Brexafemme (ibrexafungerp) / SCYNEXIS, R-Pharm, GSK, Jiangsu Hansoh Pharma - LARVOL DELTA

Tn-seq screens in Candida glabrata treated with echinocandins and ibrexafungerp reveal pathways of antifungal resistance and cross-resistance. (PubMed, mSphere) - "This study utilizes transposon mutagenesis and deep sequencing (Tn-seq) to explore mechanisms of resistance to four different echinocandins (micafungin, anidulafungin, rezafungin, and caspofungin) and a non-echinocandin inhibitor (ibrexafungerp) of beta-1,3-glucan synthase (GS) in the BG2 strain background. This study investigates how every gene in the pathogenic yeast Candida glabrata contributes to resistance and cross-resistance to all five antifungals of this type. It offers new insights into how each antifungal interacts with the target enzyme and identifies the antifungals where cross-resistance is common or rare, providing guidance on the sequences and combinations that may be most effective in clinical settings."

Journal • Candidiasis

Aspergillosis: A comprehensive review of pathogenesis, drug resistance, and emerging therapeutics. (PubMed, J Food Drug Anal) - "The potential therapeutic benefits of using combination therapy with drug delivery targeting systems and developing new antifungal agents including rezafungin and ibrexafungerp are assessed. The clinical presentation of aspergillosis varies widely which case studies help doctors to understand better. Comprehensive management of aspergillosis necessitates cooperative medical care and precise medicinal interventions alongside continuous diagnostics improvements to achieve solutions for the worldwide health issue."

Journal • Review • Allergy • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Colistin enhances caspofungin antifungal efficacy against Aspergillus fumigatus by modulating calcium homeostasis and stress responses. (PubMed, Nat Commun) - "Here, by screening a collection of 5297 compounds derived from three chemical libraries, we demonstrate that the antibacterial agent colistin (COL) can potentiate the fungistatic echinocandins caspofungin (CAS) and anidulafungin, as well as the structurally distinct cell wall targeting antifungal ibrexafungerp against Aspergillus fumigatus. COL + CAS decreases A. fumigatus infection in human pulmonary cells, Galleria mellonella, and Caenorhabditis elegans. In summary, we demonstrate that the mechanism of COL as a synergizer of CAS against A. fumigatus is the disruption of the cell membrane permeability and calcium homeostasis."

Journal • Infectious Disease

Candida glabrata Prosthetic Joint Infection Managed with Ibrexafungerp. (PubMed, J Fungi (Basel)) - "She initially improved, but relapsed four months post-treatment. This case highlights the potential role of ibrexafungerp in multidrug-resistant Candida infections."

Journal • Candidiasis • Infectious Disease

The future of noninvasive azole antifungal treatment options for the management of vulvovaginal candidiasis. (PubMed, Expert Rev Anti Infect Ther) - "This review focuses on the therapeutic possibilities of VVC with particular interest in the role played by topical antifungal drugs, especially imidazoles, compared to systemic oral treatment with fluconazole, itraconazole, ibrexafungerp or oteseconazole...Although therapeutic tools are increasing, it is important to consider the usefulness of topical drugs, such as clotrimazole and miconazole, which is very relevant in many of these clinical situations. In addition, we must consider that it is also necessary to expand the therapeutic tools with new antifungal agents and formulations, and repurposing current drugs that target these fluconazole-resistant species of Candida."

Journal • Review • Candidiasis • Infectious Disease • Vaginitis

MARIO: A Phase 3, Randomized, Double-blind Study for Patients With Invasive Candidiasis Treated With IV Echinocandin Followed by Either Oral Ibrexafungerp or Oral Fluconazole (clinicaltrials.gov) - P3 | N=220 | Recruiting | Sponsor: Scynexis, Inc. | Suspended ➔ Recruiting | Trial completion date: Aug 2024 ➔ Feb 2027 | Trial primary completion date: Jun 2024 ➔ Dec 2026

Enrollment open • Trial completion date • Trial primary completion date • Candidiasis

Vulvovaginal Candidiasis Caused by Candida krusei (Pichia kudriavzevii), Still a Formidable Challenge. (PubMed, J Low Genit Tract Dis) - "Determining the antifungal susceptibility profile of C. krusei vaginal isolates may be required in selecting effective antifungal treatment of refractory vaginitis due to non-albicans Candida (NAC)."

Journal • Candidiasis • Gynecology • Vaginitis

A Novel Clinical Presentation: First Documented Case of Candida Auris Empyema Thoracis (ATS 2025) - "He was found to have pneumonia due to Pseudomonas, and was treated with parenteral cefepime...He was treated with meropenem, vancomycin, anidulafungin, and liposomal amphotericin B. The pleural C. auris strain was susceptible to anidulafungin (MIC = 0.25 ug/ml)...We await the results of ongoing clinical trials with newly developed phase 2 clinical trial antifungal agents such as fosmanogepix, ibrexafungerp, and T-2307, a novel arylamidine, for advances in anti-C. auris treatment options."

Clinical • Acute Kidney Injury • Diabetes • Diabetic Nephropathy • Infectious Disease • Metabolic Disorders • Pneumonia • Renal Disease • Respiratory Diseases • Septic Shock

Antibiofilm activity of manogepix, ibrexafungerp, amphotericin B, rezafungin, and caspofungin against Candida spp. biofilms of reference and clinical strains. (PubMed, Antimicrob Agents Chemother) - "In conclusion, our in vitro model highlights the antibiofilm activity of novel antifungals against major Candida species, revealing significant differences in efficacy among species. MNGX demonstrated the highest activity, underscoring its potential as a promising candidate for the treatment of biofilm-related infections."

Journal • Infectious Disease

In vitro activity of novel antifungals, natamycin, and terbinafine against Fusarium. (PubMed, Antimicrob Agents Chemother) - "In this article, we assessed the in vitro activity of the novel antifungals olorofim, manogepix, rezafungin, and ibrexafungerp, as well as the established but nonstandard drugs, natamycin and terbinafine, against a large set of molecularly identified clinical Fusarium isolates via EUCAST microdilution. Furthermore, we report specific susceptibilities for terbinafine against FDSC, FFSC, and FOSC species. These findings of complex- and species-specific olorofim and terbinafine in vitro susceptibilities highlight the need for diagnostics below genus level."

Journal • Preclinical • Infectious Disease • Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology

The Impact of Dietary Interventions on the Pharmacokinetics of Antifungal Drugs: A Systematic Review with Meta-analyses. (PubMed, Clin Pharmacokinet) - "Interactions were influenced by such factors as drug physicochemical properties, type of dietary intervention, drug formulation, and patient characteristics. Although the review largely filled the existing gaps in recommendations, we judged the overall quality of evidence as low owing to outdated studies, methodological inconsistencies, and uneven data availability. Further research involving PK/PD indices is needed to link the postprandial changes in the bioavailability of antifungal drugs with their clinical efficacy."

Journal • PK/PD data • Review

Ibrexafungerp prolongs survival and reduces the eumycetoma grain size in Galleria mellonella infection models of two different causative agents of eumycetoma. (PubMed, J Antimicrob Chemother) - "Ibrexafungerp showed in vitro activity and in vivo efficacy against the two most common eumycetoma causative agents."

Journal • Candidiasis • Infectious Disease • Vaginitis

DRUG REGISTRATION APPROVAL OF HENGMEIDA (IBREXAFUNGERP TABLETS) WAS GRANTED BY THE NATIONAL MEDICAL PRODUCTS ADMINISTRATION (Hansoh Pharma Press Release) - "The board of directors (the 'Board') of Hansoh Pharmaceutical Group Company Limited (the 'Company' and together with its subsidiaries, the 'Group') is pleased to announce that, Hengmeida (Ibrexafungerp Tablets) has been granted drug registration approval by the National Medical Products Administration (NMPA) of China for the treatment of vulvovaginal candidiasis (VVC) in adult and post menarche adolescent women."

China approval • Candidiasis

Ibrexafungerp is effective in treatment of patients with candidiasis, including candidaemia, caused by Candida auris: a multicentre, open-label study (CARES) (ESCMID Global 2025) - No abstract available

Clinical • Candidiasis

An open-label study of ibrexafungerp in patients with refractory fungal infections (FURI) (ESCMID Global 2025) - No abstract available

Clinical • Infectious Disease

The GPCR antagonist PPTN synergizes with caspofungin providing increased fungicidal activity against Aspergillus fumigatus. (PubMed, Microbiol Spectr) - "In the model yeast Saccharomyces cerevisiae, heterozygous deletion of genes involved in chromatin remodeling results in PPTN hypersensitivity, and in A. fumigatus, PPTN can have increased fungicidal activity when combined with the histone deacetylase inhibitor trichostatin A and the DNA methyltransferase inhibitor 5-azacytidine. Drug repurposing, where existing drugs are deployed for other clinical indications, has increasingly been used in the process of drug discovery. Here, we show that 4-[4-(4-Piperidinyl) phenyl]-7-[4-(-(trifluoromethyl) phenyl]-2-naphthalenecarboxylic acid (PPTN), a highly specific antagonist of the human P2Y14 receptor, when combined with caspofungin (CAS), ibrexafungerp, voriconazole (VOR), and amphotericin can increase the fungicidal activity against not only A. fumigatus CAS- and VOR-resistant clinical isolates but also CAS against Candida spp."

Journal • Immunology • Infectious Disease • Malaria • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Identification and antifungal susceptibility patterns of reference yeast strains to novel and conventional agents: a comparative study using CLSI, EUCAST and Sensititre YeastOne methods. (PubMed, JAC Antimicrob Resist) - "The compounds with the greatest in vitro activity, as indicated by the lowest geometric mean MIC (GM), were manogepix (GM: 0.01), isavuconazole (GM: 0.05) and rezafungin (GM: 0.03-0.07). The overall essential agreement (EA) (within ±0 to ±2 2-fold dilutions) between the reference methods, EUCAST and CLSI, was 95%, with results ranging from 82% (ibrexafungerp) to 100% (amphotericin B, anidulafungin, fluconazole, 5-flucytosine and micafungin)...However, the differences in EA, particularly for ibrexafungerp and 5-flucytosine, highlight the importance of continued evaluation of these methodologies to ensure consistency. Given that antifungal susceptibility testing plays a critical role in treatment decisions, understanding these variations is essential to prevent potential misclassification of susceptibility profiles, which could impact clinical outcomes."

Journal

Antifungal pipeline: New tools for the treatment of mycoses. (PubMed, Rev Iberoam Micol) - "New antifungal agents, such as ibrexafungerp, rezafungin, oteseconazole, and miltefosine, offer novel mechanisms of action along with reduced toxicity...This review provides a comprehensive overview of these new agents and their mechanisms, and explores the challenges and roles of antifungal drugs in LMICs, where the burden of fungal infections is high. Continued research and development are essential to address the rising incidence and resistance of fungal infections globally."

Journal • Dermatology • Infectious Disease

An update on newer antifungals. (PubMed, Expert Rev Anti Infect Ther) - "New antifungal agents hold promising future for difficult-to-treat fungal infections, providing for improved bioavailability, pharmacokinetic properties, adverse events and drug interactions, as well as, spectrum of activity. However, further data is needed before incorporating these agents in everyday clinical practice for the management of invasive fungal infections."

Journal • Review • Candidiasis • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Vulvovaginal Candidiasis-An Overview of Current Trends and the Latest Treatment Strategies. (PubMed, Microb Pathog) - "Oteseconazole and ibrexafungerp show promise and have the potential to change RVVC therapy. While useful, probiotics generally supplement standard antifungal methods. In conclusion, tackling the growing difficulties of VVC necessitates ongoing research, novel therapeutics, and possible vaccine development in order to reduce the significant worldwide burden presented by this common fungal illness."

Journal • Review • Candidiasis • Diabetes • Infectious Disease • Metabolic Disorders • Vaginitis

Ibrexafungerp for the treatment of vulvovaginal candidiasis: A systematic review and meta-analysis of randomized placebo-controlled trials. (PubMed, J Mycol Med) - "This study provides robust support for the efficacy of ibrexafungerp in the treatment of VVC. While the safety profile of ibrexafungerp appears favorable with mostly mild adverse events reported, decision-making in the clinical context should be guided by individual patient factors."

Journal • Retrospective data • Candidiasis • Infectious Disease • Vaginitis

New Ground in Antifungal Discovery and Therapy for Invasive Fungal Infections: Innovations, Challenges, and Future Directions. (PubMed, J Fungi (Basel)) - "With the increasing incidence of resistance pathogens, such as Candida auris and Aspergillus fumigatus, we assess emerging antifungal agents, including Ibrexafungerp, T-2307, and N'-Phenylhydrazides, which target diverse fungal cell mechanisms. Finally, we briefly examine the potential use of artificial intelligence (AI) in the development of new antifungal treatments, diagnoses, and resistance prediction, which provides powerful tools in the fight against fungal pathogens. Overall, we highlight the pressing need for continued research to advance antifungal treatments and improve outcomes for high-risk populations."

Journal • Review • Infectious Disease

New pharmacotherapeutic strategies for drug-resistant candida infections: a review. (PubMed, Expert Opin Pharmacother) - "This review with discuss the various Candida species, especially the non-albicans species, some of the important mechanisms of resistance, and newer in vitro and clinical studies describing the recent and novel antifungal options such as rezafungin, ibrexafungerp, and oteseconazole, along with a novel antifungal, fosmanogepix. The newer and novel antifungals discussed here will add valuable tools to our antifungal armamentarium to be able to appropriately and adequately treat and manage these difficult infections. Each of the antifungals has unique and novel properties that will expand the arsenal useful to treat these fungal infections in the years to come."

Journal • Review • Candidiasis • Infectious Disease

Fungerps: discovery of the glucan synthase inhibitor enfumafungin and development of a new class of antifungal triterpene glycosides. (PubMed, Nat Prod Rep) - "This highlight will cover the discovery of enfumafungin, its biosynthesis and the characterisation of its antifungal profile and mode of action that led to the development of ibrexafungerp. We will discuss the challenges encountered during this long preclinical program and the clinical trial validation of this first-in-class oral antifungal approved to treat vulvovaginal candidiasis with an enormous therapeutic potential to treat future major threatening drug-resistant fungal pathogens."

Journal • Review • Candidiasis • Infectious Disease • Vaginitis

The Candida auris Infection After the COVID-19 Pandemic Seems to be an Urgent Public Health Emergency: A Call to Attention. (PubMed, Health Sci Rep) - "These resistances were traced back to multiple-point mutations in certain genes, such as ERG11 in the case of fluconazole and amphotericin B. In addition, C. auris is phylogenetically related to C. haemulonii, an emerging pathogen notably resistant to antifungals...Newly developed antifungal agents, like Ibrexafungerp, showed promising results against echinocandin-resistant strains in clinical trials. Without vaccines and effective treatment, its capacity to mutate and spread has detrimental effects on humans. Therefore, extensive research on drug development, quick, reliable diagnosis, and effective strategies for disease prevention and treatment are required to mitigate the health impact of C. auris."

Journal • Dermatology • Infectious Disease • Novel Coronavirus Disease • ERG