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

Structural-guided identification of two modulators of β-1,3-glucan synthase FKS1. (PubMed, Nat Commun) - "FKS1 is a β-1,3-glucan synthase critical for fungal cell wall formation and a target for antifungal drugs such as echinocandin and ibrexafungerp...Evolutionarily conserved GSR1 is found to increase the stability of FKS1 in β-1,3-glucan biosynthesis. Collectively, our findings identify both tRNA and GSR1 as intrinsic modulators of β-1,3-glucan biosynthesis, thereby providing opportunities for the further development of FKS1-targeted antifungal drugs."

Journal

Invasive mould infection in children - advances made or obstacles remaining? (PubMed, Clin Microbiol Infect) - "There has been much progress in IMI management with recent development of novel diagnostic methods, new antifungals, and immunotherapeutic approaches. Ongoing paediatric studies are required to inform optimal implementation of these tools into clinical practice."

IO biomarker • Journal • Review • Infectious Disease • Pediatrics • Pulmonary Disease • Respiratory Diseases

Fungal β-1,3-Glucan Synthase: A Review of Structure, Mechanism, and Regulation. (PubMed, FEMS Yeast Res) - "Fungal β-1,3-glucan synthase (Fks) plays a central role in synthesizing β-1,3-glucan, the main structural polysaccharide of fungal cell walls, and serves as a key target for antifungal drugs such as echinocandins and ibrexafungerp...In addition, we present a potential gating model of β-glucan translocation and drug-inhibition by integrating literature with structure-based analyses. This review provides a structure-based functional model of fungal β-1,3-glucan synthase and the putative binding mechanism of its inhibitor, aiming to support future antifungal drug discovery."

Journal

SCYNEXIS Completes Transfer of BREXAFEMME New Drug Application to GSK (The Manila Times) - "'...GSK will be able to initiate regulatory interactions with the U.S. Food and Drug Administration (FDA) to discuss the relaunch of BREXAFEMME for vulvovaginal candidiasis (VVC) and refractory vulvovaginal candidiasis (rVVC) in the U.S. market.'"

FDA filing • Candidiasis • Infectious Disease

First report of Candida (Candidozyma) auris infections in a human and a dolphin from the Dominican Republic: A One health perspective. (PubMed, Med Mycol Case Rep) - "Antifungal susceptibility testing from dolphin isolate showed elevated minimum inhibitory concentrations (MIC) of fluconazole but low MICs of other antifungals, including the novel drugs rezafungin, ibrexafungerp and manogepix. Whole genome sequencing (WGS) of the dolphin isolate allocated it to clade I, but surprisingly did not show any known mutations that confer azole resistance, suggesting a mechanism different from mutations in the genes studied. The concurrent emergence of C. auris in human and animal hosts underscores the importance of a One Health approach, emphasizing the interconnectedness of human, animal, and environmental health, and the need for strengthened surveillance and rigorous infection control measures across medical and veterinary settings."

Journal • Infectious Disease

Management of invasive candidiasis in the ICU: Challenges and advances (Review). (PubMed, Med Int (Lond)) - "Improvements in innovative diagnostic methods, including rapid molecular testing, as well as developments in antifungal therapy, such as rezafungin and ibrexafungerp, help improve patient outcomes. The present review also discusses clinical guidelines emphasizing the need for early empirical therapy, species-specific definitive treatment, and proper treatment duration. Continuous research toward new diagnostic procedures, antifungal agents and vaccines is essential to overcoming the challenges posed by IC in critically ill patients."

Journal • Review • Candidiasis • Critical care • Infectious Disease

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=68 | Active, not recruiting | Sponsor: Scynexis, Inc. | Recruiting ➔ Active, not recruiting | N=220 ➔ 68

Enrollment change • Enrollment closed • Candidiasis

Optimizing Antifungal Therapies for Candida Infections: Evidence, Resistance, and Emerging Approaches. (PubMed, Clin Microbiol Infect) - "The increasing burden of antifungal resistance highlights the need for optimized therapeutic strategies and improved diagnostic tools. Combination therapies and novel antifungals offer promising alternatives, but further research is essential to evaluate their clinical efficacy. Strengthening antifungal stewardship programs and enhancing surveillance for resistance patterns are critical to managing Candida infections effectively and mitigating the public health threat posed by resistant strains."

Journal • Review • Candidiasis • Infectious Disease

New and emerging drugs for the treatment of invasive fungal infections. (PubMed, Expert Opin Pharmacother) - "Data were identified using PubMed searches for the terms 'antifungal,' 'olorofim,' 'SUBA-itraconazole,' 'ibrexafungerp,' 'rezafungin,' 'fosmanogepix,' and 'encochleated amphotericin B.' Approved agents include ibrexafungerp, an oral triterpenoid inhibitor of 1,3-β-D-glucan synthase; rezafungin, a long-acting echinocandin with weekly dosing; and SUBA-itraconazole, a reformulation of itraconazole with more consistent absorption. Despite improvements, gaps remain in treatments for severe IFI, particularly given increasing resistance. These agents represent significant advances, but further research is needed to define their use in patient management."

Journal • Review • Dermatology • Infectious Disease

Ibrexafungerp: Mechanism of Action, Clinical, and Translational Science. (PubMed, Clin Transl Sci) - P2, P3 | "We reviewed the regulatory approval process of ibrexafungerp, including key clinical trials and in-depth analyses of pivotal studies related to the drug's clinical efficacy and safety. Additionally, we reviewed the drug's unique mechanism of action and the pharmacokinetic and pharmacodynamic characteristics essential for its use in VVC and RVVC."

Journal • Review • Candidiasis • Pain • Pediatrics • Pulmonary Disease • Respiratory Diseases • Vaginitis

In Vitro Evaluation of Ibrexafungerp Against Clinical and Environmental Isolates of Cryptococcus neoformans and Cryptococcus gattii. (PubMed, J Glob Antimicrob Resist) - No abstract available

Journal • Preclinical

Engineered Fusion Enzyme-Mediated Non-Consecutive Cyclization-Glycosylation Enables Heterologous Synthesis of Antifungal Enfumafungin. (PubMed, Adv Sci (Weinh)) - "Notably, ibrexafungerp, a semi-chemically synthesized analogue of enfumafungin, has recently received approval as a novel antifungal drug...Conversely, a designed fusion enzyme EfuA(TC)FsoA(GT), which combines the TC domain of EfuA with the GT domain of FsoA (involved in fuscoatroside biosynthesis), along with FsoD/E/F, efficiently produced the putative enfumafungin intermediate. The functional analysis further revealed that while the fusion of the TC and GT domains is critical for maintaining dual enzymatic activity, these fusion enzymes catalyze unconventional, non-consecutive terpene cyclization and glycosylation steps during the biosynthesis of enfumafungin-type antibiotics, differing from other canonical fusion enzymes."

Journal

Clinical impact of fluconazole-resistant Candida parapsilosis: a narrative review. (PubMed, Future Microbiol) - "Treatment options are limited: echinocandins and liposomal amphotericin B (L-AmB) are commonly used alternatives, but their use is challenged by intrinsic and emerging echinocandin resistance and L-AmB toxicity and cost. Novel agents such as rezafungin, fosmanogepix, and ibrexafungerp have shown promising activity against fluconazole-resistant C. parapsilosis, though further clinical studies are needed to confirm their efficacy. This narrative review aims to summarize current evidence on the epidemiology, clinical implications, and therapeutic approaches for fluconazole-resistant C. parapsilosis infections."

Journal • Review • Infectious Disease

Antifungal Agents in the 21st Century: Advances, Challenges, and Future Perspectives. (PubMed, Infect Dis Rep) - "Promising developments include next-generation echinocandins (e.g., rezafungin), triterpenoids (ibrexafungerp), and orotomides (olorofim), which target resistant strains and offer improved safety profiles. The review also highlights the critical role of "One Health" strategies to mitigate environmental and clinical resistance. Future success hinges on multidisciplinary collaboration, enhanced surveillance, and accelerated drug development to address unmet needs in antifungal therapy."

Journal • Review • Infectious Disease

Draft genome sequence and annotation of the enfumafungin producing fungus Hormonema carpetanum ATCC 74360. (PubMed, BMC Genom Data) - "Enfumafungin is a fernane-type triterpenoid glycoside compound with broad-spectrum antifungal activity, and this leading compound has been developed to antifungal agent ibrexafungerp approved by Food and Drug Administration (FDA)...antiSMASH predicted biosynthesis gene cluster (BGC) of secondary metabolite, including enfumafungin BGC. This genome and related data files presented here will provide a foundation for further gene editing of this important antibiotic-producing microorganism."

Journal • Metabolic Dysfunction-Associated Steatohepatitis

Real-World Ibrexafungerp Use Patterns Among Patients with Commercial Health Insurance, United States, 2021-2023. (PubMed, Drugs Real World Outcomes) - "Our results suggest that ibrexafungerp was generally used as non-first-line treatment for VVC."

Journal • Real-world evidence • Reimbursement • US reimbursement • Candidiasis • Gynecology • Vaginitis

A Phase 3, multicenter, randomized, placebo-controlled trial of monthly oral ibrexafungerp to reduce the incidence of recurrent vulvovaginal candidiasis. (PubMed, Am J Obstet Gynecol) - "Once-monthly oral ibrexafungerp was effective and well-tolerated in participants with recurrent vulvovaginal candidiasis."

Journal • P3 data • Candidiasis • Infectious Disease • Pain • Vaginitis

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