STRIVE: Rezafungin safe, effective against Candida
Cidara Therapeutics released results of the phase 2 STRIVE trial that showed a once-weekly IV dose of rezafungin was well-tolerated and effective against candidemia and invasive candidiasis.
“This is the first time that any antifungal has shown the potential to be a safe and effective once-weekly treatment option for patients with difficult-to-treat and deadly invasive Candida infections, which may enable patients to leave the hospital earlier, saving money and improving care,” Jeffrey Stein, PhD, president and CEO of Cidara, said in a press release. “With these data in hand, we can confidently select the dosing regimens for our two upcoming phase 3 pivotal trials of rezafungin in treatment and prophylaxis.”
The STRIVE trial evaluated the safety, tolerability and efficacy of IV rezafungin — a novel antifungal echinocandin — in patients with candidemia or invasive candidiasis in North America and Europe. The participants were randomly assigned to 400 mg of rezafungin once weekly for up to 4 weeks; 400 mg of rezafungin followed by 200 mg once weekly for up to 4 weeks; or daily caspofungin. Participants in the IV casopofungin group were given the option to switch to oral fluconazole.
STRIVE met all primary safety and efficacy endpoints, according to the press release. Although the trial was not powered to assess superiority or noninferiority of rezafungin vs. casopofungin, available data from a microbiological intent-to-treat population (n = 92) showed that 75.8% of patients who received 400 mg of rezafungin weekly, 77.4% who received 400 mg then 200 mg of rezafungin weekly, and 71.4% who received caspofungin daily had a clinical cure by day 14. Overall mortality rates were 15.2% in the 400 mg rezafungin arm, 9.7% in the 400 mg/200 mg rezafungin arm and 17.9% in the comparator arm.
In a safety analysis involving 104 patients, 88.6% in the 400 mg rezafungin arm, 94.4% in the 400 mg/200 mg rezafungin arm and 81.8% in the comparator arm reported treatment-emergent adverse events. However, “no concerning trends in adverse events” were observed, the release said. Two serious adverse events possibly related to the study drug occurred in one patient who received 400 mg of rezafungin followed by 200 mg weekly and one patient who received casopofungin. Both patients fully recovered, and no treatment-related deaths were reported.
Rezafungin will be further evaluated in the phase 3 ReSTORE and ReSPECT trials. The ReSTORE trial will investigate rezafungin as a treatment for candidemia or invasive candidiasis, or both, whereas ReSPECT will examine its potential as a prophylactic regimen to prevent Candida, Aspergillus and Pneumocystis in patients undergoing allogenic bone marrow transplantation.
If approved, George Thompson, MD, associated professor of clinical medicine at the University of California, Davis, School of Medicine said rezafungin would be the first new treatment for serious Candida infections and prophylaxis for invasive fungal infections in more than a decade.
“The STRIVE trial results are very promising, and they bring rezafungin one step closer to becoming a potential new and very practical solution for patients and clinicians to address the significant limitations with current standards of care, such as low drug exposure, increasing resistance and daily IV administration that can complicate step-down therapy at discharge,” he said in the release.
Cidara Therapeutics. Cidara Therapeutics Reports Positive Topline Results from Phase 2 STRIVE Trial of Lead Antifungal Rezafungin. 2018. http://ir.cidara.com/phoenix.zhtml?c=253962&p=RssLanding&cat=news&id=2338634. Accessed March 9, 2018.
Disclosures: Stein is president and CEO of Cidara Therapeutics.