Mundipharma and Cidara Therapeutics, Inc. today presented data from the Phase 3 ReSTORE clinical trial of rezafungin in the treatment of candidemia and/or invasive candidiasis at the 32nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).
The data, presented in a late-breaking poster, showed non-inferiority for rezafungin dosed once-weekly compared to caspofungin, the current standard of care, dosed once-daily, for both primary endpoints.
Results from ReSTORE showed the primary endpoints were met with:
- 23.7% all-cause mortality on day 30 for rezafungin compared to 21.3% for caspofungin (difference, 2.4; 95% CI for risk difference -9.7 to 14.4*)
- global cure on day 14 of 59.1% for rezafungin and 60.6% for caspofungin (difference, -1.1; 95% CI for risk difference -14.9* to 12.7)
- *To meet the pre-specified limit of non-inferiority, the upper (for all-cause mortality) and lower (for global cure) 95% confidence limits for the difference between arms must be within 20%. Both endpoints met the pre-specified 20% limit, establishing non-inferiority.
Further data from the ReSTORE trial demonstrated high rates of early mycological efficacy with rezafungin:
- negative blood culture at 24 hours was 53.7% for rezafungin versus 46.2% for caspofungin and 74.2% versus 64.1% at 48 hours
- median time to negative blood culture was 23.9 hours for rezafungin versus 27.0 hours for caspofungin (p=0.175)
Additional data from an oral late-breaking presentation at ECCMID from an integrated analysis of the Phase 2 STRIVE and Phase 3 ReSTORE data of rezafungin in the treatment of candidemia and/or invasive candidiasis, supports the analysis of ReSTORE:
- 18.7% all-cause mortality on day 30 for rezafungin compared to 19.4% for caspofungin (weighted mortality difference, -1.5%; 95% CI: -10.7 to 7.7, stratified analysis by study)
- percentage of subjects with negative blood culture at 24 hours was 60.0% for rezafungin versus 49.1% for caspofungin and 77.7% versus 63.5% at 48 hours
- median time to negative blood culture was 22.3 hours for rezafungin versus 26.3 hours for caspofungin (p=0.0051)
Both the STRIVE and ReSTORE trials demonstrated similar tolerability outcomes for rezafungin and caspofungin and did not reveal any concerning trends in TEAEs or SAEs.
Further data presented at ECCMID assessing the pharmacokinetics of drug interactions between rezafungin and anticancer agents venetoclax or ibrutinib demonstrated that in subjects receiving multiple drug interventions, rezafungin can be given with no dose adjustments due to pharmacokinetics.
“The results of both the STRIVE and ReSTORE trials, as well as the pharmacokinetics data, provide clear evidence of the potential impact that rezafungin could have for patients fighting serious and hard to treat invasive Candida infections,” said Jeffrey Stein, Ph.D., president and chief executive officer of Cidara. “We look forward to submitting our NDA to the FDA in mid-2022 and subsequent ex-US submissions, and to making a difference in the lives of patients.”
Oliver Cornely, investigator in the ReSTORE trial and Professor of Internal Medicine at the University of Cologne, Germany, added: “As the mortality rate for patients with invasive candidiasis remains high there is a real unmet need for new treatment options to address this serious disease. Rezafungin could be the first new treatment option for patients with candidemia or invasive candidiasis for over 10 years.”
Brian Sheehan, Ph.D., Chief Scientific Officer at Mundipharma, said: “We are extremely pleased that these data presented today may help pave the way for once-weekly rezafungin to help critically ill patients with invasive Candida infections. The results from these important trials provide initial evidence that the unique pharmacokinetic/pharmacodynamic profile of rezafungin may lead to quicker fungal clearance for patients with Candida infections.”
Cidara has partnered with Mundipharma who has commercial rights to rezafungin outside the U.S. and Japan.