Rezafungin Elicits Non-Inferior Outcomes to Caspofungin in Treating a Serious Fungal Infection

The use of rezafungin was associated with comparable clinical efficacy and safety vs caspofungin in patients with candidemia or invasive candidiasis, according to data from the phase 3 ReSTORE trial (NCT03667690).

Invasive candidiasis, according to the CDC, is a serious infection that can affect the blood, heart, brain, eyes, bones or other parts of the body. Anyone can develop the infection, but certain individuals are at a greater risk. For instance, the CDC notes that patients with weakened immune systems—including patients receiving chemotherapy for cancer or who have low white blood cell counts as a result of cancer treatment—have a greater likelihood of developing the serious infection.

Here, investigators assessed rezafungin and caspofungin on 2 primary end points: investigator-assessed global cure at day 14 of treatment as mandated by the European Medicines Agency (EMA), and the 30-day all-cause mortality rate as mandated by the FDA.

Of the enrolled patients, 59% (n = 55/93) of those treated with rezafungin and 61% (n = 57/94) of those treated with caspofungin achieved a global cure at day 14; there was a weighted treatment difference of –1.1% between patient cohorts (95% CI, –14.9%-12.7%). Moreover, 24% (n = 22/93) of patients in the rezafungin group and 21% (n = 20/94) of those in the caspofungin cohort died or had an unknown survival status at day 30 with a treatment difference of 2.4% between cohorts (95% CI, –9.7%-14.4%).

“Rezafungin is a safe and efficacious agent and does have some pharmacokinetic advantages over the currently available echinocandin class,” lead study author George R. Thompson, MD, a professor of Clinical Medicine at UC Davis School of Medicine in Sacramento, California, said in an interview with CancerNetwork^®. “And the data that's going to come out over the next few years is going to further add to populations that would really benefit from rezafungin.”

Thompson noted the difference between the two treatments and suggested how rezafungin may be a better option for patients with cancer who develop candidemia or invasive candidiasis.

“Having just a once-a-week dosing possibility is very convenient for healthcare staff and also patients,” he said. “[Rezafungin] also might avoid some of the drug interactions with that come up with some of the non-echinocandin antifungals that we do use in patients [with cancer].”

Investigators of the multi-center, double-blind, randomized trial conducted research across 66 tertiary care centers in 15 countries. Patients were randomly assigned 1:1 to either receive 400 mg of intravenous rezafungin in week 1 followed by 200 mg weekly for up to 2 to 4 doses or a 70 mg loading dose of intravenous caspofungin on day 1 followed by 50 mg once a day for no more than 4 weeks.

Trial investigators randomly assigned 199 patients (mean age, 61 years; standard deviation, 15.2) to receive either rezafungin (n = 100) or caspofungin (n = 99). In the rezafungin and caspofungin cohorts, respectively, most patients were male (67% vs 57%), White (61% vs 61%), had a diagnosis of candidemia only (70% vs 69%), and had a modified mean Acute Physiology and Chronic Health Evaluation II score of less than 20 (84% vs 83%).

An exploratory end point included the number of patients in the modified intent-to-treat population who had a negative blood sample without subsequent positive cultures at various times following initiation of study treatment. Among patients who received rezafungin or caspofungin, respectively, 54% (n = 36/67) vs 46% (n = 30/65) of patients had a negative blood sample 24 hours after their first dose, and 74% (n = 49/66) vs 64% (n = 41/64) of patients had a negative blood sample 48 hours following their first dose.

In the trial’s safety analysis, at least 1 treatment-emergent adverse effect (TEAE) was observed among 91% (n = 89/98) of patients in the rezafungin cohort and 85% (n = 83/98) of those receiving caspofungin. Serious AEs were observed among 56% and 53% of patients receiving rezafungin and caspofungin, respectively. The most common TEAEs with an incidence of at least 5% observed in each respective cohort included pyrexia (14% vs 5%), hypokalemia (13% vs 9%), septic shock (10% vs 9%), and anemia (9% vs 9%).

Reference

Thompson III GR, Soriano A, Cornely OA, et al. Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial. Lancet Oncol. Published online November 25, 2022. doi:10.1016/S0140-6736(22)02324-8