Efficacy of inhaled molgramostim according to severity of autoimmune pulmonary alveolar proteinosis (aPAP)

<bold>Background:</bold> The IMPALA-2 Phase 3 clinical trial showed that molgramostim inhalation solution (MOL), an investigational recombinant granulocyte-macrophage colony stimulating factor, led to greater mean improvements in pulmonary gas transfer, respiratory health-related quality of life, exercise capacity, and surfactant burden, compared with placebo (PBO). <bold>Objective:</bold> To determine the efficacy of MOL in aPAP patients based on their disease severity at baseline. <bold>Methods:</bold> In IMPALA-2, aPAP patients received MOL 300 µg or PBO once daily for 48 weeks (wks). The primary endpoint was change from baseline in diffusing capacity of the lungs for carbon monoxide expressed as % predicted adjusted for hemoglobin (DLco%) at wk 24. Secondary endpoints included changes from baseline in DLco% at wk 48, and St. George’s Respiratory Questionnaire Total/Activity scores and exercise capacity (peak metabolic equivalents) at wks 24 and 48. Prespecified analyses were conducted on primary and secondary endpoints in subgroups of patients with DLco% values ≤50% (MOL, n=31; PBO, n=32) or >50% (MOL, n=50; PBO, n=51) at randomization. <bold>Results:</bold> MOL improved DLco% compared to PBO at wk 24 in both subgroups of patients with DLco% values ≤50% (treatment difference by comparison of least squares mean changes from baseline [LSM] 5.6%; 95% confidence interval [CI], 0.0, 11.3) and those with baseline DLco% values >50% (treatment difference 6.2; 95% CI, 1.7, 10.6). Subgroup results for secondary endpoints were comparable with those for the total population. <bold>Conclusions:</bold> MOL was effective in aPAP patients regardless of disease severity based on DLco%.