Olorofim (orotomide) / F2G, Shionogi - LARVOL DELTA

WHO Critical Priority Fungi: A Comprehensive Review of Antifungal Resistance, Emerging Therapeutic Strategies, and the Potential of Antifungal Peptides. (PubMed, Int J Mol Sci) - "This review provides a comprehensive overview of the molecular mechanisms underlying resistance to conventional and emerging antimycotics in critical priority fungi, including recently approved and investigational agents such as oteseconazole, rezafungin, ibrexafungerp, fosmanogepix, and olorofim. Special emphasis is placed on antifungal peptides (AFPs) derived from plants, animals, bacteria, and fungi, along with their synthetic analogs, all of which have demonstrated efficacy against critical priority fungi. The review primarily focuses on the molecular targets of AFPs and on the development of fungal resistance under prolonged exposure, compared with conventional antifungals, in order to evaluate their potential as prototypes for next-generation antimycotics."

Journal • Review • Dermatology • Infectious Disease

Long-Term Follow-Up of Study 32 (S32LTFU): A Retrospective Observational Study to Collect Long-Term Follow-Up Data from Patients in Study 32, an Open-Label Single-Arm Phase IIb Study of Olorofim as Treatment of Invasive Fungal Infections due to Lomentospora prolificans, Scedosporium spp., Aspergillus spp., and Other Resistant Fungi in Patients Lacking Suitable Alternative Treatment Options... (IDWeek 2026) - P2 | No abstract available

Observational data • P2b data • Retrospective data • Infectious Disease

Health-Related Quality of Life in Patients with Invasive Fungal Infections with Limited or No Treatment Options: An Analysis of the Phase 2b Olorofim Trial Data (IDWeek 2026) - No abstract available

Clinical • HEOR • P2b data • Infectious Disease

Pathogenesis and Triazole Resistance in Aspergillus fumigatus: A Narrative Review Across the Host Immune Spectrum and One Health Context. (PubMed, Infect Drug Resist) - "Novel antifungal agents, such as olorofim, fosmanogepix, rezafungin, ibrexafungerp, and T-2307, along with targeted delivery and immunomodulatory adjunct therapies for resistant aspergillosis, are also summarized. Major knowledge gaps persist regarding horizontal gene transfer of resistance mutations, cross-species transmission chains, and translational applications of environmental monitoring data. This review summarizes existing research bottlenecks and proposes integrated multi-sector prevention and control strategies from a One Health perspective to curb the growing threat of triazole-resistant aspergillosis."

Journal • Review • Gene Therapies • Pulmonary Disease • Respiratory Diseases • ARAF

Central Nervous System Aspergillosis: Advances in Diagnosis, Therapeutics, and Multidisciplinary Management (2026 Update). (PubMed, Mycoses) - "This review integrates the latest evidence to provide a timely and actionable resource for clinicians. It bridges gaps in existing guidelines by offering a multidisciplinary approach that addresses the complex management of CNS aspergillosis, with particular relevance for high-risk populations such as COVID-19 and immunocompromised patients."

IO biomarker • Journal • Review • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Man-in-the-barrel syndrome caused by cervical arachnoiditis in refractory coccidioidal meningitis. (PubMed, Med Mycol Case Rep) - "The patient was treated sequentially with fluconazole, other azole therapy, liposomal amphotericin B, intrathecal amphotericin B, and olorofim, with only partial disease control. Surgical lysis of adhesions and placement of a spinal Ommaya reservoir for intrathecal amphotericin delivery above and below the obstructed segment resulted in partial neurologic improvement. This case broadens the differential diagnosis of man-in-a-barrel syndrome to include active fungal meningitis with compressive cervical myelopathy and highlights the role of combined surgical-medical management in complicated fungal arachnoiditis."

Journal • CNS Disorders • Infectious Disease • Inflammation

Molecular Mechanisms, Diagnosis, and Therapeutic Strategies of Antifungal Resistance in Filamentous Fungi. (PubMed, J Fungi (Basel)) - "Precision dosing guided by therapeutic drug monitoring, combination therapy, and the introduction of novel agents (including isavuconazole, rezafungin, fosmanogepix, and olorofim) are progressively improving clinical outcomes. Looking ahead, global surveillance and multisectoral collaboration are essential to deepen our understanding of resistance evolution, accelerate the clinical translation of novel diagnostic and therapeutic tools, and curb the global spread of resistance."

Journal • Review

Novel antifungal agents for treating endemic mycoses: hope on the horizon? (PubMed, Curr Opin Infect Dis) - "Growing evidence suggests therapy for endemic mycoses may change substantially in the near future. New drugs and alternative treatment approaches have the potential to improve safety, tolerability, oral availability, drug-drug interaction profiles, and treatment duration, with important implications for both clinical care and future research."

Journal • Dermatology • Respiratory Diseases

Emergence of Trichophyton indotineae: in vitro susceptibility data from a mycology reference laboratory in Australia. (PubMed, JAC Antimicrob Resist) - "Forty-four clinical T. indotineae isolates (cultured from skin, 2005-2025) across several Australian jurisdictions were tested for susceptibility to itraconazole, voriconazole, posaconazole, terbinafine and olorofim using CLSI broth microdilution methodology. Susceptibility testing can inform treatment choice. The azoles and olorofim demonstrate good in vitro activity."

Journal • Preclinical • Dermatology

Emerging antifungal agents in human medicine: Mechanisms, clinical progress, and future perspectives. (PubMed, Eur J Med Chem) - "This narrative review summarizes the current landscape of emerging antifungal therapies, focusing on ibrexafungerp 1, rezafungin 2, fosmanogepix 3, olorofim 4, opelconazole 5, and oteseconazole 6. However, important challenges remain, including limited activity against Mucorales for several agents, the potential emergence of future resistance, and the need for additional comparative clinical data and real-world experience. Overall, the expanding antifungal pipeline represents a major advancement toward more targeted and individualized antifungal therapy and may significantly reshape the future management of invasive and refractory fungal infections."

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

Olorofim in Early Coccidioidal Meningitis (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Fariba Donovan | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Infectious Disease

Olorofim in Treatment of Patients With Poorly Controlled Disseminated Coccidioidomycosis : A Single-Group, Open-Label, Phase 2b, Multicenter Study. (PubMed, Ann Intern Med) - P2 | "Olorofim showed effectiveness in patients with DCM with limited or no therapeutic options. F2G, Ltd."

Clinical • Journal • P2b data • Dermatology • Oncology • Respiratory Diseases

COCCIMETRICS: A Phase II Randomized Study to Evaluate Measures for Endpoint Derivation in Patients With Progressive or Refractory Disseminated Coccidioidomycosis (DCM ) Treated With Olorofim Plus Baseline SOC or Placebo Plus Baseline SOC (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: F2G Ltd

New P2 trial • Infectious Disease • Respiratory Diseases

Antifungal susceptibility profiles of clinical and environmental Scedosporium and Lomentospora isolates from Taiwan: focus on olorofim activity and phylogenetic heterogeneity. (PubMed, J Antimicrob Chemother) - "Susceptibility in Scedosporium and Lomentospora exhibits high intraspecies variability. Triazoles showed only moderate phylogenetic conservation and cross-resistance, whereas olorofim demonstrated potent, independent activity across all taxa. Given the limited predictive value of species identity, individual susceptibility testing remains essential."

Heterogeneity • Journal • Infectious Disease

Amino acid substitutions at the G118 hotspot in dihydroorotate dehydrogenase confer olorofim resistance in Aspergillus flavus. (PubMed, Microbiol Spectr) - P, P3 | "Importantly, olorofim failed to protect larvae infected with resistant mutants in an infection model. These findings provide essential insights for proactively monitoring and managing olorofim resistance in Aspergillus flavus, aiding clinical and public health responses.This study is registered with ClinicalTrials.gov as NCT05101187 and NCT06969703."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Antifungal exposure in Scedosporium septic arthritis: synovial penetration of voriconazole and terbinafine and plasma concentrations of olorofim. (PubMed, Antimicrob Agents Chemother) - No abstract available

Journal • Immunology • Rheumatology

In Vitro Evaluation of Olorofim and Amphotericin B Combination Therapy Against Talaromyces marneffei. (PubMed, J Fungi (Basel)) - "Combinations of AmB and olorofim were also indifferent in time-kill experiments. Although synergy was not observed, and olorofim is unlikely to enhance AmB induction therapy, olorofim may have a role in the consolidation and maintenance therapy of talaromycosis."

Journal • Preclinical • Infectious Disease

TREATMENT OF PAEDIATRIC LOMENTOSPORA PROLIFICANS INFECTION WITH OLOROFIM: CASE SERIES (ESPID 2026) - "Chemotherapy was ceased and Olorofim (maintenance 30mg bd) was given with voriconazole and terbinafine. The patient received adjunctive immunotherapy (nivolumab and interferon gamma) and hyperbaric oxygen...Conclusions/Learning Points This case series reports clinical use of Olorofim in children with L.prolificans infection, demonstrating success in localised and disseminated disease including immunocompromised and immunocompetent hosts. The findings highlight Olorofim's emerging role in treatment of L.prolificans in children and the need for wider access."

Clinical • Infectious Disease • IFNG

Invasive Fungal Sinusitis in Patients With Hematological Malignancies: A 20-Year Study From a Tertiary Academic US Hospital System. (PubMed, Open Forum Infect Dis) - "Amphotericin B (96.8%) and voriconazole (71.0%) were frequently used, and newer antifungals included isavuconazole (38.7%), olorofim (3.3%), and fosmanogepix (3.3%). Mortality was 22.6% at 1 month, 25.8% at 2 months, 32.3% at 3 months, 41.9% at 6 months, 54.8% at 1 year, 58.1% at 2 years, and 64.5% at 3 years. Despite novel therapies and aggressive surgical interventions, patients with IFS had high mortality."

IO biomarker • Journal • Acute Myelogenous Leukemia • Dermatology • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Otorhinolaryngology • Respiratory Diseases • Sinusitis • FLT3

FIRST REPORTED PAEDIATRIC USE OF OLOROFIM FOR REFRACTORY INVASIVE LOMENTOSPORA PROLIFICANS INFECTION FOLLOWING TRAUMATIC INJURY IN IRELAND (ESPID 2026) - "Despite combination therapy with Liposomal amphotericin B, Voriconazole, Terbinafine, and the novel agent Fosmanogepix, surgical specimens remained persistently culture-positive for Lomentospora prolificans.Given severe life-threatening infection, compassionate-release Olorofim therapy was initiated Learning Points/Discussion Olorofim, the first Orotomide-class antifungal, inhibits fungal dihydroorotate dehydrogenase, an essential enzyme in pyrimidine biosynthesis. This experience supports Olorofim as a promising therapeutic option for invasive mold infections with limited alternatives. To our knowledge, this represents the first reported use of Olorofim in a paediatric patient in Ireland"

Infectious Disease

New Perspectives on Antimicrobial Agents: Fosmanogepix. (PubMed, Antimicrob Agents Chemother) - "Novel first-in-class antifungal agents have been recently approved (ibrexafungerp) or are currently being tested in clinical trials and are available via expanded access programs (olorofim, fosmanogepix). Novel gepix compounds have been developed and could make their niche in the future (e.g., APX2039, prodrug: APX2096, for cryptococcal meningitis, and APX2020, prodrug: APX2097, for coccidioidomycosis). This review discusses the future place of fosmanogepix in the antifungal armamentarium against IFIs."

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

Drug-Induced Liver Injury From a Novel Antifungal - Olorofim. (PubMed, ACG Case Rep J) - "Rechallenge at a reduced dose did not reproduce the transaminase elevations, consistent with a probable Roussel-Uclaf Causality Assessment Method score of 8. Close hepatic monitoring and dose considerations are warranted as olorofim moves toward broader clinical use."

Journal • Hepatology • Liver Failure • Respiratory Diseases

Evaluation of the cytochrome P450-mediated drug interaction profile of olorofim. (PubMed, Antimicrob Agents Chemother) - P1, P2 | "When used with strong CYP3A4 inhibitors, dual moderate inhibitors like fluconazole, or CYP3A4 inducers, dose adjustments were needed for olorofim. Physiologically based PK (PBPK) modeling predicted moderate effects with CYP3A4 inhibitors or inducers and negligible effects with weak CYP3A4 inhibitors or strong inhibitors of CYP2D6, CYP2C8, and CYP2C9. Overall, the drug's interaction profile is predictable and manageable, making it a suitable candidate drug to use in treating patients with invasive fungal disease (IFD), who often require polypharmacy.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT02680808, NCT02730442, NCT02737371, NCT04171739, NCT03340597, and NCT03583164."

Journal • Infectious Disease • CYP1A2 • CYP2C9

A new generation of assays to overcome current limitations of detection of azole resistance in Aspergillus fumigatus. (PubMed, Future Microbiol) - No abstract available

Journal

New antifungals for the treatment of invasive mold disease. (PubMed, Clin Microbiol Infect) - "Development of new antifungal agents is challenging due to limited target sites, emergence of resistance, and adverse toxicity profiles. However, clinical data from fosmanogepix, olorofim, and encochleated amphotericin B are promising in both clinical efficacy and safety for the treatment of invasive mold infections. These new agents offer alternative options for difficult to treat infections, while providing promising efficacy and improved safety outcomes."

Journal • Review • Infectious Disease