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

Abstract

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. 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). 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. 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.