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

Reassessment of the role of combination antifungal therapy in the current era. (PubMed, Curr Opin Infect Dis) - "There is a need to investigate the use of combination antifungal agents. This includes delineating the indication of these combined antifungal therapies and determining how to use them most appropriately in the clinical setting."

Journal • CNS Disorders • Infectious Disease • Pulmonary Disease • Respiratory Diseases

A review of the fernane-type triterpenoids as anti-fungal drugs. (PubMed, Front Pharmacol) - "Ibrexafungerp was a novel, highly bioavailable glucan synthase inhibitor formulated for both intravenous and oral administration being developed by Scynexis; it was also the first novel anti-fungal drug class approved in more than 20 years...In addition, the review summarized the progress of enzymes responsible for the biosynthesis of type II fernane triterpenoid (enfumafungin skeleton) and type I fernane triterpenoid (polytolypin skeleton). The good example kept our confidence up for searching for new leading compounds and discovering drugs from fungi."

Journal • Review • Infectious Disease

Activity of Ibrexafungerp and Comparator Antifungals Tested against Candida and Aspergillus Isolates Collected from Invasive Infections in a Global Surveillance Program in 2023 (IDWeek 2024) - No abstract available

Clinical • Infectious Disease

SCYNERGIA: Evaluate Safety and Efficacy of the Coadministration of Ibrexafungerp With Voriconazole in Patients With Invasive Pulmonary Aspergillosis (clinicaltrials.gov) - P2 | N=22 | Terminated | Sponsor: Scynexis, Inc. | Completed ➔ Terminated; Enrollment took longer than anticipated (slow enrollment during COVID).

Trial termination • Myelodysplastic Syndrome • Neutropenia • Pulmonary Disease • Respiratory Diseases

Innovative therapies for treatment of invasive fungal diseases (PubMed, Laryngorhinootologie) - "This review aims to give a comprehensive overview of emerging treatment strategies.Novel drugs in development are Ibrexafungerp, an orally available triterpenoid inhibiting glucan synthesis, and Rezafungin representing the echinocandins with extended half-life and improved tissue penetration, both recently licensed for certain indications. Fosmanogepix targets glycosylphosphatidylinositol biosynthesis, while Olorofim, an orotomide, inhibits fungal nucleic acid synthesis, both currently assessed in advanced clinical trials.Immunotherapeutic approaches include immune checkpoint inhibitors to enhance immune response in immunosuppressed individuals and fungal-specific allogeneic CAR-T cell therapy...have been discovered but are not yet seen in clinical trials. Vaccines against distinct fungal antigens as well as pan fungal vaccines to prevent IFD are under development in preclinical stages, notably for Candida spp., Cryptococcus spp., and Aspergillus spp., however, their..."

Journal • Infectious Disease • Oncology

Repurposing therapy of ibrexafungerp vulvovaginal candidiasis drugs as cancer therapeutics. (PubMed, Front Pharmacol) - No abstract available

Journal • Candidiasis • Oncology • Vaginitis

Brilacidin, a host defense peptide mimetic, potentiates ibrexafungerp antifungal activity against the human pathogenic fungus Aspergillus fumigatus. (PubMed, Microbiol Spectr) - "BRI + IBX can inhibit the growth of A. fumigatus voriconazole- and caspofungin-resistant clinical isolates. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. We propose the combination of BRI and IBX as a new antifungal combinatorial treatment against aspergillosis."

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

Pharmacokinetic evaluation of ibrexafungerp for the treatment of vulvovaginal candidiasis and beyond. (PubMed, Expert Opin Drug Metab Toxicol) - "The evidence involving the utilization of ibrexafungerp for the treatment of VVC shows that it is superior when compared to placebo and has comparable clinical cure rates when compared with fluconazole. For VVC, a dose of 300 mg (two 150 mg tablets) twice daily is recommended and does not require dose adjustments based on renal or hepatic function. The use of ibrexafungerp outside of VVC is currently under study with several ongoing trials showing promising interim data."

Journal • PK/PD data • Review • Candidiasis • Vaginitis

A cost-effectiveness analysis of the use of oral ibrexafungerp versus fluconazole for acute vulvovaginal candidiasis in the UK NHS primary care service. (PubMed, Br J Gen Pract) - "This analysis highlights fluconazole's cost-effectiveness in current UK guidelines and favourability."

Clinical • Cost effectiveness • HEOR • Journal • Review • Candidiasis • Infectious Disease • Inflammation • Vaginitis

Antifungal pipeline: Is there light at the end of the tunnel? (PubMed, World J Clin Cases) - "This editorial critically examines the current clinical landscape and spotlights emerging antifungal agents, such as Fosmanogepix, Ibrexafungerp, and Olorofim, while also unraveling the multifaceted challenges faced in new antifungal drug development. Their future role hinges on thorough clinical validation, cost-effectiveness assessments, and continuous post-marketing surveillance. Only through strategic implementation and integration with market strategies we can transform the landscape of antifungal development, addressing both the resistance crisis and the treatment challenges."

Journal

Ibrexafungerp: A narrative overview. (PubMed, Curr Res Microb Sci) - "Clinical trials showed that IBX was effective and non-inferior to fluconazole in treating vulvovaginal candidiasis (VVC), including complicated cases, as well as in preventing its recurrence. Mild adverse reactions have been reported including gastrointestinal symptoms. Overall, IBX represents a significant addition to the antifungal armamentarium, with its unique action, spectrum of activity, and encouraging clinical trial results warranting further investigation."

Journal • Review • Candidiasis • Gastrointestinal Disorder • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Vaginitis

A Mini-Review of In Vitro Data for Candida Species, Including C. auris, Isolated during Clinical Trials of Three New Antifungals: Fosmanogepix, Ibrexafungerp, and Rezafungin. (PubMed, J Fungi (Basel)) - "In conclusion, this mini-review summarizes insights regarding clinical outcomes and the in vitro activity of three new antifungals against Candida spp. cultured from patients in clinical trials."

Journal • Preclinical • Review • Infectious Disease

In Vitro Activity of Ibrexafungerp against Emerging and Cryptic Aspergillus Species Isolated from Hospitalized Patients with Underlying Primary Immunodeficiencies (ASM Microbe 2024) - "Our data demonstrate that ibrexafungerp has a potent in vitro activity against all emerging clinically important cryptic members of the genera Aspergillus. In vivo animal studies are warranted to further confirm the efficacy of ibrexafungerp against these species using animal model of IA, either as a monotherapy or in combination with other systemic antifungals."

Preclinical • Immunology • Primary Immunodeficiency • Pulmonary Disease • Respiratory Diseases

Management of invasive candidiasis: A focus on rezafungin, ibrexafungerp, and fosmanogepix. (PubMed, Pharmacotherapy) - "Lastly, fosmanogepix, a mechanistically novel, investigational antifungal agent, may be a potential future option in the management of IC and candidemia. Future research is needed to evaluate the potential use of these agents among diverse patient populations."

Journal • Review • Candidiasis • Infectious Disease • Vaginitis

Ibrexafungerp as Salvage Therapy for Candida Glabrata Fungemia in a Pediatric Patient with Multivisceral Transplant (ATC 2024) - "He was maintained on tacrolimus and prednisone. Ibrexafungerp may serve as an effective oral option for salvage therapy for multi-drug resistant C. glabrata fungemia. Further studies are needed to assess optimal duration."

Clinical • Candidiasis • Hepatology • Infectious Disease • Pediatrics • Transplantation • Vaginitis

Interactive Symposium - Fungal Infections and Novel Antifungals in Transplantation (ATC 2024) - "Fosmanogepix, Ibrexafungerp, Olorofim, and Rezafungin are new antifungals. Tran. The moderators will present challenging cases of invasive fungal infections in solid organ transplant recipients, and in these settings, the speakers will discuss the data on novel antifungal therapies."

Infectious Disease • Solid Organ Transplantation • Transplantation

Innovative therapies for treatment of invasive fungal diseases (PubMed, Dtsch Med Wochenschr) - "This review aims to give a comprehensive overview of emerging treatment strategies.Novel drugs in development are Ibrexafungerp, an orally available triterpenoid inhibiting glucan synthesis, and Rezafungin representing the echinocandins with extended half-life and improved tissue penetration, both recently licensed for certain indications. Fosmanogepix targets glycosylphosphatidylinositol biosynthesis, while Olorofim, an orotomide, inhibits fungal nucleic acid synthesis, both currently assessed in advanced clinical trials.Immunotherapeutic approaches include immune checkpoint inhibitors to enhance immune response in immunosuppressed individuals and fungal-specific allogeneic CAR-T cell therapy...have been discovered but are not yet seen in clinical trials. Vaccines against distinct fungal antigens as well as pan fungal vaccines to prevent IFD are under development in preclinical stages, notably for Candida spp., Cryptococcus spp., and Aspergillus spp., however, their..."

Journal • Review • Infectious Disease • Oncology

Biosynthesis of Enfumafungin-type Antibiotic Reveals an Unusual Enzymatic Fusion Pattern and Unprecedented C-C Bond Cleavage. (PubMed, J Am Chem Soc) - "These compounds exhibit significant antifungal properties with ibrexafungerp, a semisynthetic derivative of enfumafungin, recently gaining FDA's approval as the first oral antifungal drug for treating invasive vulvar candidiasis...FsoE is a P450 enzyme that catalyzes successive oxidation reactions at C19 to facilitate a C-C bond cleavage, producing an oxidized carboxyl group and a reduced methyl group that have never been observed in known P450 enzymes. Our study thus sets the important foundation for the manufacture of enfumafungin-type antibiotics using biosynthetic approaches."

Journal • Candidiasis • Solid Tumor

In vitro challenge of ibrexafungerp versus echinocandin-resistant clinical Candida species (ECCMID 2024) - No abstract available

Preclinical

Efficacy and safety of ibrexafungerp in the treatment of vulvovaginal candidiasis: A meta-analysis of randomized controlled trials. (PubMed, Heliyon) - "When ibrexafungerp was compared to fluconazole/placebo, the duration of any treatment-related treatment-emergent adverse events (TEAE), nausea, and diarrhea during therapy was significantly longer. In summary, the use of ibrexafungerp was linked to superior clinical cure ratio, and mycological eradication when compared to fluconazole/placebo."

Journal • Retrospective data • Candidiasis • Infectious Disease • Vaginitis

Ibrexafungerp is efficacious in a neutropenic murine model of pulmonary mucormycosis as monotherapy and combined with liposomal amphotericin B. (PubMed, Antimicrob Agents Chemother) - "Treatment with placebo (diluent control), ibrexafungerp (30 mg/kg, PO BID), liposomal amphotericin B (LAMB 10 mg/kg IV QD), posaconazole (PSC 30 mg/kg PO QD), or a combination of ibrexafungerp plus LAMB or ibrexafungerp plus PSC began 16 h post-infection and continued for 7 days for ibrexafungerp or PSC and through day 4 for LAMB. Monotherapies also reduce the lung and brain fungal burden by ~0.5-1.0log10 conidial equivalents (CE)/g of tissue vs placebo in mice infected with R. delemar (P < 0.05), while a combination of ibrexafungerp plus LAMB lowered the fungal burden by ~0.5-1.5log10 CE/g compared to placebo or any of the monotherapy groups (P < 0.03). These results are promising and warrant continued investigation of ibrexafungerp as a novel treatment option against mucormycosis."

Journal • Monotherapy • Preclinical • Infectious Disease

Efficacy and safety of ibrexafungerp in the treatment of vulvovaginal candidiasis: a systematic review and meta–analysis (ECCMID 2024) - No abstract available

Retrospective data • Review • Candidiasis • Vaginitis

Efficacy and safety of oral ibrexafungerp in Chinese patients with vulvovaginal candidiasis: a phase III, randomized, double-blind study. (PubMed, Infection) - "As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG."

Clinical • Journal • P3 data • Candidiasis • Gastrointestinal Disorder • Vaginitis

Fluconazole-resistant Candida parapsilosis genotypes from hospitals located in five Spanish cities and one in Italy: Description of azole-resistance profiles associated with the Y132F ERG11p substitution. (PubMed, Mycoses) - "We detected a recent clonal spread of fluconazole-resistant C. parapsilosis across some cities in Spain, mostly driven by dominating city-specific genotypes, which involved a large number of isolates harbouring the Y132F ERG11p substitution. Isolates harbouring substitution Y132F can be suspected because they are non-susceptible to voriconazole and rarely posaconazole-resistant."

Journal

Targeting Fks1 proteins for novel antifungal drug discovery. (PubMed, Trends Pharmacol Sci) - "Here, we discuss the role of Fks1 in the survival and adaptation of fungi, guided by insights from evolutionary and structural analyses. Furthermore, we delve into the dynamics of Fks1 modulation with novel antifungal strategies and assess its potential as an antifungal drug target."

Journal • Review • Infectious Disease