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Clinical Trial
. 2025 Dec 24;81(5):e302-e309.
doi: 10.1093/cid/ciaf185.

Fosmanogepix for the Treatment of Invasive Mold Diseases Caused by Aspergillus Species and Rare Molds: A Phase 2, Open-Label Study (AEGIS)

Michael R Hodges  1   2 , Margaret Tawadrous  3 , Oliver A Cornely  4   5   6 , George R Thompson  7 , Monica A Slavin  8 , Johan A Maertens  9   10 , Sanjeet S Dadwal  11 , Galia Rahav  12 , Susan Hazel  13   14 , Mary Almas  15 , Abhijeet Jakate  16 , Rienk Pypstra  3
Affiliations
Clinical Trial

Fosmanogepix for the Treatment of Invasive Mold Diseases Caused by Aspergillus Species and Rare Molds: A Phase 2, Open-Label Study (AEGIS)

Michael R Hodges et al. Clin Infect Dis. .

Abstract

Background: Fosmanogepix (FMGX) inhibits glycosylphosphatidylinositol anchored cell wall transfer protein 1, essential for anchoring mannoproteins to fungal cell wall, critical for host invasion. This Phase 2 study evaluated efficacy and safety of FMGX treatment in invasive mold diseases (IMDs) by Aspergillus spp. and rare molds in adults with limited treatment options.

Methods: Participants (≥18 years) received FMGX 1000 mg intravenously (IV; 3-hour infusion) twice on Day 1 followed by 600 mg IV or 800 mg oral (optional from Day 4) once a day for ≤42 days. Key endpoints were all-cause mortality (Day 42) and Data Review Committee (DRC)-assessed global response (end of study treatment), adjudicated as success (complete or partial response) or failure (stable disease or progression of disease or death).

Results: Of 21 participants enrolled (safety population), 20 were included in the modified Intent-to-Treat population (mean age: 61.9 years; females: 2 [10%]). Day-42 all-cause mortality was 25% (80% confidence interval [CI]: 12.7%-41.5%). DRC-assessed global response success rate was 40% (80% CI: 24.9%-56.7%). 258 adverse events (AEs) were reported (n = 21). 15 participants experienced 36 FMGX-related AEs, 2 had 3 serious AEs. Three participants (14.3%) discontinued study treatment due to FMGX-related AEs. Nine deaths (43%) were reported. One death was assessed as possibly related and unrelated to FMGX by the investigator and Data and Safety Monitoring Board, respectively.

Conclusions: Safety profile was acceptable in high-risk patients with limited treatment options, supporting development of FMGX for treating IMDs caused by Aspergillus and rare molds. Clinical Trials Registration. NCT04240886; EudraCT number: 2019-001386-33.

Keywords: Aspergillus; Fusarium; Mucorales; fosmanogepix (FMGX); invasive mold infections/diseases.

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Conflict of interest statement

Potential conflicts of interest. M. R. H. was an employee of Amplyx (now a Pfizer Inc subsidiary), and subsequently was a consultant for Pfizer. He was previously an employee of Pfizer and holds Pfizer stock. M. A. and A. J. are employees of Pfizer and hold Pfizer stock. M. T. and R. P. are stockholders and former employees of Pfizer. G. R. received grant support from Abbvie, Gilead, MSD, Pfizer, Sanofi-Aventis, and Shionogi, provided advisory and consultancy services to Abbvie, Gilead, MSD, and Pfizer, and served on the speakers bureau for Abbvie, Gilead, MSD, and Pfizer. S. H. was an employee of Amplyx (acquired by Pfizer), Pfizer, and holds Pfizer stock. O. A. C. reports grants or contracts from Amplyx, Basilea, Cidara, F2G, Gilead, MSD, Mundipharma, Pfizer, Scynexis; consulting fees from Amplyx, Cidara, Gilead, Pfizer, Scynexis; honoraria for lectures from Al-Jazeera Pharmaceuticals, Astellas, Gilead, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, MSD, Mylan, Pfizer, Shionogi; payment for expert testimony from Cidara; participation on a Data Safety Monitoring Board or Advisory Board from Cidara, Pulmocide, Shionogi. M. A. S. reports grants from Gilead, Merck and F2G, as well as honoraria from Pfizer, Merck, Takeda and Gilead, and is on the DSMB/advisory boards for Pfizer, F2G, Mundipharma, Merck and Roche with all payments to an institution. S. S. D, reports grants from Merck, Ansun Biopharma, F2G, Allovir, Karius to the institution, consultant and served in advisory board for Takeda, Allovir, Merck, Aseptiscope, Inc, and honoraria for speakers bureau of Merck, Astellas, Takeda, and Karius. G. R. T. has received research and consulting support from Astellas, Cidara, F2G, Melinta, Mundipharma, Mayne and Merck, and has served on the Data Review Committee (DRC) for Pfizer. J. A. M. reports grants and personal fees from Bio-Rad, personal fees, and non-financial support from F2G, Mundipharma, Takeda, Astellas and Basilea, and grants, personal fees, and non-financial support from Gilead Sciences, Merck Sharp and Dohme, and Pfizer, Inc during the conduct of the study. O. A. C., M. A. S., and G. R. T. were also the members of the DRC for this study. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Graphical Abstract
Graphical Abstract
Fosmanogepix for the Treatment of Invasive Mold Diseases Caused by Aspergillus Species and Rare Molds: A Phase 2, Open-Label Study (AEGIS). This graphical abstract is also available at Tidbit: https://tidbitapp.io/institutional-portal/clinical-infectious-diseases/tidbits/fosmanogepix-for-the-treatment-of-invasive-mold-diseases-caused-by-aspergillus-species-and-rare-molds-a-phase-2-open-label-study-aegis/update
Figure 1.
Figure 1.
Study design. aPer DRC assessment, 1 participant was excluded from the mITT population due to not meeting the eligibility criteria. bFor the 12 participants where the fungal pathogen could not be identified, evidence for probable IMD was based on other diagnostic measures meeting the protocol adapted EORTC/MSGERC criteria, eg, galactomannan antigen (serum, plasma, or BAL) ELISA or Aspergillus PCR. Abbreviations: BAL, bronchoalveolar lavage; BID, twice daily; D, day; DNA, deoxyribonucleic acid; DRC, Data Review Committee; EORTC/MSGERC, European Organization for Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium; EOST, end of study treatment; ET, early termination; FMGX, fosmanogepix; IMD, invasive mold disease; IV, intravenous; mITT, modified intent-to-treat; PK, pharmacokinetics; QD, once daily.
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References

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