Lack of Effect of Rezafungin on QT/QTc Interval in Healthy Subjects

Flanagan, Shawn D.; Goodman, Daniel B.; Jandourek, Alena; O’Reilly, Terry; Sandison, Taylor

doi:10.1002/cpdd.757

Cited by 20 publications

(11 citation statements)

References 22 publications

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“…Preclinical studies have established the efficacy of RZF in animal models of candidemia, IC, and Candida biofilms [ 5 , 9 , 12–15 ]. In addition, phase 1 studies have demonstrated the safety and tolerability of RZF in healthy volunteers [ 11 , 16 ]. Here we present the results of STRIVE, a phase 2 trial designed to evaluate the safety and efficacy of intravenous (IV) RZF, compared with caspofungin (CAS) and optional oral fluconazole stepdown therapy, in the treatment of candidemia/IC.…”

mentioning

confidence: 99%

Rezafungin Versus Caspofungin in a Phase 2, Randomized, Double-blind Study for the Treatment of Candidemia and Invasive Candidiasis: The STRIVE Trial

Thompson

Soriano

Skoutelis

et al. 2020

Clinical Infectious Diseases

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Background Rezafungin (RZF) is a novel echinocandin exhibiting distinctive pharmacokinetics/pharmacodynamics. STRIVE was a phase 2, double-blind, randomized trial designed to compare the safety and efficacy of RZF once weekly (QWk) to caspofungin (CAS) once daily for treatment of candidemia and/or invasive candidiasis (IC). Methods Adults with systemic signs and mycological confirmation of candidemia and/or IC were randomized to RZF 400 mg QWk (400 mg), RZF 400 mg on week 1 then 200 mg QWk (400/200 mg), or CAS 70 mg as a loading dose followed by 50 mg daily for ≤ 4 weeks. Efficacy assessments included overall cure (resolution of signs of candidemia/IC + mycological eradication) at day 14 (primary endpoint), investigator-assessed clinical response at day 14, and 30-day all-cause mortality (ACM) (secondary endpoints), and time to negative blood culture. Safety was evaluated by adverse events and ACM through follow-up. Results Of 207 patients enrolled, 183 were in the microbiological intent-to-treat population (~21% IC). Overall cure rates were 60.5% (46/76) for RZF 400 mg, 76.1% (35/46) for RZF 400/200 mg, and 67.2% (41/61) for CAS; investigator-assessed clinical cure rates were 69.7% (53/76), 80.4% (37/46), and 70.5% (43/61), respectively. 30-day ACM was 15.8% for RZF 400 mg, 4.4% for RZF 400/200 mg, and 13.1% for CAS. Candidemia was cleared in 19.5 and 22.8 hours in RZF and CAS patients, respectively. No concerning safety trends were observed; ACM through follow-up was 15.2% (21/138) for RZF and 18.8% (13/69) for CAS. Conclusions RZF was safe and efficacious in the treatment of candidemia and/or IC.

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confidence: 99%

Rezafungin Versus Caspofungin in a Phase 2, Randomized, Double-blind Study for the Treatment of Candidemia and Invasive Candidiasis: The STRIVE Trial

Thompson

Soriano

Skoutelis

et al. 2020

Clinical Infectious Diseases

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“…In addition, a randomized, double-blind, phase I study was conducted in healthy volunteers to evaluate cardiac effects of single doses of intravenous rezafungin [ 203 ]. For echinocandins, data on QT prolongation among echinocandins are limited.…”

Section: Antifungal Drugs In Clinical Developmentmentioning

confidence: 99%

The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin

Hoenigl

Sprute

Egger

et al. 2021

Drugs

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The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug–drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available over the last 2 decades, and only one single new agent from a known antifungal class has been approved in the last decade. Nevertheless, there is hope on the horizon, with a number of new antifungal classes in late-stage clinical development. In this review, we describe the mechanisms of drug resistance employed by fungi and extensively discuss the most promising drugs in development, including fosmanogepix (a novel Gwt1 enzyme inhibitor), ibrexafungerp (a first-in-class triterpenoid), olorofim (a novel dihyroorotate dehydrogenase enzyme inhibitor), opelconazole (a novel triazole optimized for inhalation), and rezafungin (an echinocandin designed to be dosed once weekly). We focus on the mechanism of action and pharmacokinetics, as well as the spectrum of activity and stages of clinical development. We also highlight the potential future role of these drugs and unmet needs. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01611-0.

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“…An additional phase 1 study has shown no effect on QTc or other aspects of the cardiac electrical rhythm (Flanagan et al, 2020).…”

Section: Clinical Datamentioning

confidence: 96%

“…This data has subsequently been used to develop a population level PK model ( Lakota et al., 2018 ). An additional phase 1 study has shown no effect on QTc or other aspects of the cardiac electrical rhythm ( Flanagan et al., 2020 ).…”

Section: Rezafungin (Cidara)mentioning

confidence: 99%

Antifungal Pipeline

McCarty

Pappas

2021

Front. Cell. Infect. Microbiol.

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In many ways, fungal diseases are forgotten or neglected. Given the significantly lower frequency compared to similar bacterial etiologies across the spectrum of infectious syndromes, it makes sense that anti-bacterial agents have seen the bulk of development in recent decades. The vast majority of new antifungal medications approved for use in the past 10 years have been new versions in the same class as existing agents. Clinical mycology is crying out for new mechanisms of action in the setting of rising resistance and emergence of new organisms. Fortunately, this trend appears to be reversing. There are numerous agents in advanced stages of development offering novel dosing regimens and mechanisms of action to combat these threats. Herein we review seven antifungal agents that we hope to see come to market in the coming years to aid physicians in the treatment of mucocutaneous and invasive fungal infections.

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Lack of Effect of Rezafungin on QT/QTc Interval in Healthy Subjects

Cited by 20 publications

References 22 publications

Rezafungin Versus Caspofungin in a Phase 2, Randomized, Double-blind Study for the Treatment of Candidemia and Invasive Candidiasis: The STRIVE Trial

Rezafungin Versus Caspofungin in a Phase 2, Randomized, Double-blind Study for the Treatment of Candidemia and Invasive Candidiasis: The STRIVE Trial

The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin

Antifungal Pipeline

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