RCT Abstract - Inhaled molgramostim improves pulmonary gas exchange and respiratory health-related quality of life (HRQoL) in patients with autoimmune pulmonary alveolar proteinosis (aPAP): Results from IMPALA-2

<bold>Background:</bold> aPAP is a rare lung disease caused by autoantibodies to granulocyte–macrophage colony-stimulating factor (GM-CSF) characterized by alveolar surfactant accumulation, which results in impaired oxygen delivery to blood. <bold>Objective:</bold> To investigate the efficacy and safety of molgramostim (recombinant GM-CSF) in aPAP patients. <bold>Methods:</bold> IMPALA-2 is a global, randomized, double-blind, placebo-controlled Phase 3 trial of inhaled molgramostim in adult aPAP patients receiving nebulized molgramostim 300 µg or placebo once daily for 48 weeks (wks). The primary endpoint was mean change from baseline in the diffusing capacity of the lungs for carbon monoxide expressed as % predicted adjusted for hemoglobin (DLco%) at wk 24. Secondary endpoints included mean changes from baseline in DLco% at wk 48 and St. George’s Respiratory Questionnaire (SGRQ) total score at wks 24 and 48. <bold>Results:</bold> Study participants (n=164) received molgramostim (n=81) or placebo (n=83). Molgramostim significantly improved DLco% compared with placebo at wk 24 (difference in least squares mean change 6.0%; p=0.0007) and wk 48 (6.9%; 95% CI 2.9, 10.9). Molgramostim patients had greater mean improvements in SGRQ total score than placebo patients at wk 24 (−6.59; 95% CI -11.4, -1.79) and at wk 48 (−4.87; 95% CI -10.76, 1.01). Results for other secondary endpoints were also positive. Molgramostim was well-tolerated; only 2 adverse events led to discontinuation of molgramostim. <bold>Conclusions:</bold> Molgramostim was well tolerated and significantly improved pulmonary gas exchange and respiratory HRQoL in aPAP patients.