Latest and emerging therapies for fungal biofilms and systemic infections

The development of novel antifungal agents is critical for addressing systemic and biofilm-associated fungal infections, as current treatment options often show limited efficacy against drug resistance and the protective biofilm barrier. By designing drugs capable of effectively penetrating or disrupting fungal biofilms, antifungal penetration and fungicidal efficiency can be significantly enhanced—thereby improving patient outcomes and reducing infection recurrence. Research on these emerging therapies focuses on integrating pharmacological activity with biofilm-interference mechanisms to overcome the limitation of conventional drugs, which frequently fail to reach the core infection sites. Against this backdrop, we systematically evaluate the therapeutic potential of these candidate agents in treating biofilm-related infections and systemic diseases caused by clinically important fungi, thoroughly investigating their mechanisms of action, efficacy profiles, and potential for clinical translation—to provide a scientific foundation for optimizing future antifungal treatment strategies. Novel Therapies Targeting Candida albicans Given the high incidence of Candida albicans in healthcare-associated infections, antifungal agents targeting its biofilms have become a key research focus. • Rezafungin (rezafungin): prolonged pharmacodynamic effect Rezafungin is an FDA-approved second-generation echinocandin with optimized pharmacokinetic properties. Its half-life reaches up to 130 hours, enabling once-weekly dosing instead of daily administration. Rezafungin disrupts Candida albicans biofilm formation, reduces metabolic activity and thickness of mature biofilms, and inhibits hyphal growth—demonstrating superior activity compared to fluconazole. • Ibrexafungerp: more potent efficacy and reduced resistance risk Ibrexafungerp is a semi-synthetic triterpenoid derived from enfumafungin and represents the first glucan synthase inhibitor with high tissue distribution and excellent oral bioavailability. It exhibits broad-spectrum activity against multiple pathogenic fungi—including Candida albicans—and has received FDA approval for the treatment of vulvovaginal candidiasis (VVC). Although its mechanism of action overlaps partially with that of echinocandins, its distinct binding site minimizes cross-resistance. In vitro studies show that ibrexafungerp reduces biofilm metabolic activity by 50% at just 0.25 µg/mL, whereas fluconazole requires concentrations exceeding 256 µg/mL to achieve the same effect. • Fosmanogepix: attenuates virulence factors of Candida albicans Fosmanogepix is a novel antifungal prodrug converted in vivo by alkaline phosphatase into its active form, manogepix. Phase III clinical trials are currently underway evaluating fosmanogepix for candidemia and invasive candidiasis. It inhibits inositol acetyltransferase Gwt1, thereby interfering with fungal cell wall synthesis and attenuating key virulence factors of Candida albicans—including adhesion, hyphal formation, and biofilm development. With >90% oral bioavailability and broad-spectrum antifungal activity, fosmanogepix shows strong promise as a novel therapeutic agent for systemic infections. • Turbinmicin: reduces biofilm metabolic activity Turbinmicin—a compound discovered from the microbiome of tunicates—targets the Sec14 protein and demonstrates exceptional activity against Candida albicans biofilms. Sec14 plays a critical role in vesicle-mediated delivery within the biofilm matrix.

Hansoh Pharmaceutical’s innovative drug approved for market launch, targeting a RMB 3-billion gynecological anti-infective market!

Recently, Jiangsu Hengrui Medicine Co., Ltd.—a subsidiary of Hansoh Pharmaceutical Group—received approval from China’s National Medical Products Administration (NMPA) for its innovative drug ibrexafungerp citrate tablets, indicated for the treatment of vulvovaginal candidiasis (VVC) in adult and postmenarchal female patients. Source of screenshot: NMPA official website This approval was based on a multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial conducted in China among adult VVC patients to assess the efficacy and safety of HS-10366 (ibrexafungerp citrate). Results demonstrated that the trial met pre-specified superiority criteria for both primary and key secondary endpoints, achieving statistically significant advantages over placebo. Ibrexafungerp citrate tablets represent the first antifungal agent with a novel triterpenoid structure and a new mechanism of action—as a glycogen synthase inhibitor. Both in vitro and in vivo studies have confirmed its broad-spectrum antifungal activity, including efficacy against strains resistant to azoles and echinocandins. Ibrexafungerp citrate was originally developed by SCYNEXIS, Inc. (USA). In February 2021, Hansoh Pharmaceutical entered into a licensing agreement with SCYNEXIS to assume responsibility for the development, regulatory approval, and commercialization of ibrexafungerp citrate in China—including Hong Kong, Macau, and Taiwan. To date, ibrexafungerp citrate has received FDA approval for two indications: treatment of vulvovaginal candidiasis (VVC) and reduction of recurrence rates in recurrent vulvovaginal candidiasis (RVVC).

First antifungal in new class succeeds in Phase 3 trial

23 hours ago

F2G reported Phase 3 success for olorofim, a new-class oral antifungal treating invasive aspergillosis, with mortality rates comparable to standard care and FDA approval anticipated later this year.

cen

2026-10-21

First antifungal in new class succeeds in Phase 3 trial

First antifungal in new class succeeds in Phase 3 trial

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