Antifungal: Rezafungin

Cidara is developing a novel once-weekly echinocandin, rezafungin, for both the treatment and prevention of serious fungal infections, such as candidemia and invasive candidiasis. The structure and properties of rezafungin are specifically designed to improve upon a clinically validated mechanism, enhancing its efficacy and safety potential for patients.

Overview

Treatment

Prevention

Over 90% of invasive fungal infections begin in the hospital. Infections caused by the Candida fungus – candidemia (bloodstream infection) and invasive candidiasis (focal infection localized to an organ) – comprise the majority of these invasive fungal infections. Unfortunately, high rates of morbidity and mortality, on top of high medical costs are associated with invasive Candida infections.

Today’s treatments for invasive fungal disease, including polyenes, azoles and currently approved echinocandins, have significant limitations. Toxicities, drug-drug interactions, low or variable exposure, daily intravenous administration and increasing resistance to treatment are all issues that can complicate therapy in patients who are already clinically complex and very ill.

To learn more about invasive Candida infections, visit the CDC website.

Over 90% of invasive fungal infections begin in the hospital. Infections caused by the Candida fungus – candidemia (bloodstream infection) and invasive candidiasis (focal infection localized to an organ) – comprise the majority of these invasive fungal infections. Unfortunately, high rates of morbidity and mortality, on top of high medical costs are associated with invasive Candida infections.

Today’s treatments for invasive fungal disease, including polyenes, azoles and currently approved echinocandins, have significant limitations. Toxicities, drug-drug interactions, low or variable exposure, daily intravenous administration and increasing resistance to treatment are all issues that can complicate therapy in patients who are already clinically complex and very ill.

To learn more about invasive Candida infections, visit the CDC website.

Rezafungin’s high plasma exposure and extended half-life allows for front-loaded, once-weekly intravenous (IV) dosing to treat Candida infections, including those caused by drug-resistant species. This confers a significant advantage for patients and physicians compared to currently approved echinocandins administered IV once-daily. With this benefit, rezafungin has potential to:

Provide superior clearance of Candida from the bloodstream early in the course of infection

Treat invasive disease and less susceptible pathogens by achieving high drug exposures in humans

Be the only echinocandin to facilitate shorter and less costly hospital stays

Be the only echinocandin to provide more cost-effective and compliant outpatient echinocandin therapy

Phase 2 STRIVE trial data showed that rezafungin met all of its objectives for safety, efficacy and tolerability in the treatment of patients with candidemia and/or invasive candidiasis.

The STRIVE Phase 2 study evaluated the safety, tolerability and efficacy of once-weekly dosing of rezafungin (RZF) compared to once-daily dosing of caspofungin (CAS) in patients with candidemia and/or invasive candidiasis. The study evaluated two IV dosing regimens of either 400 mg of rezafungin administered once weekly (400/400) or 400 mg on week one, then 200 mg once weekly thereafter (400/200). For the primary endpoint, the RZF 400/200 mg group had a higher rate of overall cure at day 14 compared with other groups. For the secondary endpoint of all-cause mortality (ACM) at day 30, the lowest rate observed was in the RZF 400/200 mg group. True cure rates with indeterminate responses excluded, such as for the primary efficacy endpoint of overall response, were 81.4% for RZF 400/200 mg, 69.7% for rezafungin 400 mg, and 70.7% for CAS. Rezafungin demonstrated superiority on time to negative blood culture compared to caspofungin (log-rank test combining both rezafungin groups vs. caspofungin, p = 0.02).

Recently Completed Trial

Cidara’s ReSTORE trial (NCT03667690) is a recently completed, global, randomized, double-blind, controlled, Phase 3 pivotal study that evaluated the safety, efficacy and tolerability of rezafungin compared to caspofungin for the treatment of candidemia and invasive candidiasis in approximately 187 qualifying patients. Topline results of the study demonstrate that rezafungin met the primary objective of non-inferiority for the U.S. Food and Drug Administration (FDA) on All-Cause Mortality at Day 30 and also met the primary objective for the European Medicines Agency (EMA) on Global Cure at Day 14.