Ibrexafungerp, a Novel Oral Antifungal, Demonstrates No Reproductive or Developmental Harm in Preclinical Models [25J]

Abstract

INTRODUCTION: The treatment of fungal infections, like Vulvovaginal Candidiasis (VVC), during pregnancy is difficult due to the teratogenicity associated with existing anti-fungal treatment options. VVC, also known as yeast infection, is especially common during pregnancy. Fluconazole, the oral standard of care, is not approved for use in pregnancy due to safety concerns. Ibrexafungerp (formerly SCY-078) is a novel triterpenoid glucan synthase inhibitor, with proven anti-fungal activity against Candida, Aspergillus, and Pneumocystis spp. in development for the treatment of fungal infections, including VVC. METHODS: A full developmental and reproductive toxicity package for ibrexafungerp was recently conducted in rats and/or rabbits as required for approval and labeling of prescription medications. These preclinical studies included evaluation of the effect of ibrexafungerp on a) fertility and libido of adult males and females during treatment: b) effects on conception, implantation, and development of embryos; c) development of fetuses; d) parturition, survival, lactation; and the development of offspring from birth through sexual maturation; e) the ability of the offspring to mate and conceive a second-generation post exposure. RESULTS: The studies indicate that ibrexafungerp does not result in reproductive harm to adult animals nor does it result in developmental harm to offspring. CONCLUSION: With proven anti-fungal activity against a broad spectrum of pathogenic fungi, ibrexafungerp shows great promise in treating fungal infections. The lack of reproductive harm in these animal studies provide support for ibrexafungerp as an alternative treatment of fungal infections in women of child-bearing age.

Investigational Agents for the Treatment of Resistant Yeasts and Molds

“…Although it is a CYP2C8 inhibitor, this effect is unlikely to be clinically significant [22]. Additionally, IBX did not show evidence of reproductive harm in animal models [23].…”

Beyond fluconazole

“…Although there are no adequate or well-controlled studies, retrospective epidemiologic studies suggest that the use of fl uconazole in pregnancy may be linked to spontaneous abortion and congenital abnormalities. [39][40][41][42] In a recent meta-analysis, Budani and colleagues found a statistically signifi cant correlation between maternal use of fl uconazole at any dose during the fi rst trimester and heart defects in the off spring. 39 Th e authors of the meta-analysis state that fl uconazole should be considered a human teratogen.…”

“…43 However, as fl uconazole is not approved for use in pregnancy due to safety concerns, use of fl uconazole during pregnancy should be carefully considered with the potential risks explained to the mother. 40 In the last 6 weeks of pregnancy, women with VVC should receive topical azole treatment aimed at reducing the risk of vertical transmission, including resultant oral thrush and diaper dermatitis in the newborn. 21 Fluconazole and topical azoles are compatible with lactation.…”

“…In contrast, according to the seminal essential resource Briggs Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk , the risk of adverse outcomes associated with the use of small doses of fluconazole, such as the amount used to treat an isolated VVC infection, is low 43. However, as fluconazole is not approved for use in pregnancy due to safety concerns, use of fluconazole during pregnancy should be carefully considered with the potential risks explained to the mother 40…”