Rezafungin is Noninferior to Caspofungin For All-Cause Mortality in Treating Candida Infections
George Thompson, MD, offers some insights on 2 studies looking at these antifungals in patients with candidemia and invasive candidiasis.
If left unmitigated, Candida can penetrate deeply into the body and develop into fungal infections, including candidemia and invasive candidiasis. These fungal infections can affect the bloodstream and internal organs. Candidemia, in particular, is a common infection found in hospitalized patients. In addition, there are some specific clinical challenges associated with them.
“There's really 2 major problems with candidemia and invasive candidiasis right now. One of them relies on diagnostics. We often don't make the diagnosis of Candida until several days after the infection has manifested. Blood cultures take a little bit to grow; at a minimum, probably 2 days—and that's improved by PCR availability. So, we do get the diagnosis earlier now, but we have to order the correct test, and that's not always done in clinical care,” said George Thompson, MD, professor of Medicine at the University of California, Davis, School of Medicine. “And the other aspect is, even when we do know the diagnosis, the associated mortality rate of candidemia is still high.”
One antifungal looking to address these infections is rezafungin (Rezzayo), which was FDA approved in 2023. It is a long-acting, next-generation echinocandin indicated for the treatment of candidemia and invasive candidiasis. Rezafungin was developed by Cidara Therapeutics, and it’s marketed by Melinta Therapeutics and Mundipharma. Melinta acquired the exclusive rights to commercialize the antifungal in the US. Cidara retains the rights to rezafungin in Japan and has licensed the commercial rights to Melinta Therapeutics in the US and Mundipharma in all other geographies.
The FDA’s approval was largely based on positive data from phase 3 clinical trials. Dosed once a week, rezafungin was determined to be statistically noninferior compared to once-daily caspofungin, the current standard of care.1
Read more: A Long-Acting Injectable for the Treatment of Candida spp Infections
Thompson was part of a team of investigators who conducted a pooled analysis of 2 trials—the phase 2 STRIVE and phase 3 ReSTORE studies— and they examined the all-cause mortality at day 30 of patients with these infections.2
“In STRIVE, rezafungin was found to be efficacious with a similar safety and tolerability profile to that of caspofungin. In ReSTORE, once-weekly rezafungin (using a dosing regimen of 400 mg and 200 mg) was non-inferior for 30-day all-cause mortality to once-daily caspofungin (70 mg and 50 mg), with a similar safety profile,” the investigators wrote.2
One of the important findings that was realized related to the rezafungin dosing regimen as patients treated with this antifungal saw an early benefit.
“It's once a week, so it gets this very high front-loaded exposure more rapidly, clears blood cultures, and probably tissue sites as well,” said Thompson. “In the analysis we saw, the ICU patients actually improved faster in the rezafungin group compared to caspofungin. So all of that makes some sense, I think, just from the PK/PD standpoint, from what we've seen on animal models. And so that was really pretty neat to see it carried forward into the clinical trials and the pooled analysis as well. I think it represents an incremental advance to have rezafungin available for the treatment of those patients.”
Stay tuned for the second installment of the interview this week, as Thompson will discuss patient profiles for rezafungin and prescribing considerations.
