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

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. 3 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.

Conclusion: 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.

Trial registration: NCT04240886; EudraCT number: 2019-001386-33.

Keywords: Aspergillus; Fusarium; Fosmanogepix (FMGX); Invasive mold infections/diseases; Mucorales; all-cause mortality.