Favorable Results for Ibrexafungerp in Treating Invasive Candidiasis in Phase 2 Study

Oral ibrexafungerp (formerly SCY-078), a novel beta-glucan synthase inhibitor, showed promise as a step-down treatment for invasive candidiasis in a recent phase 2 study.

“The new drug, ibrexafungerp, is likely to be a useful addition to the antifungal armamentarium,” corresponding author Andrej Spec, MD, MSCI, associate professor of infectious disease and associate director of the Infectious Disease-Clinical Research Unit at Washington University in St. Louis Medical Center, told Contagion^®. “It has activity against many resistant forms of fungus, and it can also be given orally, allowing many patients who would require IV therapy to be treated with pills.”

Findings from the multinational, open-label study were published in the Journal of Antimicrobial Therapy. The study found that a 750 mg daily dose of oral ibrexafungerp was well-tolerated and had a response rate similar to the standard of care (oral fluconazole or IV micafungin).

The study treated 7 patients with 500 mg daily of oral ibrexafungerp following an initial 1000 mg loading dose, 7 with 750 mg of oral ibrexafungerp following a 1250 mg loading dose, and 8 with the standard of care. These were tested as step-down treatments after initial intravenous echinocandin therapy. Patients over the age of 18 years with a diagnosis of candidiasis (including candidemia) were included in the study, which was conducted from March 2015 to July 2016. There were 23 participating sites in the United States, 5 in Latin America, and 1 in Germany.

The study found no significant difference in outcomes or safety among the 3 groups.

Pharmacokinetic data suggested better drug exposure from a daily 750 mg dose after a 1250 mg loading dose. The targeted outcome was to maintain exposure of 15.4 μM·h in >80% patients throughout the therapy up to 28 days. Response rates were 86% in the study arm that received 750 mg dosing, and 71% in the other 2 groups.

The most common adverse effects that did not lead to drug discontinuation included mild to moderate abdominal pain, diarrhea, nausea, and vomiting. In total, 2 patients experienced adverse effects related to the study drug. There were 9 patients who experienced serious adverse effects during the study, including 2 deaths that were not drug-related. One death, due to septic shock, occurred in the group receiving the standard of care regimen. The other occurred in the high-dose ibrexafungerp group and was attributed to progression of small cell lung cancer.

“The drug now needs to go into phase 3 trials in order to be approved for use,” Spec said. “This is an exciting prospect because it has the potential to change how we treat many people with invasive candidiasis.”

Candida has raised concerns as a growing threat, raising interest in the development of new treatments.

Ibrexafungerp has demonstrated activity against multidrug-resistant fungal infections. The promising new drug was highlighted earlier this year at the European Congress for Clinical Microbiology and Infectious Diseases (ECCMID 2019).

Coinciding bacterial and fungal infections are another concern, with a recent study finding that nearly 10% of Americans hospitalized for candidemia were coinfected with Clostridioides difficile.

“The most important thing to know is that this drug exists, treats resistant forms, and once it goes through phase 3, it will allow people for much more convenient treatment,” Spec concluded.