Recombinant GM-CSF drug evaluation review.

Autoimmune Pulmonary Alveolar Proteinosis (aPAP) is a rare disease characterized by myeloid cell dysfunction, abnormal pulmonary surfactant accumulation, and innate immune deficiency. Pathogenesis is driven by GM-CSF neutralizing autoantibodies (GMAbs) present in high titer in serum and bronchoalveolar lavage fluid (BALF) of patients. GM-CSF is a cytokine and a hematopoietic growth factor produced by a variety of cells. In the lungs, GM-CSF regulates surfactant homeostasis and lung host defense through innate immune function. Whole lung lavage (WLL) is the current first line therapy for aPAP. It is a procedure in which excessive surfactant is mechanically removed from the alveoli. Pathogenesis-driven treatment with GM-CSF augmentation has been investigated over the last two decades with recombinant GM-CSF (rGM-CSF). Molgramostim and sargramostim are rGM-CSF which can be self-administered at home by patients with aPAP either subcutaneously or using a handheld nebulizer. In Phase II and III studies of adults with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. In all clinical studies to date, rGM-CSF has shown a favorable safety profile with no dose limiting toxicity. This supports the application of inhaled rGM-CSF for the treatment of aPAP and the possibility of WLL as a rescue therapy.