Antifungal: Rezafungin

Cidara has developed 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 were specifically designed to improve upon a clinically validated mechanism, enhancing its efficacy and safety potential for patients.

All Articles

Press Releases

In the News

Universal coverage against influenza

A single subcutaneous dose of CD377 is highly potent against strains of influenza responsible for pandemics in a lethal influenza mouse model.

REFERENCE: Efficacy of CD377, a Novel Antiviral Fc-Conjugate, Against Seasonal Influenza in Lethal Mouse Models [ECCMID 2020 Abstract 5793]

Long-term, single dose protection

A single dose of CD377 demonstrated potential for long-term protection in mice subjected to pandemic strains of influenza.

REFERENCE: Preclinical Efficacy, Pharmacokinetics, and Safety of CD377, a Novel Antiviral Fc-Conjugate Against Influenza [ECCMID 2020 Abstract 5126]

Efficacy with multiple routes of administration

Single 0.1 mg/kg intravenous (IV), intramuscular (IM) and subcutaneous (SC) doses of CD377 afford equivalent protection in mice dosed 2 hours post infection.

Lower resistance

CD377 demonstrated a lower resistance potential compared to approved influenza treatments, baloxavir and oseltamivir, against a pandemic strain of influenza.

REFERENCE: CD377, a Novel Antiviral Fc-Conjugate, Demonstrates a Lower Resistance Potential than Baloxavir and Oseltamivir against Pandemic Influenza A/H1N1 [ECCMID 2020 Abstract 5707]

Serial Passage (MOI 0.01)

Improved efficacy window

CD377 extends the treatment window, demonstrating improved efficacy with a single dose three days post-infection compared to multiple doses of Tamiflu starting at three days post-infection in a lethal influenza mouse model.

Rapid onset of efficacy

A single dose of CD377 is immediately elevated in both plasma and epithelial lining fluid (ELF) in mice.

Rezafungin is a novel, once-weekly antifungal being developed for the treatment and prevention of serious fungal infections.

Rezafungin is a member of the echinocandin drug class, which is considered to be the safest class of antifungals and the suggested first-line treatment of fungal infections by the Infectious Diseases Society of America (ISDA). Rezafungin’s structure and properties have been precisely refined to retain the safety benefits of echinocandin drugs while enhancing its pharmacokinetic and pharmacodynamic properties to create a longer-lasting, next-generation treatment and preventative, capable of addressing even drug-resistant species.

Rezafungin’s structure yields greater stability, allowing for an extended half-life and improved safety profile.

To date, data demonstrate that rezafungin has potent antifungal activity against representative strains of Candida spp., Aspergillus spp., Pneumocystis spp. and Dermatophytes. In addition, rezafungin has potent activity against fungal pathogens designated as Urgent and Serious by the CDC

Source: Diagnostic Microbiology and Infectious Disease. The PATH (Prospective Antifungal Therapy) Alliance registry and invasive fungal infections: update 2012

An ongoing Phase 3 trial (ReSTORE; NCT03667690) is examining rezafungin for the treatment of fungal infections caused by Candida spp., including candidemia and invasive candidiasis.

An ongoing Phase 3 trial (ReSPECT; NCT04368559) is examining rezafungin for the prevention of fungal infections, caused by Candida, Aspergillus and Pneumocystis, in patients undergoing allogeneic blood and marrow transplant.

The U.S. Food and Drug Administration (FDA) has designated rezafungin as a Qualified Infectious Disease Product (QIDP) Fast Track Product and orphan drug for the treatment of candidemia and invasive candidiasis. The 7-year period of marketing exclusivity provided through orphan designation combined with an additional 5 years of marketing exclusivity provided by the QIDP designation positions rezafungin for a potential total of 12 years of marketing exclusivity to be granted at the time of FDA approval.

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 here.

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 and was statistically superior to currently approved echinocandin caspofungin with a shorter time to negative blood culture.

The STRIVE Phase 2 study evaluated the safety, tolerability and efficacy of once-weekly dosing of rezafungin compared to once-daily dosing of caspofungin 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). Rezafungin demonstrated superiority on time to negative blood culture compared to caspofungin (log-rank test combining both rezafungin groups vs. caspofungin, p = 0.02).

Ongoing trials

Cidara’s ReSTORE trial (NCT03667690) is an ongoing, global, randomized, double-blind, controlled, Phase 3 pivotal study to evaluate the safety, efficacy and tolerability of rezafungin compared to caspofungin for the treatment of candidemia and invasive candidiasis in approximately 184 qualifying patients. The primary efficacy outcome measure for the FDA is All-Cause Mortality at Day 30, while Global Cure at Day 14 is the primary efficacy outcome measure for the EMA.

Every year, an estimated 1.5 million people with compromised or suppressed immune systems die worldwide of invasive fungal infection. For such patients, preventing infection from developing in the first place with antifungal prevention is increasingly important.

Patients who have received a blood and marrow transplant (BMT), cancer chemotherapy or solid organ transplant may receive prophylaxis to prevent deadly Candida, Aspergillus and/or Pneumocystis infections for several weeks to over a year, depending on the period of immunosuppression or development of Graft Versus Host Disease. Current paradigms for the prevention of invasive fungal disease are complex because they require patient-specific plans and drug cocktails, dictated by the underlying disease and the local epidemiology of fungal infections which may be subject to change even when customized.

Rezafungin’s prolonged half-life and tolerability as an echinocandin allows for once-weekly intravenous (IV) administration to more safely prevent Candida, Aspergillus and Pneumocystis infections, including those of drug-resistant species. This confers a significant advantage for patients and physicians over the current standard of care where there is no one agent approved against all three fungi. With these benefits, rezafungin has potential to:

Be a single-agent for prophylaxis of several fungal pathogens – Candida, Aspergillus and Pneumocystis, displacing more toxic azoles and trimethoprim/sulfamethoxazole (TMP/SMX)

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 prophylaxis

Ongoing trials

Cidara’s ReSPECT trial (NCT04368559) is a global, randomized, double-blind, controlled, pivotal Phase 3 trial of rezafungin versus the standard antimicrobial regimen to prevent invasive fungal disease due to Candida, Aspergillus and Pneumocystis in subjects undergoing allogeneic BMT. Rezafungin, dosed once-weekly, will be compared to a daily regimen containing multiple drugs including fluconazole or posaconazole, and trimethoprim-sulfamethoxazole, also known as Bactrim, for 90 days, at which time fungal-free survival will be measured as the primary efficacy outcome. The trial will enroll approximately 462 adults with underlying conditions, such as acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, myelodysplastic syndrome(s), lymphoma and aplastic anemia, across approximately 30 BMT centers.