Molgramostim (DB12525): A Comprehensive Monograph on a Novel Inhaled Therapy for Autoimmune Pulmonary Alveolar Proteinosis

Executive Summary

Molgramostim is an investigational biotech therapeutic poised to address a significant unmet medical need in the treatment of autoimmune Pulmonary Alveolar Proteinosis (aPAP), a rare and debilitating lung disease. Developed by Savara Pharmaceuticals, Molgramostim is a recombinant, non-glycosylated form of human granulocyte-macrophage colony-stimulating factor (GM-CSF) formulated as an inhaled solution. Its mechanism of action directly targets the underlying pathophysiology of aPAP by restoring the function of alveolar macrophages, which are impaired by autoantibodies against endogenous GM-CSF. This targeted replacement therapy reactivates the natural clearance of lung surfactant, thereby improving pulmonary gas exchange.

The clinical development program has culminated in the pivotal Phase 3 IMPALA-2 trial, which demonstrated compelling and statistically significant efficacy across multiple domains. Treatment with inhaled Molgramostim resulted in marked improvements in pulmonary gas transfer, a key physiological measure of lung function. These objective gains were complemented by clinically meaningful enhancements in respiratory health-related quality of life and functional exercise capacity, directly linking the drug's physiological effect to tangible patient benefits. Furthermore, the therapy reduced the underlying surfactant burden in the lungs and decreased the need for whole lung lavage, the current invasive standard of care.