N Engl J Med

Inhaled GM-CSF agonist improves outcomes in autoimmune pulmonary alveolar proteinosis

August 22, 2025

Study details: The IMPALA-2 trial (NCT04544293) was a global, randomized, double-blind, placebo-controlled phase 3 study evaluating inhaled molgramostim (300 µg daily) in 164 adults with autoimmune pulmonary alveolar proteinosis (aPAP) across 43 sites in 16 countries. Primary endpoint was change in hemoglobin-adjusted percent predicted DLco% at week 24, with secondary endpoints including DLco% at Week 48, St. George’s Respiratory Questionnaire (SGRQ) scores, exercise capacity (METs), and surfactant burden (GGO score).

Results: Molgramostim significantly improved DLco% at week 24 (9.8% vs. 3.8%; p<0.001) and week 48 (11.6% vs. 4.7%; p<0.001). SGRQ Total and Activity scores showed clinically meaningful reductions, and exercise capacity improved by 0.6 METs at week 48. Surfactant burden (GGO score) decreased more in the treatment group, and fewer patients required whole lung lavage. The drug was well tolerated, with most adverse events mild or moderate.

Clinical impact: Molgramostim offers a targeted, inhaled therapy that addresses the underlying pathophysiology of aPAP, improving gas exchange, symptoms, and functional status, and may reduce the need for invasive lavage procedures.

Source:

Trapnell BC, et al; IMPALA-2 Trial Investigators. (2025, August 20). N Engl J Med. Phase 3 Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis. https://pubmed.ncbi.nlm.nih.gov/40834301/