Olorofim (orotomide) / F2G, Shionogi - LARVOL DELTA

Antifungal treatment strategies in intensive care unit patients. (PubMed, Eur J Clin Invest) - "Optimizing antifungal stewardship through individualized therapy and early diagnosis remains essential to improve outcomes in this high-risk population."

Journal • Review • Candidiasis • Critical care • Human Immunodeficiency Virus • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

Invasive Pulmonary Aspergillosis in Non-Neutropenic Patients: An Evolving Clinical Paradigm. (PubMed, Diagnostics (Basel)) - "Voriconazole remains the first-line treatment, though therapeutic drug monitoring is essential to ensure efficacy and minimize toxicity. Isavuconazole represents an effective alternative, offering comparable efficacy, improved safety, predictable pharmacokinetics, and convenient once-daily dosing. Liposomal amphotericin B serves as a valuable option in severe or refractory cases due to its broad-spectrum activity and reduced nephrotoxicity...Emerging antifungal agents, including olorofim, ibrexafungerp, and fosmanogepix, show promise against resistant Aspergillus species, expanding treatment options. Overall, IPA management in non-neutropenic patients requires a multidisciplinary, patient-centered approach integrating established antifungals, supportive care, and novel therapeutic advances."

Journal • Review • Hematological Disorders • Infectious Disease • Neutropenia • Pulmonary Disease • Respiratory Diseases

Compassionate Use of Olorofim for Invasive Mold Infections: A Nationwide Observational Study in France. (PubMed, Open Forum Infect Dis) - "Olorofim exhibited potential efficacy and good tolerability in patients with refractory IMIs. Further data from ongoing clinical trials are needed to confirm these findings."

Journal • Observational data • Immunology • Infectious Disease • Primary Immunodeficiency • Pulmonary Disease • Respiratory Diseases • Transplantation

Beyond Fumigatus: a molecular portrait of clinical Aspergillus diversity, pathogenicity, and antifungal resistance. (PubMed, Antimicrob Agents Chemother) - "Antifungal susceptibility testing showed that olorofim had the lowest minimal inhibitory concentrations across species...This study presents one of the largest species-level data sets of Aspergillus isolates to date, underscoring the diversity, pathogenic potential, and resistance profiles of non-fumigatus species. Accurate species identification plays an important role in guiding appropriate antifungal therapy and improving clinical outcomes, although further studies are needed to elucidate its direct impact on treatment decisions."

Journal • Bronchiectasis • Genetic Disorders • Immunology • Infectious Disease • Nontuberculous Mycobacterial Disease • Primary Immunodeficiency • Pulmonary Disease • Respiratory Diseases • RAG1

OASIS: Olorofim Aspergillus Infection Study (clinicaltrials.gov) - P3 | N=225 | Active, not recruiting | Sponsor: F2G Biotech GmbH | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Paradoxical worsening on olorofim in patients undergoing treatment for invasive fungal diseases. (PubMed, Clin Microbiol Infect) - P2 | "Paradoxical reactions to appropriate antimicrobial therapy are infrequently observed in systemic fungal diseases. Similar responses are seen in the treatment of both tuberculosis (TB) (worsening of lymphadenitis) and leprosy (reversal reactions) suggesting a similar pathophysiologic mechanism may be responsible given the overlapping immune response between mycobacterial and fungal pathogens. Awareness of this potential syndrome is essential during the treatment of patients with olorofim therapy."

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

Non-Aspergillus molds. (PubMed, JHLT Open) - "In general, lipid preparations of amphotericin B or azole antifungals (voriconazole, posaconazole, isavuconazole) are frequently used for treatment. Investigational therapies such as fosmanogepix or olorofim are promising as future treatment modalities for some of these difficult-to-treat non-Aspergillus molds."

Journal • Review • Cardiovascular • Hematological Disorders • Infectious Disease • Neutropenia • Respiratory Diseases • Thrombosis • Transplantation

Evidence Based Approach of Antifungal Prophylaxis (AFP) in Hematological Malignancies (DGHO 2025) - "Ten trials with HMA monotherapy (n=1,185), 10 with HMA/venetoclax (n=956) and 4 with FLT3-inhibitors (n=273) were analyzed...No prospective RT for AFP with isavuconazole, rezafungin or olorofim are available.In pts receiving HMA therapy, IFI ranged between 1.6 and 10.3% while AFP was usually not given...In pts treated with midostaurin, two studies (n= 218 pts) reported 29 IFI (13.3%). A total of 20,753 AFP pts episodes (eps) were included since 1984 from 95 studies during CTx and 17,482 pts received AFP within a clinical trial for AFP from 1992 to 2022. Out of these, 7,586 received fluconazole (FLU), 4,080 were on trials with posaconazole (POS) or voriconazole (VOR), 1,717 received itraconazole (ITRA), 1,895 echinocandins and 1,594 amphotericin B (AmB)(AmB deoxycholate, liposomal AmB or inhalative AmB), respectively. In pts receiving novel targeted therapies (e.g."

Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology

40 Years of Preventing Fungal Infections in Hematological Malignancies - Lessons Learned from Clinical Trials with 20,753 Patients (ASH 2024) - "Out of these, 7,586 received fluconazole (FLU), 4,080 were included in trials with posaconazole (POS) or voriconazole (VOR), 1,717 received itraconazole (ITRA), 1,895 echinocandins and 1,594 amphotericin B (AmB)(AmB deoxycholate, liposomal AmB or inhalational AmB), respectively...No prospective studies for AFP with isavuconazole and new antifungal agents like rezafungin or olorofim are available...In those receiving venetoclax/HMA, AFP practices were heterogeneous and IFI incidence ranged from 5% to 16.1% (overall probable/proven IFI : n=102 (10.6%), possible IFI not reported in all studies). In pts treated with midostaurin, 2 studies (n= 218 pts) reported 29 probable/proven IFI (13.3%). In pts treated with gilteritinib, 2 studies reported 55 pts with an IFI rate of 27.2% (including possible IFI)...Despite numerous trials for prevention of IFI, only posaconazole and fluconazole proved reduction in OM rates. There is a need for prospective clinical trials addressing..."

Clinical • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology

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

Antagonistic in vitro interaction between olorofim and voriconazole against Aspergillus fumigatus. (PubMed, J Antimicrob Chemother) - "These findings demonstrate the in vitro antagonism between olorofim and voriconazole and underscore the need for further investigation before considering their combined clinical use."

Journal • Preclinical

Olorofim, a potential novel drug candidate against Helicobacter pylori infection. (PubMed, J Antibiot (Tokyo)) - "Olorofim demonstrated a strong bactericidal effect against H. pylori, making it a promising drug candidate for treating antibiotic-resistant cases. However, both our experimental findings and sequence analysis suggest that the DHODH enzyme in H. pylori is unlikely to be the molecular target of this drug candidate."

Journal • Gastric Cancer • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Oncology • Peptic Ulcer • Solid Tumor

Antifungal treatment strategies and their impact on resistance development in clinical settings. (PubMed, J Antimicrob Chemother) - "New antifungal agents, such as rezafungin, olorofim and fosmanogepix, along with long-acting and advanced formulations plus combination regimens, show substantial promise for managing resistance and improving treatment outcomes. Addressing antifungal resistance demands a multifaceted 'One Health' approach that integrates robust diagnostics, antifungal stewardship (AFS), precision medicine and collaborative global efforts. By advancing drug formulations, enhancing diagnostic tools and implementing forward-thinking AFS practices, the healthcare community can better tackle the escalating burden of fungal infections and deliver improved patient outcomes."

IO biomarker • Journal • Infectious Disease

In vitro evaluation of olorofim and antifungal combinations against Aspergillus and Candida species. (PubMed, J Antimicrob Chemother) - "Mould-active azoles antagonize olorofim activity against Aspergillus spp. combination MICs remain within wild-type distributions for Aspergillus spp., other than for A. niger. In addition, olorofim does not affect the anti-Candida effect of fluconazole and could be co-dosed where necessary without loss of the effect of the azole against the yeast."

Journal • Preclinical • Infectious Disease

Olorofim activity against multidrug-resistant Fusarium unveils intra-species and inter-species variability. (PubMed, Antimicrob Agents Chemother) - "Clinical isolates tended to have higher MIC values than environmental isolates, but this pattern was not consistent across all species complexes. Overall, olorofim demonstrated moderate in vitro activity against Fusarium isolates, suggesting it might be a potential candidate for treating fusarioses caused by multidrug-resistant strains."

Journal • Immunology • 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

Endocarditis caused by Scopulariopsis brevicaulis with disseminated emboli and multiple vascular aneurysms: A case report and literature review. (PubMed, IDCases) - "Determining minimum inhibitory concentrations (MICs) is essential for guiding treatment decisions, even in the absence of established clinical breakpoints for this pathogen. Olorofilm, a novel oral antifungal, demonstrates remarkable potential for treating S. brevicaulis."

Journal • Cardiovascular • Infectious Disease

Case Commentary: Successful use of olorofim for the treatment of multi-drug-resistant Lomentospora prolificans infection in a child. (PubMed, Antimicrob Agents Chemother) - "The case presented by Fortini et al. (Antimicrob Agents Chemother 69:e00602-25, 2025, https://doi.org/10.1128/aac.00602-25) describes the successful use of olorofim treatment in an 8-year-old who suffered from Lomentospora prolificans tendonitis, synovitis, and osteomyelitis."

Journal • Infectious Disease • Inflammation

Antagonistic interaction between posaconazole and olorofim in a murine model of invasive pulmonary aspergillosis. (PubMed, J Antimicrob Chemother) - "Posaconazole reduces the effect of olorofim in vivo. A combination of olorofim and a mould-active triazole is likely efficacious in wild-type infections but may be suboptimal in triazole resistance infections where there is minimal contribution of the mould-active triazole to antifungal activity and the triazole antagonises olorofim to produce a submaximal effect."

Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Olorofim for the treatment of Central Nervous System (CNS) invasive fungal infections (IFI) in patients with limited or no treatment options: a sub-analysis of an open-label, single-arm, Phase 2b trial (Study 32; NCT03583164) (IDWeek 2025) - P2 | No abstract available

Clinical • P2b data • Infectious Disease

Olorofim for the treatment of Central Nervous System (CNS) invasive fungal infections (IFI) in patients with limited or no treatment options: a sub-analysis of an open-label, single-arm, Phase 2b trial (Study 32; NCT03583164) (IDWeek 2025) - P2 | No abstract available

Clinical • P2b data • 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

Successful use of olorofim for the treatment of Lomentospora prolificans knee tendonitis, synovitis, and concomitant osteomyelitis in an immunocompetent child. (PubMed, Antimicrob Agents Chemother) - "This pathogen is challenging to treat due to its high MICs to available antifungals. We present a case of an 8-year-old previously healthy female who developed L. prolificans knee tendonitis and synovitis with patellar osteomyelitis after a flat patio stone laceration in Southern California, who ultimately was treated with the novel antifungal, olorofim."

Journal • Infectious Disease • Inflammation

Cost-effectiveness of olorofim in the treatment of invasive aspergillosis in patients with limited suitable alternative treatment options: a US payer perspective. (PubMed, Antimicrob Agents Chemother) - P2 | "Upon probabilistic sensitivity analysis, olorofim was dominant in 90.0% of 1,000 iterations and cost-effective in 97.5%. Olorofim resulted in lower total treatment costs, antifungal costs, and more QALY gains versus currently available salvage therapy, making olorofim the dominant strategy for treating IA with limited treatment options."

HEOR • Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Spectrum of clinically significant melanized fungi in NIH hospitalized patients and their antifungal susceptibility profiles. (PubMed, Med Mycol) - "Antifungal susceptibility testing against eight antifungal agents showed that azoles, micafungin, and terbinafine exhibited in vitro activity against most isolates. In contrast, olorofim, and amphotericin B were less effective. Notably, Phaeoacremonium species (Calosphaeriales) exhibited distinct antifungal susceptibility patterns. Accurate identification of melanized fungi in clinical laboratories is essential for selecting effective antifungal therapy, understanding susceptibility patterns to available agents, supporting epidemiological monitoring, and ultimately enhancing clinical outcomes in patients affected by these often complex and opportunistic infections."

Journal • Infectious Disease