P-1351. Fosmanogepix Expanded Access Experience in Patients With Fusarium Infections

TL;DR

Fosmanogepix shows promise as a treatment for difficult-to-treat Fusarium infections in patients with limited options.

Contribution

This study reports real-world clinical outcomes of fosmanogepix in treating Fusarium infections through expanded access.

Findings

Fosmanogepix was well tolerated and showed favorable responses in 76% of hematologic patients and 81% of non-hematologic patients.

Eighty percent of patients in a fungal meningitis outbreak survived after treatment with fosmanogepix.

Fosmanogepix was effective against infections caused by Fusarium solani, which are resistant to other antifungals.

Abstract

Fosmanogepix (FMGX; prodrug, active moiety manogepix [MGX]) is the first member of the “gepix” antifungal class. FMGX inhibits Gwt1, depleting GPI-anchor proteins important for fungal cell wall integrity; it shows consistent in vitro activity against Fusarium spp and wide tissue distribution. FMGX is available via expanded access (EA) for patients with no alternative treatment options (NCT06433128).Table 1.Demographics and Underlying Conditions*Hemophagocytic lymphohistiocytosis; bone marrow failure.†Autosomal-dominant hyper IgE syndrome, chronic sinusitis, corticosteroid use, end-stage renal disease, heart failure, and prosthetic joint infection.Data cutoff date: 01-Mar-2025. Based on unmonitored data derived from forms provided by physicians treating patients with fosmanogepix via expanded access.HSCT, hematopoietic stem cell transplant; IgE, immunoglobulin E.Table 2.Posttraumatic osteomyelitis caused by Fusarium spp*Fracture locations: ankle (2), heel/calcaneus (2), tibia (2), femur (1), humerus (1), toe (1).†Acute kidney injury (4), severe hypokalemia (1).‡Includes hallucinations on voriconazole (1) and transaminase elevations on posaconazole (1).§Includes 6 patients with a global favorable response based on the assessment of the treating physician and 1 patient with reported clinical improvement but no assessment of global response. The response assessment is pending for 1 additional patient. One patient discontinued fosmanogepix treatment on Day 3 due to diarrhea.Data cutoff date: 01-Mar-2025. Based on unmonitored data derived from forms provided by physicians treating patients with fosmanogepix via expanded access.

Demographics and Underlying Conditions

*Hemophagocytic lymphohistiocytosis; bone marrow failure.

†Autosomal-dominant hyper IgE syndrome, chronic sinusitis, corticosteroid use, end-stage renal disease, heart failure, and prosthetic joint infection.

Data cutoff date: 01-Mar-2025. Based on unmonitored data derived from forms provided by physicians treating patients with fosmanogepix via expanded access.

HSCT, hematopoietic stem cell transplant; IgE, immunoglobulin E.

Posttraumatic osteomyelitis caused by Fusarium spp

*Fracture locations: ankle (2), heel/calcaneus (2), tibia (2), femur (1), humerus (1), toe (1).

†Acute kidney injury (4), severe hypokalemia (1).

‡Includes hallucinations on voriconazole (1) and transaminase elevations on posaconazole (1).

§Includes 6 patients with a global favorable response based on the assessment of the treating physician and 1 patient with reported clinical improvement but no assessment of global response. The response assessment is pending for 1 additional patient. One patient discontinued fosmanogepix treatment on Day 3 due to diarrhea.

Data cutoff date: 01-Mar-2025. Based on unmonitored data derived from forms provided by physicians treating patients with fosmanogepix via expanded access.

Patients with documented Fusarium infections received FMGX via EA. Data including global response (clinical, radiological, mycological) were collected using structured forms.Figure 1.Response to fosmanogepix treatment in patients with (A) hematologic and (B) non-hematologic conditions*Global response assessed by treating physician, evaluated as a composite of clinical, radiological and mycological response.†Global response assessment by treating physician pending.

Response to fosmanogepix treatment in patients with (A) hematologic and (B) non-hematologic conditions

*Global response assessed by treating physician, evaluated as a composite of clinical, radiological and mycological response.

†Global response assessment by treating physician pending.

92 patients (34 females; median age 50.5 [range, 10–83] y) from 7 countries (92% US) completed FMGX treatment. Fusarium solani was most common, with high MICs for triazoles and/or amphotericin B and low MICs for MGX.

10 previously healthy people (9 female, median age 30.5 y) from the US (8) and Mexico (2) received FMGX during a fungal meningitis outbreak from iatrogenic contamination (epidural anesthesia), with 80% survival.

50 patients had hematologic conditions, mainly acute leukemia (Table 1; 21 [42%] disseminated infections, 22 bloodstream, 38 skin involvement). Response was favorable in 38 patients (76%; Fig 1A); 16 patients (32%) died (9) or transferred to hospice care (7) ≤ 6 weeks after starting FMGX. FMGX was well tolerated up to 609 (median 88.5) days.

32 patients had nonhematologic conditions (trauma [14], solid organ transplant [5], diabetes [5]; Table 1). Most infections were osteoarticular (12) and/or of skin/soft tissue (8). Overall clinical response was favorable in 26 patients (81%; Fig 1B), including 7/9 with posttraumatic osteomyelitis (OM; Table 2). No patient died ≤ 6 weeks after starting FMGX. FMGX was well tolerated up to 417 (median 69) days.

Most common adverse reactions with FMGX were gastrointestinal (eg, nausea, vomiting, diarrhea), leading to discontinuation in 3 patients.

Based on this large prospective assessment in an EA setting, FMGX provides a potentially life-saving treatment option in difficult-to-treat Fusarium infections in diverse patient scenarios, including hematologic malignancies, outbreak-associated meningitis, and posttraumatic OM, and was well tolerated for long treatment durations.

Sanjeet S. Dadwal, MD, Ansun Biopharma: Grant/Research Support|Aseptiscope, Inc.: Stocks/Bonds (Private Company)|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|F2G: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|Karius: Honoraria|Merck: Advisor/Consultant|Pfizer: Grant/Research Support|Pulmotect: Grant/Research Support|Symbio: Grant/Research Support|Takeda: Advisor/Consultant M Hong Nguyen, MD, Basilea: Advisor/Consultant|BioMerieux: Grant/Research Support|Melinta: Grant/Research Support|Pulmocide: Advisor/Consultant|Pulmocide: Grant/Research Support Jannik Stemler, MD, AbbVie: Honoraria|Akademie für Infektionsmedizin: Honoraria|Alvea Vax: Advisor/Consultant|Basilea: Grant/Research Support|German Federal Ministry of Education and Research (BMBF): Grant/Research Support|German Society for Infectious Diseases: Travel grants|Gilead: Advisor/Consultant|Gilead: Honoraria|Hikma: Honoraria|Lilly: Honoraria|Meta-Alexander Foundation: Travel grants|Micron Research: Advisor/Consultant|Mundipharma: Honoraria|Noscendo: Grant/Research Support|Pfizer: Honoraria|Scynexis: Grant/Research Support|The Medical Faculty of the University of Cologne: Grant/Research Support Haran Schlamm, MD, Amplyx: Advisor/Consultant|Basilea: Advisor/Consultant|Pfizer: Advisor/Consultant Luis Ostrosky-Zeichner, MD, Basilea: Advisor/Consultant|Basilea: Grant/Research Support|Basilea: Honoraria|Eurofins Viracor: Advisor/Consultant|Eurofins Viracor: Grant/Research Support|Eurofins Viracor: Honoraria|F2G: Advisor/Consultant|F2G: Grant/Research Support|F2G: Honoraria|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|GSK: Advisor/Consultant|GSK: Grant/Research Support|GSK: Honoraria|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Melinta: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Pulmocide: Advisor/Consultant|Pulmocide: Grant/Research Support|Pulmocide: Honoraria|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support|Scynexis: Honoraria|T2 Biosystems: Advisor/Consultant|T2 Biosystems: Grant/Research Support|T2 Biosystems: Honoraria

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