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

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

Study of Oral Ibrexafungerp (SCY-078) in Adolescent Female Subjects (clinicaltrialsregister.eu) - P1 | N=6 | Sponsor: SCYNEXIS, Inc.

New P1 trial • Candidiasis • Dermatology • Infectious Disease • Vaginitis

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

Usage of Antifungal Agents in Pediatric Patients Versus Adults: Knowledge and Gaps. (PubMed, Mycopathologia) - "The oral formulations of ibrexafungerp, fosmanogepix and olorofim along with the extended dosing intervals of rezafungin show promising features for effective antifungal treatment in pediatrics. Despite the promising potential of novel antifungal drugs, their performance in heavily immunosuppressed patients remains unstudied. Until then, dedicated antifungal stewardship programs for high-risk patients are essential to optimize therapeutic outcomes, improve patient care, and limit the emergence of resistance."

Journal • Review • Infectious Disease • Pediatrics

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

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