time to
first negative blood culture suggested that rezafungin
may be associated with a shorter time to negative blood
culture than caspofungin (figure 2A). There was a more
pronounced difference in time to first negative blood
culture in those with a positive blood culture proximal to
randomisation (figure 2B).
Global cure rate at day 14 was similar between
treatment groups: 65% (90 of 139) for the rezafungin

6 www.thelancet.com/infection Published online November 23, 2023 https://doi.org/10.1016/S1473-3099(23)00551-0

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group and 63% (97 of 155) for the caspofungin group

A
(weighted treatment difference 2·3% [95% CI 1·0
−8·2 to 13·9]; table 2).

Probability of negative blood culture

0·9
The safety data are summarised in table 3. Treatment- 0·8
emergent adverse events occurred in 138 (91%) of 0·7
151 patients in the rezafungin group and 138 (83%) of 0·6
0·5
166 in the caspofungin group. The most common
0·4
treatment-emergent adverse events, occurring in at least 0·3
10% of either treatment group, were hypokalaemia, Rezafungin
0·2 Caspofungin
pyrexia, and diarrhoea. Those occurring in at least 5% of 0·1 p=0·0051 (log rank)
participants in either group are detailed in table 3. 0
0 24 48 72 96 120 144 168 192
Study drug-related treatment-emergent adverse events
Number at risk
occurred in 22 (15%) of 151 participants in the rezafungin (number censored)
group and 18 (11%) of 166 participants in the caspofungin Rezafungin 109 (0) 42 (2) 23 (4) 13 (6) 10 (6) 9 (6) 8 (6) 7 (6) 7 (6)
Caspofungin 122 (0) 59 (3) 42 (4) 30 (7) 27 (8) 23 (9) 19 (10) 19 (10) 16 (12)
group. Study drug-related serious adverse events
occurred in three (2%) of 151 participants in the B
rezafungin group and five (3%) of 166 participants in the Probability of negative blood culture
1·0
caspofungin group. Post-baseline renal toxicity (defined 0·9
as a doubling of serum creatinine relative to baseline or 0·8
an increase of ≥1 mg/dL in serum creatinine if baseline 0·7
0·6
serum creatinine was above the upper limit of the
0·5
normal range) occurred in 14 (10%) of 145 participants in 0·4
the rezafungin group and 28 (17%) of 162 in the 0·3
caspofungin group (among those with available data). 0·2
Potentially drug-induced liver injury adverse events were 0·1 p=0·015 (log rank)
reported in 21 (14%) of 151 patients in the rezafungin 0
0 24 48 72 96 120 144 168 192
group and 29 (18%) of 166 in the caspofungin group. Time since first dose (hours)
Number at risk
Increases of two or more grades in clinical laboratory (number censored)
values occurred at similar rates across both groups Rezafungin 42 (0) 20 (1) 18 (1) 12 (3) 9 (3) 8 (3) 7 (3) 6 (3) 6 (3)
(appendix 1 p 11). Changes in vital signs deemed Caspofungin 53 (0) 39 (2) 30 (3) 20 (6) 18 (7) 15 (8) 13 (9) 13 (9) 10 (11)

potentially clinically significant also generally occurred
at similar rates across both groups (appendix 1 p 12).
One patient with candidaemia only (from the ReSTORE
trial) required continuous veno-venous haemofiltration
and sub­sequently died.
Discussion
This pooled analysis examined efficacy and safety data
Figure 2: Time to first negative blood culture in (A) patients with a positive blood culture at screening and
(B) those with a positive blood culture proximal to randomisation (mITT population, patients with a
positive culture at screening)
mITT=modified intent-to-treat. The timing of a positive blood culture was considered to be proximal to
randomisation if it was taken from blood sampled within 12 h before or 72 h after randomisation. Crosses indicate
censored patients; patients were censored if they received an alternative antifungal (ie, other than study drug) for
the treatment of the candidaemia, died, or were lost to follow-up before having the negative blood culture.
The p value cannot be interpreted as hypothesis-testing because this was an exploratory outcome within a
subgroup of patients.

from two similarly designed phase 2 and phase 3 trials of

rezafungin versus caspofungin, conducted in patients
with candidaemia and invasive candidiasis. Once-weekly
rezafungin was found to be non-inferior to once-daily
caspofungin with respect to the primary efficacy
endpoint, all-cause mortality at day 30.
The secondary and exploratory efficacy findings
suggest that rezafungin can have an early treatment
benefit, including higher mycological eradication rates at
earlier timepoints and potentially a faster time to negative
culture, particularly in patients with a positive blood
culture proximal to randomisation. Although not yet
shown, earlier and higher rates of mycological eradication
have the potential to contribute to a decrease in the
selection of resistant strains. Safety profiles were similar
for rezafungin and caspofungin, including with respect
to renal and hepatic findings.
Echinocandins are recommended as first-line treat­
ment in candidaemia and invasive candidiasis.7,8 They are
efficacious18,19 and associated with high rates of treatment
success, including improved survival.20,21 However, the
effectiveness of first-generation echino­ candins can be
impeded by underdosing: dosing of first-generation
echinocandins might be inadequate in the context of
increased minimum inhibitory concentrations coupled
with the pharmacokinetic variability observed in critically
ill patients, those with moderate to severe hepatic
impairment, and patients with obesity.22
The echinocandin rezafungin is characterised by its
enhanced stability and improved pharmacokinetics,
which enable once-weekly dosing and front-loaded
exposure.9-12 The current pooled analysis supports the
early treatment benefits of high front-loaded rezafungin
exposure, as shown by the mycological eradication rates
seen at day 5 and clearance of blood cultures at 24 h and
48 h after the first dose of rezafungin. Dosing and timing
of antifungal administration are key factors in the

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more pronounced among patients who had a positive

Rezafungin Caspofungin p value*
(n=151) (n=166) culture at the time of randomisation or shortly thereafter.
These observations are valuable clinical considerations
≥1 adverse event 139 (92%) 138 (83%) 0·018
for the use of once-weekly rezafungin against active
≥1 treatment-emergent adverse event 138 (91%) 138 (83%) 0·0304
infections versus once-daily caspofungin treatment.
≥1 study drug-related treatment-emergent adverse event 22 (15%) 18 (11%) 0·3975
Echinocandins act via concentration-dependent
≥1 severe or grade ≥3 treatment-emergent adverse event 74 (49%) 85 (51%) 0·74
killing;23 therefore, according to pharmacokinetic and
≥1 adverse event of special interest 10 (7%) 5 (3%) 0·19
pharmacodynamic principles, they are most effective
≥1 serious adverse event 83 (55%) 81 (49%) 0·31
when higher doses are administered infrequently.12,24-26
≥1 study drug-related serious adverse event 3 (2%) 5 (3%) 0·73
The early eradication seen with rezafungin versus
≥1 serious adverse event leading to death 35 (23%) 40 (24%) 0·8951
caspofungin could therefore be attributed to the higher
≥1 study drug-related serious adverse event leading to death 0 0 NA front-loaded exposure of rezafungin versus caspofungin
≥1 treatment-emergent adverse event leading to interruption of 3 (2%) 4 (2%) 1·000 (400 mg vs 70 mg). The early mycological eradication
study drug
seen with rezafungin might help to avoid the
≥1 treatment-emergent adverse event leading to 14 (9%) 15 (9%) 1·000
discontinuation of study drug development of resistance, although supportive evidence
≥1 treatment-emergent adverse event leading to study 24 (16%) 32 (19%) 0·46 is currently absent. The development of resistance can
discontinuation also be expected to be reduced as a result of the high
Most commonly occurring treatment-emergent adverse events plasma drug concentrations achieved early in therapy
(≥5% of either pooled treatment group) with front-loaded, once-weekly dosing, given that the
Infections and infestations frequency of spontaneous mutants inducing reduced
Pneumonia 12 (8%) 7 (4%) 0·24 susceptibility to rezafungin has been found to be similar
Septic shock 11 (7%) 12 (7%) 1·000 to that observed for anidulafungin and caspofungin.27
Sepsis 10 (7%) 8 (5%) 0·63 In contrast to rezafungin, other echinocandins
Urinary tract infection 5 (3%) 9 (5%) 0·42 (anidulafungin, caspofungin, and micafungin) require
Gastrointestinal disorders daily administration.28 The once-weekly dosing regimen
Diarrhoea 17 (11%) 17 (10%) 0·86 of rezafungin has potential clinical benefits, such as
Vomiting 14 (9%) 7 (4%) 0·11 fewer health-care touchpoints, fewer infusions and
Nausea 13 (9%) 8 (5%) 0·18 indwelling catheters,17 and also has the potential to
Abdominal pain 11 (7%) 9 (5%) 0·64 improve adherence, particularly for patients requiring a
Constipation 8 (5%) 8 (5%) 1·000 long course of treatment. The safety and tolerability of
Metabolism and nutrition disorders long-term rezafungin in a patient with multidrug-
Hypokalaemia 22 (15%) 17 (10%) 0·3045 resistant C glabrata infection has been shown in a 2021
Hypomagnesaemia 12 (8%) 5 (3%) 0·078 case report.29
Hypophosphataemia 8 (5%) 5 (3%) 0·3983 Analyses of all-cause mortality at day 30 among
Hyperkalaemia 3 (2%) 9 (5%) 0·14 subgroups of patients favoured caspofungin in patients
Other disorders
younger than 65 years but favoured rezafungin in those
Pyrexia 18 (12%) 11 (7%) 0·12
aged 65 years or older; and favoured caspofungin in
Pleural effusion 3 (2%) 10 (6%) 0·0904
patients with normal renal function to mild renal
Anaemia 15 (10%) 13 (8%) 0·56
impairment but rezafungin in patients with moderate to
severe renal impairment. Studies have reported that
Hypotension 7 (5%) 10 (6%) 0·63
relationships between markers of renal or hepatic
Acute kidney injury 6 (4%) 11 (7%) 0·33
impairment and rezafungin pharmacokinetic measures
NA=not applicable. Percentages were calculated using the total number of patients in each treatment group as the are unlikely to be clinically meaningful;14,15 nonetheless,
denominator. Adverse event of special interest consisted of intravenous infusion intolerability, phototoxicity, and the treatment differences between caspofungin and
neurological adverse events (ataxia, tremors, and neuropathy [ataxia, axonal neuropathy, hypoaesthesia, paraesthesia,
peripheral motor neuropathy, peripheral neuropathy, peripheral sensory neuropathies, peripheral sensorimotor rezafungin in all-cause mortality rates from the
neuropathy, polyneuropathy, or toxic neuropathy]). *p values from Fisher’s exact test. exploratory subgroup analyses in our analysis could
warrant further investigation.
Table 3: Safety summary and most commonly occurring treatment-emergent adverse events (safety
population) The similarity between the designs of the STRIVE and
ReSTORE trials allowed pooling of data to generate a
robust dataset. The analysis included patients with
successful treatment of candidaemia and invasive C albicans, C glabrata, C tropicalis, and C parapsilosis,
candidiasis.2 Multiple studies have shown that delay in making findings likely to be generalisable across Candida
antifungal therapy is one of the major contributors to species. The analysis is, however, subject to limitations:
increased morbidity and mortality;8 in this pooled there were differences in trial design, including with
analysis, differences between rezafungin and caspofungin respect to definitions and measures of outcomes.
in the percentage of patients with negative blood culture Specifically, the phase 2 STRIVE trial was conducted in
at 24 h and 48 h and time to negative blood culture were two parts, with three and two treatment groups,

8 www.thelancet.com/infection Published online November 23, 2023 https://doi.org/10.1016/S1473-3099(23)00551-0


respectively, whereas the phase 3 ReSTORE trial
comprised two treatment groups. In addition, the
ReSTORE trial included patients from Europe, the Asia-
Pacific region, the USA, and South America, whereas the
STRIVE trial only included patients from Europe and the
USA. Furthermore, global response at day 14, analysed as
an exploratory, post-hoc endpoint, was determined based
on investigator assessment of clinical response and
mycological eradication in STRIVE, but was based on
clinical response, mycological eradication, and radio­
logical response, as determined by an independent,
blinded data review committee, in ReSTORE. Adverse
events were also graded differently: as mild, moderate, or
severe in STRIVE but as grade 1, grade 2, or grade 3 or
greater in ReSTORE.16,17 These limitations were addressed
in the statistical analysis methodology, which controlled
for study and study part and, where appropriate, included
only such data that could be analysed in a consistent
manner.
In conclusion, this pooled analysis further supports the
efficacy and safety of rezafungin in treating candidaemia
and invasive candidiasis. Rezafungin was non-inferior to
caspofungin for 30-day all-cause mortality, with a potential
early treatment benefit and similar safety profile. This
may reflect rezafungin’s front-loaded dosing regimen.
The availability of rezafungin as a new antifungal is a
valuable addition to candidaemia and invasive candidiasis
treatments and may help to address the growing challenge
of treatment-resistant Candida strains and species.
Contributors
AFD, BJK, OAC, PGP, GRT, and TS designed the study. AFD and TS
collected the data. AFD and GRT directly accessed and verified the
underlying data. All authors contributed to data analysis and
interpretation, reviewed and critically revised the manuscript, and are
accountable for accuracy and integrity of the work. All authors had full
access to all study data and had the final responsibility for the decision to
submit the publication.
Declaration of interests
AFD reports consulting fees from Cidara. AS reports a grant from
Gilead Sciences and, outside of the submitted work, grant from Pfizer;
consulting fees and honoraria from Angelini, Gilead, Menarini, MSD,
Pfizer, and Shionogi; and support for attending meetings from Pfizer.
BJK reports independent data review committee membership for Cidara.
GRT reports grants and consulting fees from Astellas, Cidara, F2G,
Mayne, Mundipharma, and Scynexis. JAA reports being an employee of
Melinta Therapeutics. JAV reports grants from Cidara and Scynexis;
consulting fees from Cidara and F2G; and data safety monitoring board
or advisory board participation for F2G and Scynexis, outside of the
submitted work. JPH reports consulting fees from Angelini, Menarini,
MSD, Pfizer, Tillots, and Zambon; honoraria from Angelini, Menarini,
and Pfizer; support for attending meetings from MSD and Pfizer; and
data safety monitoring board or advisory board participation for TFT
Pharmaceuticals, outside of the submitted work. MB reports honoraria
from, and data safety monitoring board or advisory board membership
for, Angelini, Astellas, Bayer, Biomerieux, Cidara, Gilead, Menarini,
MSD, Nabriva, and Shionogi, outside of the submitted work.
MH reports grants from Cidara; and outside of the submitted work,
honoraria from Gilead and Pfizer; support for attending meetings from
Gilead, MSD, and Pfizer; and is President of the Belgian Society of
Infectious Diseases. MK reports a grant from Barnes-Jewish Hospital
Foundation, and data safety monitoring board or advisory board
membership for Melinta Therapeutics, outside of the submitted work.
OAC reports grants or contracts from Amplyx, Basilea, BMBF, Cidara,
www.thelancet.com/infection Published online November 23, 2023 https://doi.org/10.1016/S1473-3099(23)00551-0
Articles
DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD,
Mundipharma, Octapharma, Pfizer, and Scynexis; consulting fees from
AbbVie, Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, IQVIA,
Janssen, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC,
Noxxon, Octapharma, Pfizer, PSI, Scynexis, and Seres; honoraria from
Abbott, AbbVie, Al-Jazeera Pharmaceuticals, Astellas, Gilead, Grupo
Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate,
Merck/MSD, Mylan, Noscendo, Pfizer, and Shionogi; payment for expert
testimony from Cidara; a patent at the German Patent and Trade Mark
Office (DE 10 2021 113 007.7); data safety monitoring board or advisory
board participation for Actelion, Allecra, Cidara, Entasis, IQVIA,
Janssen, MedPace, Paratek, PSI, Pulmocide, Shionogi, and The Prime
Meridian Group; stocks from CoRe Consulting and EasyRadiology; and
other interests with Wiley (Editor-in-Chief for Mycoses), outside of the
submitted work. PGP reports grants from Cidara and Scynexis;
consulting fees from Cidara; and data safety monitoring board or
advisory board participation for Cidara, outside of the submitted work.
PMH reports grants or contracts from Baxter, Cytosorbents, and Pfizer;
consulting fees from Baxter, Cytosorbents, and Pfizer; honoraria from
Baxter and Cytosorbents; and support for attending meetings from
Mundipharma and Pfizer, outside of the submitted work. TS reports
being an employee of Cidara Therapeutics; and, outside of the submitted
work, reports being a shareholder in Cidara Therapeutics. All other
authors declare no competing interests.
Data sharing
The study protocols are provided in the supplementary appendices 2 See Online for appendix 2
and 3. Access to anonymised data can be requested by contacting See Online for appendix 3
info@cidara.com. Requests for data can be made beginning 9 months
and ending 36 months following article publication. Each request will be
reviewed by the sponsor for scientific merit.
Acknowledgments
We thank all participants and investigators involved in the studies.
Medical writing support (including development of a draft outline and
subsequent drafts in consultation with the authors, assembling tables
and figures, collating author comments, copyediting, fact checking, and
referencing) was provided by Caroline Greenwood of Aspire Scientific
(Bollington, UK), and funded by Melinta Therapeutics (Parsippany, NJ,
USA). The pooled analysis described in this manuscript was funded by
Cidara Therapeutics and Melinta Therapeutics. The STRIVE study was
funded by Cidara Therapeutics. The ReSTORE study was co-funded by
Cidara Therapeutics and Mundipharma. Rezafungin is being developed
by Cidara Therapeutics (San Diego, CA, USA) in partnership with
Mundipharma (Cambridge, UK). Melinta Therapeutics (Parsippany, NJ,
USA) holds the licence to commercialise rezafungin in the USA.
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