Savara reported new Phase 3 IMPALA-2 biomarker data showing molgramostim improved pulmonary gas transfer and reduced disease severity biomarkers in autoimmune PAP patients.
Written By: Fariha Sameen, PharmD
Reviewed By: Pharmacally Editorial Team
Savara Inc. presented new biomarker data from the Phase 3 IMPALA-2 trial (NCT04544293) showing that nebulized molgramostim improved pulmonary gas transfer and reduced multiple biomarkers associated with disease severity in patients with autoimmune pulmonary alveolar proteinosis (aPAP). The findings were presented at the 2026 ATS International Conference in Orlando.
aPAP is a rare autoimmune lung disease caused by antibodies that neutralize granulocyte-macrophage colony-stimulating factor (GM-CSF), impairing alveolar macrophage function and preventing normal surfactant clearance from the lungs. The resulting surfactant accumulation disrupts oxygen exchange and can lead to progressive respiratory decline, pulmonary fibrosis, and lung transplantation in severe cases. Molgramostim replaces GM-CSF locally in the lungs, directly targeting the underlying disease mechanism.
The double-blind, placebo-controlled global study evaluated inhaled molgramostim 300 µg once daily in 164 patients with aPAP over 48 weeks. Patients received either molgramostim (n=81) or placebo (n=83). Investigators assessed several serum biomarkers, including KL-6, CYFRA 21-1, lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), hemoglobin, and hematocrit.
Molgramostim significantly improved diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLco%) versus placebo at both Week 24 (P=0.0007) and Week 48 (P=0.0008). Post-hoc analyses also showed significantly greater reductions in LDH, CYFRA 21-1, and KL-6 in the treatment arm compared with placebo across both timepoints.
Among the key findings, reductions in biomarker levels closely correlated with improvements in pulmonary gas transfer. Investigators reported strong negative correlations between DLco% improvement and decreases in KL-6, CYFRA 21-1, and LDH, with all correlations reaching P<0.0001. Hemoglobin, hematocrit, and CEA levels remained similar between treatment groups throughout the study.
The findings provide additional mechanistic support for molgramostim’s clinical activity by linking biomarker reductions with restoration of lung function. The ATS presentation further strengthens evidence supporting inhaled GM-CSF replacement as a targeted therapeutic strategy for aPAP, a disease with limited approved treatment options and substantial unmet need.
The abstract has been published in a supplement of the American Journal of Respiratory and Critical Care Medicine (AJRCCM), while the full poster will be available through Savara’s congress publications portal.
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About the Writer
Fariha Sameen, PharmD (LinkedIn), is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.