{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:51:52Z","timestamp":1791219112545,"version":"4.1.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017467","name":"Amplyx Pharmaceuticals, Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017467","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Fosmanogepix (APX001), a first-in-class, intravenous (IV) and oral (PO) antifungal prodrug, is being developed to treat invasive fungal diseases (IFDs). Manogepix (APX001A; active moiety) targets fungal glycosylphosphatidylinositol-anchored cell wall transfer protein 1, inhibiting cell wall synthesis causing loss of viability. This open-label, multicentre, Phase 1b study in patients with AML and neutropenia (absolute neutrophil count &amp;lt;500 cells\/\u03bcL; &amp;gt;10 days) undergoing chemotherapy aimed to assess tolerability, safety and pharmacokinetics (PK) of IV and PO fosmanogepix.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Of 21 adult AML patients undergoing remission induction chemotherapy, 10 received IV fosmanogepix (600 mg; q24h) and 11 received oral fosmanogepix (500 mg; q24h) over 14 days, with a 28 day follow-up. Patients also received remission induction chemotherapy [sequential high-dose cytarabine and mitoxantrone (S-HAM) or 7\u200a+\u200a3 regimen] for AML and IFD prophylaxis (posaconazole). A two-compartmental PK model from previous studies in healthy volunteers was fitted to manogepix plasma data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 26 fosmanogepix-related adverse events (AEs; IV: 14; PO: 12) in 9 (42.9%) patients [IV: 5 (50%); PO: 4 (36.4%)], none were serious or resulted in fosmanogepix discontinuation. Most frequently occurring fosmanogepix-related AEs were Grade 1\/2 nausea [four events in three patients (14.3%)]; vomiting, ALT increase, and delirium [two events; two patients (9.5%) each]. One patient experienced fosmanogepix-related Grade 3 hypertension. Dose-corrected geometric mean ratio of AUC (PO-to-IV) was 95%. Elimination half-lives (\u223c2 days) were consistent with prior studies in healthy volunteers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Fosmanogepix was safe and well tolerated in AML patients with neutropenia receiving remission induction chemotherapy. Safety and PK profiles were comparable to healthy volunteers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkad269","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T14:28:32Z","timestamp":1692800912000},"page":"2645-2652","source":"Crossref","is-referenced-by-count":20,"title":["Phase 1b safety and pharmacokinetics of intravenous and oral fosmanogepix in patients with acute myeloid leukaemia and neutropenia"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9599-3137","authenticated-orcid":false,"given":"Oliver A","family":"Cornely","sequence":"first","affiliation":[{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne , Cologne , Germany"},{"name":"University Hospital of Cologne, Department of Internal Medicine, Medical Faculty, University Hospital of Cologne , Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Ostermann","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Ludwig Maximilian University of Munich , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Koehler","sequence":"additional","affiliation":[{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne , Cologne , Germany"},{"name":"University Hospital of Cologne, Department of Internal Medicine, Medical Faculty, University Hospital of Cologne , Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Teschner","sequence":"additional","affiliation":[{"name":"University Medical Center of the Johannes Gutenberg University Mainz, Department of Hematology, and Medical Oncology , Mainz , Germany"},{"name":"Department of Internal Medicine II, University Hospital W\u00fcrzburg , W\u00fcrzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Endrik","family":"Limburg","sequence":"additional","affiliation":[{"name":"Clinical Trials Centre Cologne (CTCC), University of Cologne , Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G","family":"Kramer","sequence":"additional","affiliation":[{"name":"Kramer Consulting LLC , North Potomac, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara H","family":"Barbat","sequence":"additional","affiliation":[{"name":"Amplyx Pharmaceuticals Inc. , San Diego, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6815-2647","authenticated-orcid":false,"given":"Margaret","family":"Tawadrous","sequence":"additional","affiliation":[{"name":"Pfizer Inc. , 445 Eastern Point Road, Groton, CT 06340 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"Hodges","sequence":"additional","affiliation":[{"name":"Amplyx Pharmaceuticals Inc. , San Diego, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,8]]},"reference":[{"key":"2023110823044687700_dkad269-B1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3390\/jof3040057","article-title":"Global and multi-national prevalence of fungal diseases-estimate precision","volume":"3","author":"Bongomin","year":"2017","journal-title":"J Fungi (Basel)"},{"key":"2023110823044687700_dkad269-B2","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofab593","article-title":"Prevalence and healthcare burden of fungal infections in the United States, 2018","volume":"9","author":"Rayens","year":"2022","journal-title":"Open Forum Infect Dis"},{"key":"2023110823044687700_dkad269-B3","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.3389\/fmicb.2015.01322","article-title":"Optimizing outcomes in immunocompromised hosts: understanding the role of immunotherapy in invasive fungal diseases","volume":"6","author":"Ravikumar","year":"2015","journal-title":"Front Microbiol"},{"key":"2023110823044687700_dkad269-B4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0176576","article-title":"Candidemia in the elderly: what does it change?","volume":"12","author":"Barchiesi","year":"2017","journal-title":"PLoS One"},{"key":"2023110823044687700_dkad269-B5","doi-asserted-by":"crossref","first-page":"e375","DOI":"10.1016\/S1473-3099(21)00203-6","article-title":"Global guideline for the diagnosis and management of rare yeast infections: an initiative of the ECMM in cooperation with ISHAM and ASM","volume":"21","author":"Chen","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"2023110823044687700_dkad269-B6","doi-asserted-by":"crossref","first-page":"e246","DOI":"10.1016\/S1473-3099(20)30784-2","article-title":"Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology","volume":"21","author":"Hoenigl","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"2023110823044687700_dkad269-B7","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41579-022-00720-1","article-title":"Tackling the emerging threat of antifungal resistance to human health","volume":"20","author":"Fisher","year":"2022","journal-title":"Nat Rev Microbiol"},{"key":"2023110823044687700_dkad269-B8","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1111\/jcpt.13352","article-title":"Influence of switching from intravenous to oral administration on serum voriconazole concentration","volume":"46","author":"Harada","year":"2021","journal-title":"J Clin Pharm Ther"},{"key":"2023110823044687700_dkad269-B9","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s11046-021-00560-2","article-title":"Advances in anti-fungal therapies","volume":"186","author":"Waterer","year":"2021","journal-title":"Mycopathologia"},{"key":"2023110823044687700_dkad269-B10","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.12659\/MSM.893142","article-title":"Clinical analysis of adverse drug reactions between vincristine and triazoles in children with acute lymphoblastic leukemia","volume":"21","author":"Yang","year":"2015","journal-title":"Med Sci Monit"},{"key":"2023110823044687700_dkad269-B11","doi-asserted-by":"crossref","first-page":"877","DOI":"10.3390\/antibiotics9120877","article-title":"Drug-resistant fungi: an emerging challenge threatening our limited antifungal armamentarium","volume":"9","author":"Arastehfar","year":"2020","journal-title":"Antibiotics (Basel)"},{"key":"2023110823044687700_dkad269-B12","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1007\/s40265-021-01611-0","article-title":"The antifungal pipeline: fosmanogepix, ibrexafungerp, olorofim, opelconazole, and rezafungin","volume":"81","author":"Hoenigl","year":"2021","journal-title":"Drugs"},{"key":"2023110823044687700_dkad269-B13","doi-asserted-by":"crossref","first-page":"239","DOI":"10.3390\/jof6040239","article-title":"Fosmanogepix: a review of the first-in-class broad spectrum agent for the treatment of invasive fungal infections","volume":"6","author":"Shaw","year":"2020","journal-title":"J Fungi (Basel)"},{"key":"2023110823044687700_dkad269-B14","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2021.759408","article-title":"Drug resistance and novel therapeutic approaches in invasive candidiasis","volume":"11","author":"Murphy","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"2023110823044687700_dkad269-B15","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02476-20","article-title":"Therapeutic potential of fosmanogepix (APX001) for intra-abdominal candidiasis: from lesion penetration to efficacy in a mouse model","volume":"65","author":"Lee","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2023110823044687700_dkad269-B16","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01795-20","article-title":"Efficacy and pharmacokinetics of fosmanogepix (APX001) in the treatment of Candida endophthalmitis and hematogenous meningoencephalitis in nonneutropenic rabbits","volume":"65","author":"Petraitiene","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2023110823044687700_dkad269-B17","article-title":"In Vitro Activity of E1210 and In Vivo Activity of E1211, a Water-Soluble Prodrug of E1210, in Combination with Other Antifungals","author":"Watanabe","year":"2014"},{"key":"2023110823044687700_dkad269-B18","doi-asserted-by":"crossref","DOI":"10.1128\/aac.01419-22","article-title":"Clinical efficacy and safety of a novel antifungal, fosmanogepix, in patients with candidemia caused by Candida auris: results from a Phase 2 trial","volume":"67","author":"Vazquez","year":"2023","journal-title":"Antimicrob Agents Chemother"},{"key":"2023110823044687700_dkad269-B19","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02343-20","article-title":"Manogepix, the active moiety of the investigational agent fosmanogepix, demonstrates in vitro activity against members of the Fusarium oxysporum and Fusarium solani species complexes","volume":"65","author":"Badali","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2023110823044687700_dkad269-B20","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01120-19","article-title":"Efficacy of delayed therapy with fosmanogepix (APX001) in a murine model of Candida auris invasive candidiasis","volume":"63","author":"Wiederhold","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2023110823044687700_dkad269-B21","doi-asserted-by":"crossref","DOI":"10.1128\/aac.01623-22","article-title":"Safety and pharmacokinetics of intravenous and oral fosmanogepix, a first-in-class antifungal agent, in healthy volunteers","volume":"67","author":"Hodges","year":"2023","journal-title":"Antimicrob Agents Chemother"},{"key":"2023110823044687700_dkad269-B22","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1080\/17512433.2021.1949285","article-title":"Recent advances and future perspectives in the pharmacological treatment of Candida auris infections","volume":"14","author":"Giacobbe","year":"2021","journal-title":"Expert Rev Clin Pharmacol"},{"key":"2023110823044687700_dkad269-B23","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1080\/13543784.2022.2086120","article-title":"Invasive candidiasis: investigational drugs in the clinical development pipeline and mechanisms of action","volume":"31","author":"Hoenigl","year":"2022","journal-title":"Expert Opin Investig Drugs"},{"issue":"Suppl 1","key":"2023110823044687700_dkad269-B24","doi-asserted-by":"crossref","first-page":"S526","DOI":"10.1093\/ofid\/ofx163.1370","article-title":"First-in-human study to assess safety, tolerability and pharmacokinetics of APX001 administered by intravenous infusion to healthy subjects","volume":"4","author":"Hodges","year":"2017","journal-title":"Open Forum Infect Dis"},{"issue":"Suppl 1","key":"2023110823044687700_dkad269-B25","doi-asserted-by":"crossref","first-page":"S534","DOI":"10.1093\/ofid\/ofx163.1390","article-title":"Phase 1 study to assess safety, tolerability and pharmacokinetics of single and multiple oral doses of APX001 and to investigate the effect of food on APX001 bioavailability","volume":"4","author":"Hodges","year":"2017","journal-title":"Open Forum Infect Dis"},{"key":"2023110823044687700_dkad269-B26","doi-asserted-by":"crossref","first-page":"100278","DOI":"10.1016\/j.ctarc.2020.100278","article-title":"Chemotherapy-induced nausea and vomiting: pathogenesis, recommendations, and new trends","volume":"26","author":"Gupta","year":"2021","journal-title":"Cancer Treat Res Commun"},{"key":"2023110823044687700_dkad269-B27","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1086\/598327","article-title":"Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents","volume":"48","author":"Br\u00fcggemann","year":"2009","journal-title":"Clin Infect Dis"},{"key":"2023110823044687700_dkad269-B28","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1055\/s-0039-3400291","article-title":"Antifungal therapy: new and evolving therapies","volume":"41","author":"Nivoix","year":"2020","journal-title":"Semin Respir Crit Care Med"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/11\/2645\/52814524\/dkad269.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/11\/2645\/52814524\/dkad269.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T18:05:22Z","timestamp":1699466722000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/78\/11\/2645\/7264060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,8]]},"references-count":28,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,9,8]]},"published-print":{"date-parts":[[2023,11,6]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkad269","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,11]]},"published":{"date-parts":[[2023,9,8]]}}}