Ibrexafungerp advances the fight against fungus
IV compound enters Phase 1, following FDA Priority Review and Fast Track designations for oral formulation
JERSEY CITY, NJ—In December, SCYNEXIS Inc. reported progress on ibrexafungerp’s intravenous (IV) formulation and provided an update on the therapy’s ongoing Phase 3 studies in the hospital setting. SCYNEXIS has completed preclinical testing of its liposomal IV formulation of ibrexafungerp, and is moving the program into human trials in South Africa.
The Phase 1 trial will evaluate the safety, tolerability, and pharmacokinetics of IV ibrexafungerp in healthy subjects. SCYNEXIS has been granted approvals from the health authority and ethics committee, and the company plans to start dosing in the first quarter of 2021.
SCYNEXIS has collected data from another 43 patients who have completed treatment in the FURI and CARES open-label studies. A Data Review Committee of independent experts is assessing the efficacy of oral ibrexafungerp in this combined third interim analysis. The FURI study is evaluating oral ibrexafungerp as a salvage treatment in patients with a variety of difficult-to-treat mucocutaneous and invasive fungal infections that are refractory to or intolerant of current standards of care, or that require a non-azole oral step-down therapy for treatment of azole-resistant species.
“Ibrexafungerp targets a specific protein responsible for making the fungal cell wall (glucan synthase),” explains Dr. Marco Taglietti, president and CEO of SCYNEXIS. “While another class of antifungals—the echinocandins—also targets this enzyme, ibrexafungerp targets a structurally distinct region, and to date there has been no evidence of cross resistivity. Echinocandins are also only available intravenously, limiting its potential use as a long-term or out-patient treatment option.”
“Ibrexafungerp’s oral formulation is ideal for long treatment durations, so it can potentially be used as an oral step-down after IV echinocandins for patients with azole-resistant infections. To date, our preclinical and toxicology data may suggest that ibrexafungerp has a similar safety and efficacy profile in both oral and IV administration routes,” he adds. “However, an IV formulation would allow us to reach the most vulnerable patients in the hospital setting that are commonly the victims of severe fungal infections.”
The CARES study is focused on hospitalized patients with invasive candidiasis caused by multidrug-resistant Candida auris. SCYNEXIS plans to report results on this group of patients in the first quarter of 2021, bringing the total data set to 84 patients from FURI and CARES. The company has designed each study to support a potential future New Drug Application (NDA) submission through the FDA’s Limited Population Pathway for Antibacterial and Antifungal Drugs program.
“As we prepare for our first commercial launch of oral ibrexafungerp in the community setting in 2021, we are also excited about advancing ibrexafungerp for patients with serious and life-threatening infections in the hospital setting,” Taglietti said. “The analysis of our CARES study will provide the first clinical trial data of an investigational treatment against Candida auris, a multidrug-resistant fungus deemed an urgent threat by the CDC.”
“Ibrexafungerp has been shown in multiple preclinical and clinical settings to be effective against a broad range of pathogens, even against the most drug-resistant fungal strains. At SCYNEXIS, we believe that now more than ever, there is a growing need for innovation in the anti-infective field to combat the threat of evolving pathogens today to prevent a pandemic tomorrow,” he notes.
SCYNEXIS has also reported that the FDA accepted ibrexafungerp’s NDA for the treatment of vulvovaginal candidiasis (VVC). The FDA granted this application Priority Review, and has set a target action date of June 1, 2021.
“The acceptance of this NDA marks a major milestone toward our goal of bringing to market the first new class of antifungals in over 20 years, and the first new oral treatment in more than 25 years, to the millions of women suffering from vaginal yeast infections,” Taglietti pointed out. “As the first oral, non-azole treatment for this particularly symptomatic condition, we believe ibrexafungerp has the potential to change the antifungal treatment landscape.”
The NDA is supported by positive results from two Phase 3 studies (VANISH-303 and VANISH-306), in which oral ibrexafungerp demonstrated statistically superior efficacy and a favorable tolerability profile in VVC.
“To date, ibrexafungerp has shown relevant attributes for treatment of vaginal yeast infections, such as enhanced activity at low vaginal pH, broad-spectrum activity including fluconazole-resistant Candida strains, and high vaginal tissue penetration,” says Taglietti, noting that unlike antifungals such as fluconazole, which are fungistatic, ibrexafungerp is actually fungicidal.
“Enrollment is ongoing in our Phase 3 CANDLE study evaluating oral ibrexafungerp for the prevention of recurrent vaginal yeast infections ... We expect to share top-line results and submit a second NDA for this indication in the second half of 2021,” he comments.
The FDA has granted ibrexafungerp Qualified Infectious Disease Product (QIDP) and Fast Track designations for treatment of VVC, and prevention of recurrent VVC. Under QIDP designation, ibrexafungerp will receive five years of market exclusivity, in addition to five years of exclusivity as a new chemical entity.
“The FDA acceptance and priority review of the NDA for oral ibrexafungerp for the treatment of vaginal yeast infections is a significant milestone both for the company and treatment landscape,” Taglietti continues. “We are continuing preparations for a U.S. commercial launch for the second half of 2021, pending FDA approval.
“In parallel, given the almost 15 years of exclusivity of this novel agent, we continue to advance other indications—as label expansion in VVC with the prevention of recurrent VVC in the second half of 2021, [and] also as a critical medication to treat severe, and often life-threatening, fungal infections in the hospital setting. We believe ibrexafungerp can have a significant impact in multiple segments and become a critical franchise in the world of fungal infections.”