The first data readout from a phase 3 trial of Scynexis’ ibrexafungerp has come in, and at first glance looks very positive for the first-in-class antifungal.
The results come from the first 20 of a planned 60 patients in the FURI trial, which is focusing on invasive yeast infections caused by Candida species in patients that have failed multiple antifungal therapies and are at high risk of dying. It showed that oral dosing of ibrexafungerp (previously known as SCY-078) as a "salvage" therapy showed evidence of efficacy in 17 of them, with 11 complete or partial responders and six people whose disease stabilized.
Fungal infections claim an estimated 1.5 million deaths each year, but only a handful of drug classes have been successfully developed for the treatment of life-threatening, invasive fungal diseases including polyenes like amphotericin B, azoles such as fluconazole and echinocandins including Merck’s Cancidas (caspofungin) and Astellas’ Mycamine (micafungin).
That means there is an undeniable need for new treatment options, particularly as some fungal species such as Candida glabrata and C. auris have been identified that are resistant to both azoles and echinocandins. The FURI trial mainly involved infections caused by C. glabrata and C. krusei, organisms prone to antimicrobial resistance.
Ibrexafungerp is a member of the glucan synthase inhibitor class but has a novel triterpenoid structure that Scynexis says combines high antifungal activity with the potential to be delivered both intravenously and orally.
Last October, Scynexis started another phase 3 trial specifically in resistant C. auris infections, which have a mortality rate of up to 60%, with a read-out from that trial due in the coming months. It also has positive mid-stage data in vulvovaginal candidiasis (VVC) and invasive candidiasis (IC).
Analysts Michael Higgins and Rui Galvao of Ladenburg Thalmann think these two studies could lead to accelerated approval from the FDA via the agency’s limited population antimicrobial drug (LPAD) pathway for drugs that treat “serious or life threatening infections in limited populations of patients with unmet needs.” They think a filing could be possible in early 2020 with an approval later in the same year.
“Despite the limited scope of LPAD approvals, we believe there would be significant off-label use,” the analysts write in a research note, pointing out that ibrexafungerp was successful at the interim phase 3 stage “despite challenging odds.”
Two other antifungals have been approved via the LPAD rote, namely Cancidas and Astellas’ triazole Cresemba (isavuconazole).
Scynexis CEO Marco Taglietti said the data “met all of our goals,” including the ethical responsibility to justify the testing of oral ibrexafungerp in these patients and showing that it is effective in treating mucocutaneous and invasive fungal infections that do not respond to other therapies, including those administered intravenously.
He added that it backs up ibrexafungerp’s potential role as “a transformative antifungal agent able to address significant unmet needs in both outpatient and hospital settings in a variety of indications.”