Rezafungin dosed concomitantly with other drugs in the treatment of invasive fungal infections in transplant patients resulted in no significant change in systematic concentrations of the “probe drugs,” according to research to be presented at the 2019 Transplantation and Cellular Therapy Meeting.
“This drug-drug interaction (DDI) study is an important precursor to our upcoming global phase 3 ReSPECT study,” Taylor Sandison, MD, MPH, chief medical officer of Cidara Therapeutics, told Infectious Disease News. “The ReSPECT study is testing rezafungin against other antifungals in the prevention of invasive fungal disease in patients who have undergone allogeneic blood and marrow transplantation (BMT).”
Sandison noted that many current drugs used in this patient population are known to interact with other drugs through metabolic enzymes and transporter pathways, causing drug levels to be too high, which leads to toxicity, or too low, which leads to decreased efficacy.
“The DDI study is meant to inform study sites about potential DDIs with rezafungin by measuring serum levels of drugs that use these CYP and transporter pathways when they are administered alone and then administered with rezafungin,” he said.
Rezafungin is a novel echinocandin antifungal being developed as a once-weekly therapy for candidemia and invasive candidiasis, as well as a prophylactic regimen to protect against common fungal pathogens, according to Cidara.
The prophylaxis development program for IV rezafungin received both fast track and qualified infectious disease product designations from the FDA in September 2018.
In the DDI trial, the researchers studied 26 healthy people to measure DDIs between rezafungin and probe drugs that were selected for known interactions with CYP enzymes and transporters, as well as drugs that were likely to be coadministered with rezafungin. Doses of rezafungin were given on days 1, 10 and 15. Probe drugs were given as part of a cocktail containing at least two drugs before and after receiving rezafungin.
The researchers reported that when they concomitantly dosed rezafungin with metformin, pitavastatin, caffeine, efavirenz, midazolam, digoxin, tacrolimus, repaglinide and rosuvastatin, there was no relevant change in the probe drugs.
They wrote that pharmacokinetic exposures of all drugs were similar whether they were given without or without rezafungin.
“The results of the DDI study tell us that rezafungin has no significant interactions through the most common metabolic and transporter mechanisms,” Sandison said. “Thus, rezafungin can be administered with many other drugs that are metabolized through the CYP enzymes or which use specific transporters without concern for changes in the exposure of other drugs used in the allogeneic BMT population that would lead to toxicity or decreased efficacy of those drugs.”
He added that the study results “provide assurance that rezafungin may be used in this population during the trial and beyond without concerns for affecting the activity of other drugs commonly used in this patient population.” – by John Schoen and Bruce Thiel
Ong V, et al. Poster 535. Presented at: Transplantation and Cellular Therapy Meeting ; Feb. 20-24, 2019 ; Houston.
Disclosures: Sandison reports being an employee and shareholder of Cidara Therapeutics.