Safety and tolerability of inhaled molgramostim in autoimmune pulmonary alveolar proteinosis (aPAP)

ABSTRACT

Background: aPAP is a rare lung disease characterized by surfactant build-up for which there is no approved pharmacologic treatment. aPAP patients typically present with shortness of breath due to impaired oxygen transfer in the lung . Objective(s) To report the long-term safety of inhaled molgramostim nebulizer solution (MOL) administered intermittently in aPAP patients open-label IMPALA-X extension study (NCT03482752). Method(s) Patients who completed IMPALA (NCT02702180) were eligible for IMPALA-X. MOL (300 mug;once daily) was administered in cycles of 7 days on/7 days off treatment. The primary endpoint included adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), and discontinuations. Result(s) Safety data from 59 patients were analyzed;44 (74.6%) and 15 (25.4%) patients had >=12 and >=24 months of exposure, respectively. Forty (67.8%) patients reported 165 AEs;138 AEs in 38 (64.4%) patients were treatmentemergent AEs (TEAEs). Eight patients had SAEs that were considered unlikely related to treatment. Seven patients had severe TEAEs and 3 were considered treatment-related/ADRs. Most common AEs (7 patients each, 11.9%) were cough and nasopharyngitis. Respiratory tract infection, arthralgia, alveolar proteinosis, and COVID-19 were each reported by 6.8% patients. No TEAEs led to treatment discontinuation/withdrawal. One subject died following COVID-19 infection 24 days after the last MOL dose. Conclusion(s) IMPALA-X was discontinued early as intermittent dosing did not show a benefit vs placebo in the IMPALA study. The phase 3 IMPALA-2 study of continuous daily MOL vs placebo in patients with aPAP is ongoing.