Dr. George Thompson On Phase 2 STRIVE Study Evaluating Optimal Dosing for Rezafungin
OCT 04, 2018 | MICHAELA FLEMING
Invasive fungal infections are a serious health threat and cause more than 1.5 million deaths annually. These infections are particularly threatening to immunocompromised populations including cancer and transplant patients.
Rezafungin is a novel echinocandin being developed by Cidara Therapeutics for the treatment of these invasive fungal infections, including candidemia and invasive candidiasis.
“Rezafungin is different from the other agents in its same antifungal class [because of] its really long half-life,” George Thompson, MD, associate professor of clinical medicine at UC Davis Medical Center, and principal investigator of the STRIVE study told Contagion® in a recent interview. “It allows once-weekly dosing which has a lot of potential pharmacokinetic advantages.”
The phase 2 STRIVE study evaluated the safety and efficacy of once-weekly dosing of rezafungin acetate compared with once-daily dosing of caspofungin in participants with mycologically-confirmed candidemia and/or invasive candidiasis.
Data from the Phase 2 STRIVE study is being presented at ID Week 2018 held this year in San Francisco, California. In an interview with Contagion®, Dr. Thompson shared implications of the trial (see video below).
The STRIVE study enrolled a total of 92 participants who were randomly assigned into 1 of 3 treatment groups.
Participants in group 1 received 400 mg of rezafungin administered intravenously (IV) once a week for the duration of 4 weeks; participants in group 2 received 400 mg of rezafungin for the first week followed by 200 mg of rezafungin once a week for the following 3 weeks. In the comparator arm, participants received caspofungin daily with optional criteria-defined oral stepdown after >3 days of IV therapy.
A strong focus of the STRIVE study was to determine the proper dose to be used in phase 3 trials, Dr. Thompson said.
“The dosing regimen that we need to use for rezafungin is very important, and that was hashed out in detail in the STRIVE study,” he said, “It’s really essential to give the maximum dose for efficacy but also to balance that carefully with the side effect profile of the agent.”
In the study, safety and efficacy were evaluated by adverse events related to the treatment and overall success at day 14.
The rate of adverse events was 88.6% in group 1, 94.4% in group 2 and 81.8% in group 3. Severe adverse events occurred in 37.1% of patients in group 1, 27.8% in group 2, and 39.4% in group 3. According to the investigators, there were no concerning trends in adverse events.
The overall mortality rate in the 3 treatment groups was 15.2%, 9.7%, and 17.9%, respectively.
The data indicate that group 2—where individuals were given the dose of 400 mg administered once in week 1 and 200 mg administered once a week for the following 3 weeks—had the highest rate of overall success, with a rate of 71% at day 14.
Rezafungin met the primary objectives of the phase 2 trial in that it was found to be well tolerated and effective, which was defined by clearance of Candida from the blood or other normally sterile sites, resolution of signs related to the infection, and overall survival.
Dr. Thompson discusses the clinical implications of the trial and the advantages of rezafungin in the video below.
“The next steps for rezafungin are to move on to a phase 3 for the treatment of invasive candidiasis; it will look at efficacy as well as toxicity.” Dr. Thompson added. “Also, [another] new study [is] going to look at prophylaxis in the bone marrow transplant population which has some real potential advantages of prophylaxis against yeast, mold, and Pneumocystis.”
Due to the small sample size in the phase 2 trial, a larger phase 3 trial is needed to confirm the findings.
The rezafungin prophylaxis program was recently granted a Qualified Infectious Disease Product (QIPD) and fast track designation by the US Food and Drug Administration (FDA) for adults undergoing allogeneic bone marrow transplantations. In the past, rezafungin received a QIDP designation from the FDA for the treatment of invasive fungal infections caused by Candida.
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Big advances in treatment can't make up for an inability to stop new infections, which number 5,000 per day worldwide.
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