General Information

Rezzayo (rezafungin) is an echinocandin antifungal.

Rezzayo is specifically indicated for the treatment of candidemia and invasive candidiasis in people 18 years of age and older with limited or no alternative treatment options.

Rezzayo is supplied as a solution for intravenous administration. Administer the recommended dosage of Rezzayo once weekly, with an initial 400 mg loading dose, followed by a 200 mg dose once weekly thereafter. The safety of Rezzayo has not been established beyond 4 weekly doses.

Missed Doses

If a scheduled dose is missed (not taken on the assigned day), administer the missed dose as soon as possible.

If the missed dose is administered within 3 days of the assigned day, the next weekly dose may be given on schedule.

If the missed dose is administered more than 3 days after the assigned day, revise the dosing schedule to ensure there are at least 4 days before the next dose.

If restarting after at least 2 weeks of missed dosing, the dosing should be started again at the 400 mg loading dose.

Mechanism of Action

Rezafungin is a semi-synthetic echinocandin. Rezafungin inhibits the 1,3-B-D-glucan synthase enzyme complex, which is present in fungal cell walls but not in mammalian cells. This results in inhibition of the formation of 1,3-B-D-glucan, an essential component of the fungal cell wall of many fungi, including Candida species (spp.). Inhibition of 1,3-B-D-glucan synthesis results in concentration-dependent in vitro fungicidal activity against Candida spp., however, the clinical significance of this activity is unknown.

Clinical Trial Results

FDA approval was based on clinical data from Cidara’s global ReSTORE Phase 3 trial and supported by the STRIVE Phase 2 clinical trial and extensive non-clinical development program. In clinical studies, Rezzayo, dosed once-weekly, met the FDA and EMA primary endpoints, demonstrating statistical non-inferiority versus caspofungin, a current once-daily standard of care.

ReSTORE was a global, double-blind, double-dummy, randomized trial in adults (≥18 years) with systemic signs and mycological confirmation of candidemia or invasive candidiasis. Patients were assigned (1:1) to receive intravenous rezafungin once a week (400 mg in week 1, followed by 200 mg weekly, for a total of two to four doses) or intravenous caspofungin (70 mg loading dose on day 1, followed by 50 mg daily) for no more than 4 weeks. The primary endpoints were global cure (consisting of clinical cure, radiological cure, and mycological eradication) at day 14 for the European Medical Agency (EMA) and 30-day all-cause mortality for the US Food and Drug Administration (FDA), both with a target non-inferiority margin of 20%, assessed in the modified intention-to-treat population (all patients who received one or more doses of study drug and had documented Candida infection). Results: 55 (59%) of 93 patients in the rezafungin group and 57 (61%) of 94 patients in the caspofungin group had a global cure at day 14 (weighted treatment difference −1·1%; EMA primary endpoint). 22 (24%) of 93 patients in the rezafungin group and 20 (21%) of 94 patients in the caspofungin group died or had an unknown survival status at day 30 (treatment difference 2·4%; FDA primary endpoint).

STRIVE was a double-blind, randomized trial designed to compare the safety and efficacy of once weekly Rezafungin (RZF) to caspofungin (CAS) once daily for treatment of candidemia and/or invasive candidiasis (IC). Adults were randomized to RZF 400 mg once weekly (400 mg), RZF 400 mg on week 1 then 200 mg once weekly (400/200 mg), or CAS 70 mg as a loading dose followed by 50 mg daily for ≤4 weeks. The primary endpoint was overall cure (resolution of signs of candidemia/IC + mycological eradication) at day 14. 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. Additionally, investigator-assessed clinical cure rates were 69.7% (53/76), 80.4% (37/46), and 70.5% (43/61), respectively. In total, 30-day all cause mortality 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.