Olorofim (orotomide) / Shionogi 
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  • ||||||||||  Olorofim (orotomide) / F2G
    Journal:  Pandemic Response Box® library as a source of antifungal drugs against Scedosporium and Lomentospora species. (Pubmed Central) -  Feb 4, 2023   
    Reactive oxygen species production, mitochondrial activity and surface components were analyzed by fluorescent probes when S. aurantiacum was treated with selected drugs and revealed that some cell parameters are altered by these compounds. In conclusion, alexidine, amorolfine and olorofim were identified as promising compounds to be studied against scedosporiosis and lomentosporiosis.
  • ||||||||||  Olorofim (orotomide) / F2G
    Preclinical, Journal:  In Vitro Activity of the Novel Antifungal Olorofim against Scedosporium and Lomentospora prolificans. (Pubmed Central) -  Jan 12, 2023   
    The manuscript contributes to our knowledge of the activity of the new antifungal agent olorofim and comparator agents against Lomentospora and against Scedosporium isolates that have been molecularly identified to the species level. The efficacy of olorofim against all species of Scedosporium and Lomentospora was confirmed.
  • ||||||||||  rezafungin IV (CD101 IV) / Cidara Therap, Mundipharma, Melinta Therap, Olorofim (orotomide) / F2G
    Review, Journal:  Acute Lymphoblastic Leukemia and Invasive Mold Infections: A Challenging Field. (Pubmed Central) -  Nov 16, 2022   
    However, their use in ALL patients needs to be investigated through more clinical trials. In summary, this review outlines the epidemiology of IMI and the use of antifungal prophylaxis in ALL patients.
  • ||||||||||  Review, Journal:  Recent Antifungal Pipeline Developments against Candida auris: A Systematic Review. (Pubmed Central) -  Nov 16, 2022   
    All these compounds demonstrated significant improvements in survival and reduction in tissue fungal burden on neutropenic animal models of candidemia due to C. auris. Continual efforts towards the discovery of new treatments against this multidrug-resistant fungus are essential.
  • ||||||||||  Clinical, Journal:  Investigational antifungal agents for invasive mycoses: a clinical perspective. (Pubmed Central) -  Sep 3, 2022   
    Although critical information regarding the performance of these agents in heavily immunosuppressed patients is pending, they may provide useful additions to current therapies in some clinical scenarios, including IFI caused by azole-resistant Aspergillus or multi-resistant fungal pathogens (e.g. Candida auris, Lomentospora prolificans). However, their limited activity against Mucorales and some other opportunistic molds (e.g. some Fusarium spp.) persists as a major unmet need.
  • ||||||||||  PK/PD data, Review, Journal:  Pharmacodynamics, Mechanisms of Action and Resistance, and Spectrum of Activity of New Antifungal Agents. (Pubmed Central) -  Aug 27, 2022   
    Others include new agents within established classes or with mechanisms of action similar to clinically available antifungals (ibrexafungerp, rezafungin, oteseconazole, opelconazole, MAT2203) that have been modified in order to improve certain characteristics, including enhanced pharmacokinetics and greater specificity for fungal targets...The tolerability and drug-drug interaction profiles of these new agents also appear to be promising, although the number of human subjects that have been exposed to many of these agents remains relatively small. Overall, these agents have the potential for expanding our antifungal armamentarium and improving clinical outcomes in patients with invasive mycoses.
  • ||||||||||  Olorofim (orotomide) / Shionogi
    Enrollment open, Trial initiation date:  OASIS: Olorofim Aspergillus Infection Study (clinicaltrials.gov) -  Aug 11, 2022   
    P3,  N=225, Recruiting, 
    Overall, these agents have the potential for expanding our antifungal armamentarium and improving clinical outcomes in patients with invasive mycoses. Not yet recruiting --> Recruiting | Initiation date: Nov 2021 --> Mar 2022
  • ||||||||||  Olorofim (orotomide) / F2G
    Trial completion date, Trial primary completion date:  A Phase I Study to Assess the Pharmacokinetics of Olorofim in Subjects With Renal Impairment (clinicaltrials.gov) -  Aug 3, 2022   
    P1,  N=16, Recruiting, 
    Not yet recruiting --> Recruiting | Initiation date: Nov 2021 --> Mar 2022 Trial completion date: Mar 2022 --> Oct 2022 | Trial primary completion date: Mar 2022 --> Oct 2022
  • ||||||||||  Review, Journal:  Antifungal Resistance and the Role of New Therapeutic Agents. (Pubmed Central) -  Jul 13, 2022   
    Isavuconazole and ibrexafungerp represent the two newest antifungal agents...Its utility in treating voriconazole-resistant Candida should be confirmed with susceptibility testing if available...Multiple antifungals, some with novel mechanisms, are in development, including rezafungin, oteseconazole, olorofim, fosmanogepix, and opelconazole...Such an array of antifungals will be important as antifungal resistance continues to expand alongside evolving medical practices. However, managing resistant fungal infections will grow in complexity as the unique role of each new agent is defined.
  • ||||||||||  Olorofim (orotomide) / F2G
    Review, Journal:  Novel Promising Antifungal Target Proteins for Conquering Invasive Fungal Infections. (Pubmed Central) -  Jul 6, 2022   
    Olorofim, as an inhibitor of dihydrolactate dehydrogenase, is a breakthrough drug treatment for IFIs. These novel target proteins and their inhibitors may overcome the limitations of currently available antifungal drugs and improve patient outcomes in the treatment of IFIs.
  • ||||||||||  Review, Journal:  Novel antifungal agents in clinical trials. (Pubmed Central) -  Apr 9, 2022   
    Invasive fungal diseases due to resistant yeasts and molds are an important and increasing public health threat, likely due to a growing population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics.  The significant morbidity and mortality associated with these pathogens bespeaks the urgent need for novel safe and effective therapeutics.  This review highlights promising investigational antifungal agents in clinical phases of development: fosmanogepix, ibrexafungerp, rezafungin, encochleated amphotericin B, oteseconazole (VT-1161), VT-1598, PC945, and olorofim.  We examine three first-in-class members of three novel antifungal classes, as well as new agents within existing antifungal classes with improved safety and tolerability profiles due to enhanced pharmacokinetic and pharmacodynamic properties.
  • ||||||||||  Olorofim (orotomide) / F2G
    Enrollment open:  A Phase I Study to Assess the Pharmacokinetics of Olorofim in Subjects With Renal Impairment (clinicaltrials.gov) -  Mar 31, 2022   
    P1,  N=16, Recruiting, 
     The significant morbidity and mortality associated with these pathogens bespeaks the urgent need for novel safe and effective therapeutics.  This review highlights promising investigational antifungal agents in clinical phases of development: fosmanogepix, ibrexafungerp, rezafungin, encochleated amphotericin B, oteseconazole (VT-1161), VT-1598, PC945, and olorofim.  We examine three first-in-class members of three novel antifungal classes, as well as new agents within existing antifungal classes with improved safety and tolerability profiles due to enhanced pharmacokinetic and pharmacodynamic properties. Not yet recruiting --> Recruiting
  • ||||||||||  Olorofim (orotomide) / F2G
    Preclinical, Journal:  Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma. (Pubmed Central) -  Feb 26, 2022   
    The current antifungal agents used to treat eumycetoma are itraconazole or terbinafine, however, their cure rates are low...They are the benzimidazole carbamates fenbendazole and carbendazim, the 8-aminoquinolone derivative tafenoquine and MMV1578570...Compounds showing potent activity in vitro were further tested in vivo. Fenbendazole, MMV1782387, ravuconazole and olorofim were able to significantly prolong Galleria mellonella larvae survival and are promising candidates to explore in mycetoma treatment and to also serve as scaffolds for medicinal chemistry optimisation in the search for novel antifungals to treat eumycetoma.